kapitel2a
TRANSCRIPT
BASF Pharma Ingredients Generic Drug Formulations 2005
2 Tablets obtainedby direct compression
2.1 Size of formulations
The formulations were developed ona laboratory scale in which case200 –1,000 g of the mixtures to be tabletted were used. Normally, theamounts weighed out in the formula-tions correspond to the amount in thetablets multiplied by a factor of 1,000.
2.2 Direct compression
The technology involved in directcompression assumes great impor-tance in the tablet formulations, be-cause it is often the cheapest means,particularly in the production of ge-nerics, that the active substance per-mits. The limiting factors are thephysical properties of the active sub-stance and its concentration in thetablets (cf. Chapter 2.4). Even sub-stances such as ascorbic acid thatare hardly suitable for direct compres-sion, owing to the friability of theircrystals, can normally be directlypressed into tablets at concentrationsof 30 – 40 %. However, this techniqueis not as suitable if the content of as-corbic acid is higher. This limit may beshifted upwards by special directcompression auxiliaries, e.g. Ludi-press. Two important alternatives, viz.Ludipress grades and Kollidon VA 64,can be found in the BASF line ofpharmaceutical excipients for directcompression.
A. Ludipress grades
Ludipress is a speciality derived fromlactose, Kollidon 30, and Kollidon CL.It thus combines the properties of afiller, binder, disintegrant, and flowagent and also often acts as a releaseaccelerator. By virtue of its versatility,formulations containing it are usuallyvery simple. It can also be combinedwith almost all active substances withthe exception of those that enter intoa chemical interaction with lactose(Maillard reaction).
Active substances, e.g. many anal-getics, behave very differently withLudipress when the dosage is ex-tremely high. Acetylsalicylic acid andmetamizole can be pressed when little Ludipress has been added; ibuprofen requires a larger amount;and the fraction of Ludipress requiredin the tablets is too large for para-cetamol (= acetaminophen).
B. Kollidon VA 64
An alternative to the Ludipress gradesis the outstanding dry binder KollidonVA 64 together with excipients, e.g.calcium phosphate, microcrystallinecellulose, lactose, or starch, and adisintegrant, e.g. Kollidon CL. Thiscombination even allows 500 mg ofparacetamol to be pressed into goodtablets with a weight of 700 mg.
No other dry binder has a bindingpower and plasticity comparable tothose of Kollidon VA 64. Plasticity, inparticular, is an important parameterin direct compression. As can beseen in Fig. 1, this property of Kolli-don VA 64 is not adversely effectedby increasing the pressure. The bene-ficial properties of Kollidon VA 64 can
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BASF Pharma Ingredients Generic Drug Formulations 2005
also be exploited for the productionof concentrated active substance thatis subsequently used for direct tablet-ting.
Obviously, Kollidon VA 64 and Ludi-press can also be combined with oneanother.
2.3 Tablet press
All the formulations were devised onrotary tabletting presses that were fitted with 10 – 20 punches.
2.4 Effect of the physical prop-erties of the active substance
In the manufacture of tablets it isimportant to define and appreciatethe physical properties of the activesubstance. This particularly concernsthe particle size and the flowability.
Fig. 2 shows the difference that canoccur when ascorbic acid tablets ofthe same composition are producedat the same pressure, but when theactive substance consists of crystalsof two different sizes (crystalline = > 150 µm; powder = < 150 µm).
2.5 Effect of the physical properties of the excipients
Characterization of the physical prop-erties of excipients is also importantbecause the influences can be similaras mentioned for active ingredients.
2.6 Methods of measuring theproperties of tablets
The general instructions for the deter-mination of the corresponding proper-ties of tablets (hardness, disintegra-tion, friability, dissolution) are con-tained the Pharmacopoeiae Ph.Eur. orUSP. If it is not stated to the contrary,the disintegration time is measured in
Fig. 1 Plasticity of dry binders in tablets(99.5 % binder + 0.5 % magnesium stearate)
1.0
0.9
0.8
0.7
0.6
0.4
0.5
Kollidon VA 64 Kollidon 30 Mc. Cellulose HPMC 11000
Pla
stic
ity
Plasticity = plastic energy/total energy
Force: 18 kN
Force: 25 kN
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artificial gastric juice. The dissolutionis determined by the conditions laiddown in the corresponding mono-graphs for the tablets (usually USP)and in the prescribed medium.
2.7 Information on dissolution ofactive substance
Nowadays it is standard practiceand/or laid down that the in-vitro release of active substance bechecked. Unfortunately, these datacannot be given for all formulations.This is particularly the case when theactive substance is sufficiently solubleor when the formulation was devel-oped in a time when this parameterwas not yet demanded.
2.8 Formulations
The formulations in this chapter havebeen arranged in the alphabetic orderof their active substances.
140
120
100
80
40
60
crystalline gradeCompression force: 25 kN
powder grade
Tabl
et H
ardn
ess
(N)
Fig. 2 Direct compression of different types of ascorbic acid(40 % ascorbic acid, 5 % Kollidon VA 64)
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Acetylcysteine Effervescent Tablets (600 mg)
Formulation
Acetylcysteine, crystalline (Merck).............600 gLudipress LCE [1] ....................................400 gSodium bicarbonate ................................450 gTartaric acid, powder ...............................350 gPolyethylene glycol 6000, powder [6]..........75 gApartame (Searle) ......................................25 gOrange flavour (Dragoco) ............................q.s.
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with medium com-pression force at a maximum of 30 % of relative atmospheric humidity.
3. Tablet properties
Weight................................................1975 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................97 NDisintegration......................................2 – 3 minFriability ...................................................1.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Acetylsalicylic Acid + Paracetamol (= Acetaminophen) + Caffeine Tablets (400 mg + 100 mg + 30 mg)
Formulation
Acetylsalicylic acid, crystalline ..................400 gParacetamol, crystalline (BASF) ................100 gCaffeine (BASF) .........................................30 gLudipress [1] ...........................................100 gKollidon CL [1] ..........................................20 gPolyethylene glycol 6000, powder [6]..........30 gStearic acid [7] ............................................5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with low compres-sion force.
3. Tablet properties
Weight .................................................683 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................116 NDisintegration......................................1 – 2 minFriability...................................................0.3 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Acetylsalicylic Acid-Acetaminophen-Caffeine-Tablet (250 mg +250 mg+ 50 mg)
Formulation
Acetaminophen powder ........................250.0 gCaffeine powder .....................................50.0 gASS powder .........................................250.0 gKollidon® VA 64 ....................................60.0 g
b) Manufacture by Roller Compaction
The active ingredients and Kollidon® VA 64 were granulated in a Gerteis Roller compactor.
Process parameters
Force ...............................................5.0 kN/cmCrack...................................................2.9 mmLooser .................................................5.0 rpmDosing srew .......................................90.5 rpmPlug screw .......................................108.6 rpmGranulator.............................................50 rpm
c) Formulation of the tablets
Acetaminophen powder .....................250.0 mgCaffeine powder ..................................50.0 mgASS powder ......................................250.0 mgKollidon® VA 64 ..................................60.0 mgKollidon® CL.......................................20.0 mgAerosil 200 ............................................3.0 mgMagnesium stearate [8] ..........................4.0 mg
BASF Pharma Ingredients Generic Drug Formulations 2004
2. Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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d) Tableting
The granules were passed together with magnesium stearate, Aerosil® 200 and Kollidon® CL through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a forceof about 12kN.
Tablet press ..................Korsch PH106, 30 rpmCompression force ................................11.5kN
e) Tablet properties
Weight ...............................................629.7mgS rel ........................................................1.4 %Diameter ................................................12mmForm ...................................................biplanarHardness...................................................72NFriability.................................................2,75 %
f) Dissolution
BASF Pharma Ingredients Generic Drug Formulations 2005
Acetylsalicylic Acid-Acetaminophen Caffeine-Tablet (250 mg +250 mg+ 50 mg) page 2
0
20
40
60
80
100
120
0 20 40 60 80 100 120 140
time [min]
dru
g r
elea
se [
%]
BASF
Melabon
method: paddle 50 rpm; 37°Cdeionized water
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g Content uniformity
BASF Pharma Ingredients Generic Drug Formulations 2004
Acetylsalicylic Acid-Acetaminophen Caffeine-Tablet (250 mg +250 mg+ 50 mg) page 3
175,00
200,00
225,00
250,00
275,00
300,00
325,00
0 1 2 3 4 5 6 7 8 9 10
number of tablets
con
ten
t / 1
00m
g t
able
t [m
g]
70
80
90
100
110
120
130
rele
ase
dru
g[%
]
assay
experial content
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Acetylsalicylic Acid + Paracetamol (= Acetaminophen) Tablets(250 mg + 250 mg)
Formulation
Acetylsalicylic acid, crystalline (Merck) ......250 gParacetamol, crystalline (BASF) ................250 gAvicel PH 101 [5] .......................................60 gKollidon 30 (or Kollidon VA 64) [1] ...............15 gKollidon CL [1] ..........................................25 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press withmedium compression force.
3. Tablet properties
Weight .................................................605 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration .......................................< 1 minFriability...................................................0.7%
4. Chemical stability of formulation No. 2 (20–25 °C, closed)
0 Months 6 Months 12 Months
Acetylsalicylic acid 100 % 100 % 100 %Vitamin C 100 % 100 % 96 %Free acetic acid < 0,01% < 0.01%Free salicylic acid < 0,01% < 0.01%
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2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Acetylsalicylic Acid + Vitamin C Effervescent Tablets (400 mg + 250 mg)
1. Formulations
No. 1 No. 2
Acetylsalicylic acid (Synopharm) ....................400 g 400 gAscorbic acid, crystalline (BASF) ...................250 g 250 gLudipress LCE [1] .........................................600 g 500 gCtitric acid, crystalline ..................................300 g 400 gSodium bicarbonate .....................................600 g 600 gLutrol E4000F [1]............................................90 g 90 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with highcompression force.
3. Tablet properties
No. 1 No. 2
Weight ....................................................2251 mg 2244 gDiameter ....................................................20 mm 20 mmForm ........................................................biplanar biplanarHardness.....................................................145 N 125 NDisintegration ....................................1 min 35 sec 1 min 22 secFriability .....................................................0.66 % 0.86 %Colour ..........................................................white white
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg)
1. Formulations
No. 1 No. 2
Acetylsalicylic acid, crystalline (Merck) ...........325 g 325 gAscorbic acid, powder (BASF).......................250 g 250 gSorbitol, crystalline [10] .................................120 g –Avicel PH 101 [5] ............................................40 g 100 gKollidon VA 64 [1] ...........................................25 g 12 gKollidon CL [1] ...............................................20 g 30 gMagnesium stearate [2] ....................................2 g 3 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press withmedium/high compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................790 mg 726 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................92 N 100 NDisintegration ...............................................2 min < 1 minFriability ..........................................................1% 1%
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4. Chemical stability of formulation No. 2 (20–25 °C)
0 Months 6 Months 12 Months
Acetylsalicylic acid 100 % 100 % 100 %Vitamin C 100 % 100 % 96 %Free acetic acid < 0,01% < 0.01%Free salicylic acid < 0,01% < 0.01%
BASF Pharma Ingredients Generic Drug Formulations 2005
Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg) page 2
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Acetylsalicylic Acid + Vitamin C Tablets(400 mg + 250 mg)
1. Formulation
Acetylsalicylic acid, crystalline (Merck) ......400 gAscorbic acid, powder (BASF) ..................250 gLudipress [1] ...........................................100 gKollidon CL [1] ..........................................20 gMacrogol 6000 powder [6] ...........................3 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press withmedium compression force.
3. Tablet properties
Weight .................................................841 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................120 NDisintegration ........................................<1 minFriability...................................................0.4 %Free acetic acid ...................................<0.01%Free salicylic acid .....................................0.1%Colour .....................................................white
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Stability after 12 months (20–25 °C, closed)
Hardness ................................................130 NDisintegration ........................................<1 minFriability...................................................0.8 %Acetylsalicylic acid ..................................100 %Ascorbic acid ..........................................100 %Free acetic acid ...................................<0.01%Free salicylic acid .....................................0.1%Colour of the tablets .................................white
BASF Pharma Ingredients Generic Drug Formulations 2005
Acetylsalicylic Acid + Vitamin C Tablets (400 mg + 250 mg) page 2
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Acetylsalicylic Acid Tablets (400 mg)
1. Formulation
Acetylsalicylic acid, crystalline (Merck) ......400 gLudipress [1] .............................................99 gStearic acid [7] ............................................1 gKollidon CL [1]...........................................15 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................516 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration ........................................<1 minFriability...................................................0.4 %Dissolution, 15 min....................................84 %
30 min ...................................97%
4. Chemical stability
Storage time RT 40 °C
0 months 100.0 % 100.0 %6 months 100.0 % 100.0 %
12 months 98.4 % 100.0 %
The content of free salicylic acid remained always below 0.2 %.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Acetylsalicylic Acid Tablets (500 mg)
1. Formulation
Acetylsalicylic acid (Merck) .......................500 gAvicel PH 101 [5] .....................................200 gKollidon 30 [1] ...........................................15 gKollidon CL [1] ..........................................25 gMagnesium stearate [2] ...............................3 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force.
3. Tablet properties
Weight .................................................707 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................61 NDisintegration ........................................<1 minFriability...................................................0.7%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Albendazole Tablets,(100 mg)
1. Formulation
Albendazole ............................................100 gLudipress [1] ...........................................288 gMagnesium stearate [2] ...............................4 gAerosil 200 [4] .............................................8 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................400 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................99 NDisintegration ..........................................2 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Alginic Acid + Aluminium Hydroxide + Magnesium Silicate Tablets (500 mg + 100 mg + 25 mg)
1. Formulation
Alginic acid .............................................500 gAluminium hydroxide dried gel (Giulini) ......100 gMagnesium trisilicate .................................25 gSodium bicarbonate.................................170 gSorbitol, crystalline [10] ............................160 gSucrose, crystalline .................................627 gLudipress [1] ...........................................900 gKollidon VA 64 [1] ......................................70 gMagnesium stearate [2]..............................50 gVanillin ........................................................5 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with high compression force.
3. Tablet properties
Weight ...................................................2.55 gDiameter ...............................................20 mmForm ...................................................biplanarHardness ................................................120 NFriability...................................................1.3 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Alpha-Methyldopa Tablet Cores (250 mg), DC
1. Formulation
Alpha-Methyldopa ...................................250 gLudipress [1] ...........................................350 gStearic acid [7] ..........................................15 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................620 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness ................................................123 NDisintegration ..........................................6 minFriability...................................................0.2 %Dissolution (10 min) ...................................91%
(20 min)...................................98 %
4. Physical stability (20 months, 20–25 ºC)
Weight .................................................620 mgHardness ................................................115 NDisintegration ..........................................7 minFriability...................................................0.5 %Dissolution (10 min) ...................................91%
(20 min) .................................100 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Alpha-Methyldopa Tablets (500 mg), DC
1. Formulations
No. 1 No. 2
Alpha-Methyldopa .......................................500 g 500 g(Alpha Chemicals)Avicel PH 101 [5] ............................................54 g 200 gKollidon VA 64 [1] ...........................................20 g 30 gKollidon CL [1] ...............................................20 g 20 gTalc [10] .........................................................90 g 8 gAerosil 200 [4]..................................................7 g 1 gMagnesium stearate [2] ....................................2 g –Calcium arachinate [2] .........................................– 1 g
2. Manufacturing (Direct compression)
Pass magnesium stearate trough a 0.2 mm sieve and the other compo-nents through a 0.5 mm sieve, mix and press with high compressionforce (Formulation No. 1) and low compression force (Formulation No. 2).
3. Tablet properties
No. 1 No. 2
Weight ..........................................693 mg 750 mgDiameter ...........................................12 mm 12 mmForm ..........................................biplanar biplanarHardness ..............................................80 N 113 NDisintegration ...........................................<1 min 1 – 2 minFriability .............................................0.4 % 0.8 %Dissolution, 4 min ........................................86 % –
16 min ......................................92 % –
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Remark
In the case of formulation No. 1 it was not possible to press tablet coresof a biconvex form because some capping effect was observed.
BASF Pharma Ingredients Generic Drug Formulations 2005
Alpha-Methyldopa Tablets (500 mg), DC page 2
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Alprazolam Tablets (0.5 mg)
1. Formulation
Alprazolam...............................................0.5 gLudipress [1] ...........................................148 gMagnesium stearate [2] ...............................1 g
2. Manufacturing (Direct compression)
Mix all components, sieve through a 0.8 mm screen and press with low compression force.
3. Tablet properties
Weight .................................................158 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................106 NDisintegration ..........................................3 minFriability .................................................<0.1%
4. Remark
If the content uniformity does not meet the requirements it would berecommended to prepare a premix of the active ingredient with a smallpart of the Ludipress or with lactose monohydrate before mixing with theother components of the formulation.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Aluminium Hydroxide + Magnesium SilicateChewable Tablets (120 mg + 250 mg)
1. Formulation
Aluminium hydroxide dried gel (Giulini) ...120.0 gMagnesium trisilicate ............................250.0 gLudipress [1] ........................................232.0 gAerosil 200 [4] ..........................................6.0 gMagnesium stearate [2].............................6.0 gCyclamate sodium ..................................12.0 gMenthol ...................................................1.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with a compression force of 20 kN.
3. Tablet properties
Weight .................................................640 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................83 N
4. Remarks
Due to the poor flowability of the powder the tabletting machine shouldbe equipped with a special technical device providing a continuous andhomogenous filling of the dies.
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ambroxol Tablets (30 mg)
1. Formulation
Ambroxol hydrochloride ..........................30.0 gLudipress [1] .........................................217.5 gMagnesium stearate [2].............................2.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................250 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................115 NDisintegration ..........................................7 minFriability...................................................0.2 %Dissolution, 30 min ...................................82 %
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2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ambroxol HCl Sustained-Release PelletsReleasing Tablets (MUPS-Formulation)
d) Formulation
The formulation is designed for 500g of tablets:
Ambroxol HCl/ Kollicoat® SR 30D pellets* ...250.0gMicrocrystalline cellulose Vivapur® 200 [7] ........................................250.0gMagnesium stearate [8] ..................................2.5g
e) Procedure
Mix the ingredients together, pass through a 0.8mm sieve and compressinto tablets with a force of about 15kN.
Tablet press ................Korsch EK0, 30 tablets/ minCompression force ........................................15kN
f) Tablet properties
Weight .......................................................400mgDiameter .....................................................10mmForm ........................................................biplanarHardness .................................................92-116N
* The pellets are manufactured using the spary suspension described in chapter 4.5.3 underAmbroxol HCI Substained-release pellets (drug-layering process)
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulation of tablets obtained by Direct Compression (Lab Scale)
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Ambroxol HCl Sustained-Release Pellets Releasing Tablets page 2
0
20
40
60
80
100
0 4 8 12 16 20
time [h]
dru
g r
elea
se [
%]
5% Kollicoat SR 30D
10% Kollicoat SR 30D
15% Kollicoat SR 30D
20% Kollicoat SR 30D
method: paddle 100 rpm; 37°C0-20h: pH 7.4
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Aminophylline Tablets (100 mg), DC
1. Formulations
No. 1 No. 2
Aminophylline powder (BASF)........................100 g 100 gLudipress [1] ................................................150 g –Avicel PH 200 [5].................................................– 200 gKollidon VA 64 [1] ................................................– 6 gMagnesium stearate [2] ....................................2 g 2 gAerosil 200 [4]..................................................2 g 12 g
2. Manufacturing (Direct compression)
Mix all components, sieve and press on a rotary press to tablets with lowcompression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................254 mg 318 mgDiameter ......................................................8 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................97 N 124 NDisintegration .............................................10 min 1 – 2 minFriability .......................................................0.2 % 0.2 %Dissolution 10 min:........................................87% –
15 min: ......................................100 % –
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4. Colour stability of Formulation No. 1
After 2 weeks at room temperature no change of the colour of thetablets was observed but the long term compatibility between amino-phylline and lactose should be controlled.
5. Remark for Formulation No. 2
Due to the reduced flowability the tabletting machine should be equippedwith a special technical device providing a continuous and homogenousfilling of the molds.
BASF Pharma Ingredients Generic Drug Formulations 2005
Aminophylline Tablets (100 mg) page 2
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Amitryptylline Tablets (10 mg and 25 mg)
1. Formulations
No. 1: No. 2:10 mg 25 mg
Amitryptylline...............................................10 mg 25 mgLudipress [1] .............................................139 mg 124 mgMagnesium stearate [2] ....................................1 g 1 mg
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix intensively and presswith low compaction force (8 kN).
3. Tablet properties
No. 1 No. 2
Weight ......................................................152 mg 157 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................70 N 92 NDisintegration...........................................1 – 2 min 3 minFriability .......................................................0.3 % 0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ampicillin Tablets(250 mg)
1. Formulation
Ampicillin trihydrate .................................250 gLudipress [1] ...........................................250 gMagnesium stearate [2] ..............................10 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with low compres-sion force.
3. Tablet properties
Weight .................................................500 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................84 NDisintegration ..........................................4 minFriability...................................................0.4 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Asparagus Extract + Parsley Extract Tablets (200 mg + 200 mg)
1. Formulation
Asparagus extract, powder ......................200 gParsley extract, powder ...........................200 gSorbitol, crystalline [10] ............................200 gKollidon VA 64 [1] ......................................20 gKollidon CL [1]...........................................10 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force.
3. Tablet properties
Weight .................................................636 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................49 NDisintegration ..........................................9 minFriability .....................................................0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Aspartame Effervescent Tablets(20 mg)
1. Formulation
Aspartame .............................................20.0 gSorbitol, crystalline [10] ...........................10.4 gTartaric acid, powder ..............................14.3 gSodium bicarbonate................................18.7 gKollidon 25 [1] ..........................................1.7 gPolyethylene glycol 6000, powder [6] .........1.1 g
2. Manufacturing (Direct compression)
Mix , pass through a 0.5 mm sieve and press to tablets.
3. Tablet properties
Weight ...................................................66 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................25 NDisintegration ........................................<1 minFriability...................................................0.7%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Aspartame Tablets (25 mg), DC
1. Formulation
Aspartame ................................................27 gLudipress [1] .............................................76 gKollidon CL [1]...........................................12 gMagnesium stearate [2] ...............................1 gLutrol F 68 [1] .............................................3 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith low compression force.
3. Tablet properties
Weight .................................................120 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................65 NDisintegration ........................................<1 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Atenolol Tablets (90 mg)
1. Formulation
Atenolol (Stober).....................................93.0 gLudipress [1].........................................287.0 gKollidon CL [1]........................................52.0 gMagnesium stearate [2].............................2.2 gAerosil 200 [4] ..........................................0.9 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith low compression force.
3. Tablet properties
Weight .................................................436 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................85 NDisintegration......................................2 – 3 minFriability .................................................<0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Benzhexol Tablets (5 mg)
1. Formulations
No. 1 No. 2
Benzhexol chloride .......................................5.0 g 5.0 g(= trihexylphenidyl hydrochloride)Ludipress [1]..............................................114.0 g 100.0 gCorn starch [3] ....................................................– 14.5 gMagnesium stearate [2] .................................0.6 g 0.5 gAerosil 200 [4] .....................................................– 1.5 g
2. Manufacturing (Direct compression)
Mix all components for 10 minutes in a turbula mixer and press with low compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................120 mg 121 mgDiameter ......................................................5 mm 5 mmForm ........................................................biplanar biplanarHardness.....................................................120 N 113 NDisintegration ...............................................7 min 3 minFriability ...................................................< 0.06 % 0.4 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Berberine Tablets (5 mg)
1. Formulation
Berberine sulfate ......................................5.7 gLactose monohydrate [8].........................54.1 gLudipress [1] ..........................................54.1 gMagnesium stearate [2].............................1.2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight..................................................115 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................40 NDisintegration ..........................................1 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene + Vitamin C + Vitamin E Chewable Tablets(3 mg + 50 mg + 25 mg)
1. Formulations
No. 1 No. 2
Betavit® Dry Powder 10 % (BASF....................30 g 30 gAscorbic acid, powder (BASF).........................50 g 50 gDry Vitamin E acetate 50 % DC (BASF) ............50 g 50 gLudipress LCE [1] .........................................365 g –Sorbitol, cryst. [10] ..............................................– 335 gKollidon VA64 [1].................................................– 30 gMagnesium stearate [2] ....................................5 g 5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with high compres-sion force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................503 mg 506 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness.....................................................126 N 167 NDisintegration (water)...................................17 min 8 minFriability........................................................0.1% 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene + Vitamin C + Vitamin E Chewable Tablets(10 mg + 500 mg + 250 mg)
1. Formulation
Beta Carotene dry powder 10 % ...............100 gAscorbic acid, crystalline (BASF) ..............250 gSodium ascorbate, crystalline...................280 gVitamin E acetate dry powder SD 50 ........500 g(BASF)Sorbitol, crystalline [10] ............................600 gLudipress [1] ...........................................500 gFructose .................................................350 gPolyethylene glycol 6000, powder [6]..........50 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with high compres-sion force.
3. Tablet properties
Weight ..............................................2,600 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness ................................................122 NDisintegration (water) .......................15 – 20 minFriability...................................................0.4 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene + Vitamin C + Vitamin EEffervescent Tablets(12 mg + 150 mg + 25 mg)
1. Formulation
Lucarotene Dry Powder 10 % CWD G/Y (BASF) .....................................120 gAscorbic acid, crystalline (BASF) ..............150 gDry Vitamin E acetate 50 % DC (BASF) .......50 gLudipress LCE [1] ....................................705 gKollidon VA64 [1] .......................................50 gCitric acid, anhydrous ..............................450 gSodium bicarbonate ................................320 gPolyethylene glycol 6000, powder [10] ........75 gOrange flavour (Dragoco) ...........................50 gAspartame (Searle) ....................................30 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with high compres-sion force at a maximum of 30 % of relative atmospheric humidity.
3. Tablet properties
Weight ...............................................2045 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................95 NDisintegration (water) ...............................3 minFriability...................................................0.9 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene + Vitamin C + Vitamin E Tablets(6 mg + 100 mg + 30 mg)
1. Formulations
No. 1 No. 2
Betavit® dry powder 10 % (BASF) ...................65 g 65 gAscorbic acid, powder (BASF) .......................100 g 100 gVitamin E acetate dry powder 50 % ................60 g 60 gLudipress [1] ................................................369 g –Sorbitol, crystalline (Merck) ..................................– 233 gKollidon VA64 [1].................................................– 30 gKollidon CL [1] ....................................................– 8 gMagnesium stearate [2] ....................................6 g 4 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press withmedium or high compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................599 mg 502 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................60 N 59 NDisintegration (water) ....................................7 min 7 minFriability .......................................................0.3 % 0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Chemical stability of beta carotene in Formualtion No. 1(40 °C, closed)
0 weeks 15 weeks
Beta carotene/tablet 8.0 mg 7.8 mg
5. Remarks
A colourant pigment should be added to obtain a homogeneous appea-rance of the tablets.
The tablets of Formulation No. 1 could be commercialized in Europe asdietary food because all components are allowed for this application.
BASF Pharma Ingredients Generic Drug Formulations 2005
Beta Carotene + Vitamin C + Vitamin E Tablets (6 mg + 100 mg + 30 mg) page 2
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Beta Carotene + Vitamin C + Vitamin E Tablets(7 mg + 60 mg + 25 mg)
1. Formulation
Betavit® dry powder 10 % (BASF) ..............75 gAscorbic acid, powder (BASF)....................60 gVitamin E acetate dry powder 50 % ...........50 gSorbitol, crystalline [10] ............................240 gKollidon CL [1] ..........................................30 gMagnesium stearate [2] ...............................5 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force.
3. Tablet properties
Weight .................................................497 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................55 NDisintegration ..........................................8 minFriability ................................................< 0.1%
4. Remarks
A colourant pigment should be added to obtain a homogeneous appearance of the tablets.
These tablets could be commercialized in Europe as dietary foodbecause all components are allowed for this application.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene + Vitamin C + Vitamin E Tablets(12 mg + 250 mg + 125 mg)
1. Formulation
Beta Carotene dry powder 10 % ..............125 gAscorbic acid, crystalline (BASF) ..............125 gSodium ascorbate, crystalline (BASF)........141 gVitamin E acetate dry powder SD 50 .......250 g(BASF)Ludipress [1] or Sorbitol, crystalline [10] ....119 gPolyethylene glycol 6000, powder [10] ..........5 gOrange flavour (FDO) .................................15 gSodium cyclamate .....................................10 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with medium compression force.
3. Tablet properties
Weight .................................................790 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................50 NDisintegration ...................................not testedFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene Effervescent Tablets(7 mg)
1. Formulation
Lucarotin® dry powder 10 % CWD (BASF) ..70 gLudipress [1]............................................113 gCitric acid, anhydrous ..............................200 gSodium bicarbonate.................................120 gSodium carbonate .....................................12 gSodium cyclamate .....................................20 gAspartame ................................................15 gOrange flavour ..........................................20 gPolyethylene glycol 6000, powder [6]..........30 g
2. Manufacturing (Direct compression)
Pass all components through o 0.8 mm sieve, mix and press withmedium or high compression force at maximum 30 % of relative atmos-pheric humidity.
3. Tablet properties
Compression force18 kN 26 kN
Weight ......................................................602 mg 605 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarColour.........................................................brown brownHardness ......................................................81 N 108 NDisintegration (water) ..................................45 sec 50 secFriability .......................................................0.4 % 0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Beta Carotene Tablets(15 mg)
1. Formulation
No. 1 No. 2
Beta carotene dry powder 10 %..................160.0 g 150.0 gLudipress [1] .............................................240.0 g –Dicalcium phosphate [9], granulated with .............– 175.0 g5 % Kollidon 30Avicel PH 101 [5] .................................................– 100.0 gKollidon CL [1] ..............................................6.0 g 5.0 gAerosil 200 [4] .....................................................– 2.5 gTalc [10] ..............................................................– 20.0 gCalcium arachinate [2] .........................................– 2.5 gMagnesium stearate [2] .................................2.0 g –
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with amedium compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................400 mg 502 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................59 N 57 NDisintegration .............................................12 min 1 minFriability........................................................0.1% 0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Chemical and physical stability (20–25 °C)
Formulation No. 1: 6 Months 12 Months
Loss of beta carotene 3 % 4 %Hardness 60 N 59 NDisintegration 9 min 7 minFriability 0.15 % 0.16 %
Formulation No. 2: 6 Months 12 Months
Loss of beta carotene < 8 % 9 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Beta Carotene Tablets (15 mg) page 2
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Bran Tablets (250 mg), DC
1. Formulation
Bran wheat (milled <1 mm).......................250 gLudipress [1] ...........................................200 gKollidon 30 [1] .............................................5 gAerosil 200 [4] .............................................4 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with medium compression force.
3. Tablet properties
Weight .................................................477 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................52 NDisintegration ..........................................3 minFriability...................................................0.4 %
4. Remark
If the bran is not milled, the hardness of tablet is higher but the content uniformity is less.
These tablets could be commercialized in Europe as dietary foodbecause all components are allowed for this application.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Bromhexine Tablets(8 mg)
1. FormulationsNo. 1 No. 2
Bromhexine .....................................................8 g 8 gDicalcium phosphate [9]................................179 g –Ludipress [1] .......................................................– 190 gKollidon VA 64 [1].............................................7 g –Kollidon CL [1] .................................................5 g –Magnesium stearate [2] ....................................1 g 1 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low/medium compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................204 mg 202 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................70 N 70 NDisintegration.............................................< 1 min 1 – 2 minFriability .......................................................0.2 % 0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Bromocriptine Tablet Cores(6 mg)
1. Formulation
Bromocriptine mesylate ............................6.1 gLudipress [1] ........................................205.5 gMagnesium stearate [2].............................2.2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high compression force.
3. Tablet properties
Weight .................................................214 mgDiameter .................................................9 mmForm ..................................................biconvexHardness..................................................88 NDisintegration ..........................................4 minFriability...................................................0.7%Dissolution (10 min.) ...............................95.6 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Calcium Chewable Tablets (200 mg Ca)
1. Formulation
Calcium gluconate (Merck) ....................845.0 gCalcium citrate (Merck) .........................500.0 gLudipress LCE [1] .................................297.5 gCitric acid anhydrous, fine granular ........100.0 g(Jungbunzlauer)Polyethylene glycol 6000, powder [6] .......80.0 gOrange flavour (Dragoco) ........................30.0 gAerosil 200 [4]........................................17.0 g.Aspartame, potassium (Searle) ..................5.0 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with highcompression force.
3. Tablet properties
Weight................................................2417 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness................................................201 NFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Calcium Glycerophosphate Tablets(200 mg)
1. Formulation
Calcium glycerophosphate ....................200.0 gLudipress [1].........................................297.5 gMagnesium stearate [2].............................2.5 gAerosil 200 [4] ............................................q.s.
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with high compression force.
3. Tablet properties
Weight .................................................470 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................131 NDisintegration ..........................................7 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Captopril Tablet Cores(25 mg)
1. Formulation
Captopril...................................................25 gLudipress [1] .............................................91 gKollidon CL [1] ............................................2 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.
3. Tablet properties
Weight .................................................122 mgDiameter .................................................8 mmHardness..................................................49 NDisintegration ..........................................1 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Carbamazepine Sustained Release Tablets(200 mg) DC
1. FormulationsA B
Carbamazepine (Fabrica ital. Sintetica) .......200.0 g 200.0 gKollidon SR [1]...........................................100.0 g 100.0 gLudipress LCE [1] ......................................200.0 g 150.0 gKollidon CL-M [1] ................................................– 20.0 gMagnesium stearate [2] .................................2.5 g 2.5 g
2. Manufacturing (Direct compression)
All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and the compressed with high compression force.
3. Tablet properties
A B
Weight ...................................................502.5 mg 472.5 mgDiameter ....................................................12 mm 12 mmHardness.....................................................140 N 164 NFriability ......................................................0.14 % 0.06 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Dissolution of Carbamazepine
BASF Pharma Ingredients Generic Drug Formulations 2005
Carbamazepine Sustained Release Tablets (200 mg) DT page 2
100
80
60
40
00 128 18104 62 16
20
14time [h]
Formulation B
Formulation Arele
ased
dru
g [%
]
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Carbamazepine Tablets(200 mg)
1. Formulation
Carbamazepine .......................................200 gLudipress [1] ...........................................300 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................496 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................128 NDisintegration ..........................................1 minFriability...................................................0.3 %Dissolution 10 min:....................................75 %
30 min: ...................................83 %60 min: ...................................86 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Carbonyl Iron + Copper Sulfate + Manganese Sulfate Tablets (24 mg + 0.16 mg + 3.5 mg)
1. Formulation
Carbonyl iron OF (BASF) .........................24.0 gCopper sulfate........................................0.16 gManganese sulfate ...................................3.5 gLudipress [1] ........................................100.0 gMagnesium stearate [2].............................2.0 g
2. Manufacturing (Direct compression)
Pass all components through a 0.5 mm sieve, mix and press withmedium compression force.
3. Tablet properties
Weight .................................................131 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................95 NDisintegration......................................2 – 3 minFriability...................................................0.3 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Cetylpyridinium Lozenges (2.5 mg)
1. Formulation
Cetylpyridinium chloride (Merck) ................2.5 gLudipress LCE [1] .................................370.0 gPolyethylene glycol 6000, powder [6] .......20.0 gMenthol, crystalline...................................6.0 gAspartame, potassium (Searle) ..................1.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.
3. Tablet properties
Weight .................................................402 mgDiameter ...............................................10 mmForm ...................................................biplanarHardness..................................................80 NDisintegration.......................................>10 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Chlorhexidine Lozenges (5 mg)
1. Formulation
Chlorhexidine (Sigma) ...............................5.0 gSorbitol, crystalline [10] .........................150.0 gKollidon VA64 [1] ......................................5.0 gMenthol, crystalline...................................5.0 gEucalyptol, crystalline ...............................5.0 gAspartame, potassium..............................1.0 gSaccharin, sodium....................................0.1 gAerosil 200 [4] ..........................................2.0 gMagnesium stearate [2].............................1.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.
3. Tablet properties
Weight .................................................175 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................63 NDisintegration.......................................>10 minFriability...................................................0.3 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Choline Theophyllinate Tablets(100 mg)
1. Formulation
Choline theophyllinate ..............................100 gLudipress [1] ...........................................244 gMagnesium stearate [2] ...............................6 g
2. Manufacturing (Direct compression)
Pass all components through a 0.5 mm sieve mix and press with verylow compression force.
3. Tablet properties
Weight .................................................350 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................70 NDisintegration ..........................................4 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Chymotrypsine Tablets(27 mg)
1. Formulation
Chymotrypsine .......................................27.5 gLudipress [1] ..........................................71.5 gMagnesium stearate [2].............................1.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm screen and press with low compression force.
3. Tablet properties
Weight .................................................100 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................67 NDisintegration ..........................................6 minFriability ................................................< 0.1%
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Cimetidine Effervescent Tablets(400 mg)
1. Formulations
No. 1 No. 2
Cimetidine ...................................................400 g 400 gLudipress LCE [1] .........................................680 g 400 gSodium bicarbonate .....................................600 g 500 gTartaric Acid.................................................450 g –Citric Acid...........................................................– 400 gAspartame (Searle) .........................................30 g 27 gPolyethylene glycol 6000, powder [6] ..............90 g 75 gOrange flavour (Dragoco) .................................q.s. q.s.
2. Manufacturing (Direct compression)
Pass the mixture through a 0.8 mm screen and press with medium com-pression force at a maximum of 30 % of relative atmospheric humidity.
3. Tablet properties
No. 1 No. 2
Weight ....................................................2250 mg 1780 mgDiameter ....................................................20 mm 16 mmForm ........................................................biplanar biplanarHardness.....................................................107 N 195 NDisintegration (water) ....................................4 min < 2 minFriability .......................................................1.0 % 1.0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Cimetidine Tablets(200 mg)
1. Formulation
Cimetidine...............................................200 gLudipress [1] ...........................................295 gMagnesium stearate [2] ...............................5 g
2. Manufacturing (Direct compression)
Pass the mixture through a 0.8 mm screen and press with low compres-sion force.
3. Tablet properties
Weight .................................................510 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................92 NDisintegration ..........................................1 minFriability...................................................0.2 %Dissolution (15 min) ...................................88 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Clenbuterol Tablets(20 µg)
1. Formulation
Clenbuterol hydrochloride .......................0.02 gLudipress [1] ........................................99.00 gMagnesium stearate [2]...........................1.00 g
2. Manufacturing (Direct compression)
Mix all components in a turbula mixer and press to tablets with a compression force of 20 kN.
3. Tablet properties
Weight .................................................100 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................75 NDisintegration ..........................................3 min
4. Remark
If the content uniformity does not meet the requirements it would be recommended to prepare a premix of clenbuterol hydrochloride with asmall part of the Ludipress before mixing with the other components ofthe tabletting mixture.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Clobazam Tablets(10 mg)
1. Formulation
Clobazam...............................................10.0 gDicalcium phosphate, DI-TAB [9] ...........135.0 gKollidon VA 64 [1] .....................................7.0 gKollidon CL [1] ..........................................7.0 gMagnesium stearate [2].............................1.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force (15 kN).
3. Tablet properties
Weight .................................................165 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................44 NDisintegration ........................................< 1 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Clomifen Citrate Tablets(50 mg)
1. Formulation
Clomifen citrate ......................................50 mgLudipress [1].........................................100 mgMagnesium stearate [2].............................1 mg
2. Manufacturing (Direct compression)
Mix all components, sieve and press with low compression force.
3. Tablet properties
Weight .................................................154 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................82 NDisintegration ..........................................6 minFriability .................................................0.13 %Dissolution (60 min) .................................100 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Cyproheptadine Tablet(4 mg)
1. Formulation
Cyproheptadine ..........................................4 gLudipress [1] ...........................................194 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Pass all ingredients through a 0.8 mm sieve. Mix and press with very low compression force (4 kN).
3. Tablet properties
Weight .................................................202 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................46 NDisintegration ......................................... 3 minFriability...................................................0.5 %
4. Remark
If the content uniformity does not meet the requirements it would berecommended to prepare a premix of the active ingredient with a smallpart of the Ludipress or with lactose monohydrate before mixing with theother components of the formulation.
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Diazepam Tablet(10 mg)
1. Formulation
Diazepam..................................................10 gLudipress ......................................100 – 480 gMagnesium stearate .........................0.5 – 2.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmediumcompactation force.
3. Tablet properties
Weight .........................................110 – 490 mg.............................according to the formulationForm ...................................................biplanarHardness .............................................> 100 NDisintegration ........................................< 5 minFriability ................................................< 0.1%Dissolution (10 min) .................................100 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Diclofenac Na-dispers-tablet (50 mg)
a) Formulation
Diclofenac Na .......................................50.0mgAvicel® PH 102 .................................143.8mgKollidon® CL........................................50.0mgAerosil® 200 ..........................................5.0mgMagnesium stearate ...............................1.0mg
b) Procedure
Mix the ingredients together, pass through a 0.8mm sieve and compressinto tablets with a force of about 10kN.
Tablet press ...................Korsch PH106, 30 rpmCompression force ................................11.8kN
c) Tablet properties
Weight ...............................................248.0mgS rel ........................................................1.7%Diameter ................................................10mmForm ...................................................biplanarHardness...................................................93NFriability ................................................< 0.1%
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d) Dissolution
e) Content
BASF Pharma Ingredients Generic Drug Formulations 2004
Diclofenac Na-dispers-tablet (50 mg) page 2
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Diclofenac Sustained ReleaseTablets(100 mg)
1. Formulation
Diclofenac sodium (Ivotec).....................100.0 gKollidon SR [1]......................................100.0 gSilicon dioxide, colloidal [4] .......................3.4 gMagnesium stearate [2].............................3.4 g
2. Manufacturing (Direct compression)
All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and then compressed with medium compression force.
3. Tablet properties
Weight ..............................................206.4 mgDiameter .................................................8 mmHardness ................................................195 NFriability.................................................0.09 %
4. Dissolution of Diclofenac-sodium
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Diclofenac Tablets(50 mg)
1. Formulation
Diclofenac sodium ..................................50.0 gLudipress [1] ........................................150.0 gMagnesium stearate [2].............................1.5 gPolyethylene glycol 6000, powder [6] .......15.0 gKollidon CL [1] ........................................10.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................226 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................72 NDisintegration ........................................16 minFriability .................................................<0.1%Dissolution (10 min) ...................................58 %
(15 min) ...................................77%(30 min)...................................99 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Diltiazem Tablets(50 mg)
1. Formulation
Diltiazem...................................................60 gLudipress [1] ...........................................141 gPolyethylene glycol 6000, powder [6]............5 gAerosil 200 [4] .............................................1 gMagnesium stearate [2] ...............................1 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press with low compres-sion force.
3. Tablet properties
Weight .................................................215 mgDiameter .................................................8 mmForm ...................................................biplanarHardness .............................................> 100 NDisintegration .........................................6 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Dimenhydrinate Tablets(50 mg), DC
1. Formulation
Dimenhydrinate .........................................50 gAerosil 200 [4] ..........................................4.0 gLudipress [1] ...........................................140 gKollidon CL [1] .........................................2.0 gMagnesium stearate [2].............................1.5 g
2. Manufacturing (Direct compression)
Mix dimenhydrinate with Aerosil 200, add the other components, sieveand press with low compression force.
3. Tablet properties
Weight .................................................202 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................76 NDisintegration .........................................3 minFriability .................................................<0.1%Dissolution in water (USP, 15 min ...............91%
30 min ...............93 %45 min ...............94 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Doxazosin Mesylate Tablets(1 mg and 4 mg)
1. Formulations
1 mg 4 mg
Doxazosin mesylate .........................................1 g 4 gLudipress [1] ..................................................98 g 95 gMagnesium stearate [2] ....................................1 g 1 g
2. Manufacturing (Direct compression)
Mix all components, sieve and press with low compression force.
3. Tablet properties
1 mg 4 mg
Weight ......................................................100 mg 102 mgDiameter ......................................................6 mm 6 mmForm ........................................................biplanar biplanarHardness ......................................................65 N 66 NDisintegration ...............................................3 min 3 minFriability .....................................................< 0.1% < 0.1%Dissolution in water (USP), 5 min ..................85 % 67%
10 min.................100 % 100 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Enteric Film Coating of Tablets (Organic Solution)
(Acetylsalicylic Acid 100mg)
a) Formulation of the cores
Component Company mg/Tablet
ASA Synopharm 100.0Ludipress BASF 148.5Avicel PH 102 FMC 50.0Magnesium stearate Bärlocher 1.5Total 300.0
b) Manufacture by direct compression:
All the components were mixed for 10 minutes, passed through a sieveof a size of 0.8 mm and compressed into tablets on a rotary press with arate of 40.000 tablets/h at a compression force of 15 kN. Core shapewas convex with a diameter of 9mm and the engraving “BASF”.
Hardness of the tablets was about 60 N.
c) Formulations of the coating suspension:
The formulation is for 5 kg of cores (diameter 9 mm; 300 mg)
Component Parts by weight [g]
No.1 No.2
Kollicoat MAE 100 P 344.52 344.52Triethyl citrate 34.45 34.45Ethanol 4214.60 -Isopropanol/Wasser (70/30) – 4214.60 Total 4593.57 4593.57
Polymer applied: 10.0 mg/cm2
Content of polymer: 7.5 %
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c) Preparation of the spray suspension
Kollicoat MAE 100P and triethyl citrate were stirred into the solvent untilcomplete dissolution.
d) Process Parameters:
Coating pan:............................24” Accela CotaSize of batch: ............................................5 kgInlet air temperature: ...............................50 °COutlet air temperature:........................35-38 °CProduct temperature: .........................30-35 °CInlet air rate: ...........................................70 m_Outlet air rate:.......................................140 m_Spraying pressure: ................................2.0 barNozzle diameter:...................................1.0 mmRate of spraying: ................................30 g/minTime of spraying:......................................2.5 hPre heating ..............................................3 minFinal drying:.............................................5 min
f) Dissolution:
• the drug release is carried out according to USP monograph AspirinDelayed-Release Tablets
BASF Pharma Ingredients Generic Drug Formulations 2005
Enteric Film Coating of Tablets (Organic Solution) (Acetylsalicylic Acid 100 mg) page 2
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method: paddle 100rpm; 37°C0-2h: 0.08 M HCL2 h +: phosphate buffer pH 6.8
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Ethambutol Tablets(400 mg), DC
1. Formulation
Ethambutol .............................................400 gSorbitol, crystalline [10] ............................200 gKollidon VA 64 [1] ......................................20 gKollidon CL [1]...........................................10 gMagnesium stearate [2] ..............................10 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium/high compression force.
3. Tablet properties
Weight .................................................620 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................82 NDisintegration.........................................10 minFriability...................................................0.8 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Etophylline + Theophylline Tablets(100 mg + 22 mg), DC
1. Formulation
Etophylline, powder .................................101 gTheophylline, anhydrous 0,2/0,7 (BASF) .....23 gLudipress [1] .............................................53 gMagnesium stearate [2] ...............................1 gAerosil 200 [4] .............................................2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith low compression force.
3. Tablet properties
Weight .................................................175 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................102 NDisintegration......................................7 – 8 minFriability...................................................0.2 %
4. Remark
To enhance the flowability of the tabletting mixture the amount of Aerosil200 could be increased.
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Famotidine Tablets(40 mg)
1. Formulations
No. 1 No. 2
Famotidine.....................................................40 g 40 gLudipress [1] ................................................105 g 104 gMagnesium stearate [2] ....................................3 g –Stearic acid [7] ....................................................– 2 gAerosil 200 [4]..................................................4 g 4 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................149 mg 148 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................74 N 49 NDisintegration (gastric juice)...........................3 min 1 minFriability......................................................<0.1% 0.3 %Dissolution (10 min)........................................63 % not tested
(30 min) .......................................95 % not tested
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ferrous Fumarate Tablets(200 mg)
1. Formulation
Ferrous fumarate .....................................200 gLudipress [1] ...........................................295 gMagnesium stearate [2] ...............................5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................509 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................92 NDisintegration ..........................................1 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ferrous Sulfate + Manganese Sulfate + Copper Sulfate Tablets(65 mg + 3.5 mg + 0.16 mg)
1. Formulation
Ferrous sulfate, anhydrous ......................65.0 gManganese sulfate ...................................3.5 gCopper sulfate........................................0.16 gLudipress [1] ..........................................70.0 gKollidon 30 [1] ........................................10.0 gMagnesium stearate [2].............................2.0 gAerosil 200 [4] ..........................................3.0 g
2. Manufacturing (Direct compression)
Pass all components through a 0.5 mm sieve, mix and press with high compression force.
3. Tablet properties
Weight .................................................149 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................28 NDisintegration .....................................3 – 4 minFriability...................................................0.4 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ferrous Sulfate Tablets(200 mg)
1. Formulation
Ferrous sulfate, anhydrous .......................203 gLudipress [1] ...........................................185 gKollidon VA 64 [1] ......................................15 gMagnesium stearate [2] ...............................4 gTalc [10] ......................................................4 gAerosil 200 [4] .............................................3 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith medium compression force.
3. Tablet properties
Weight .................................................413 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................110 NDisintegration.........................................13 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Fluoxetine Tablets (20 mg)
1. Formulation
Fluoxetine HCl (BASF).............................22.4 gLudipress [1].........................................176.0 gMagnesium stearate [2].............................1.6 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith low compression force.
3. Tablet properties
Weight .................................................205 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................76 NDisintegration ..........................................5 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Folic Acid Tablets (5 mg)
1. Formulation
Folic acid .................................................5.0 gLudipress [1] ........................................195.0 gMagnesium stearate [2].............................1.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith medium compression force.
3. Tablet properties
Weight .................................................213 mgDiameter .................................................8 mmForm ...................................................biplanarHardness................................................205 NDisintegration ..........................................7 minFriability ................................................< 0.1%
4. Remark
If the content uniformity does not meet the requirements it would berecommended to prepare a premix of the active ingredient with a smallpart of the Ludipress or with lactose monohydrate before mixing with theother components of the formulation.
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Furosemide Tablets(40 mg)
1. Formulation
Furosemide ...............................................40 gLudipress [1] ...........................................158 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................205 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................81 NDisintegration ..........................................2 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Furosemide Tablets(200 mg)
1. Formulation
Furosemide .............................................200 gLudipress [1] ...........................................388 gMagnesium stearate [2] ...............................6 gAerosil 200 [4] .............................................6 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................618 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................159 NDisintegration .....................................3 – 4 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Garlic Extract + Thyme Extract TabletsCores with Vitamin C(300 mg + 25 mg + 100 mg)
1. Formulation
Garlic extract, granulated (Aflopa).............300 gThyme extract, powder (Aflopa) ..................25 gAscorbic acid, crystalline (BASF)...............100 gKollidon CL [1]...........................................14 gLudipress [1] ...........................................268 gMagnesium stearate [2] ...............................7 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tabletswith medium compression force.
3. Tablet properties
Weight..................................................714 mgDiameter ...............................................12 mmForm ..................................................biconvexHardness..................................................50 NDisintegration ..........................................9 minFriability .....................................................0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ginkgo Extract Tablets(40 mg)
1. Formulation
Ginkgo biloba extract, dry powder ............240 g(Biogen)Aerosil 200 [4] .............................................1 gKollidon CL [1] ............................................4 gLudipress [1] ...........................................203 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Mix the Ginkgo extract with Aerosil 200, add the other components,pass through a 0.8 mm sieve and press to tablets with low compressionforce.
3. Tablet properties
Weight ......................................................254 mgDiameter ......................................................8 mmForm ........................................................biplanarHardness ......................................................81 NDisintegration ...............................................8 minFriability .....................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Glibenclamide (Glyburide) Tablets(5 mg)
1. Formulation
No. 1 No. 2
Glibenclamide micronized (Guidotti)................5.0 g –Glibenclamide .....................................................– 5.0 gLudipress [1] .............................................120.0 g 194.0 gMagnesium stearate [2] .................................0.5 g 1.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force (about 10 kN).
3. Tablet properties
No. 1 No. 2
Weight ......................................................125 mg 201 mgDiameter ......................................................7 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................80 N 107 NDisintegration ............................................2-3 min 3 – 4 minFriability .....................................................< 0.2 % < 0.1%Dissolution (pH 7.4) (10 min) ...........................50 % –
(30 min) ...........................69 % –(60 min) ...........................75 % –
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4. Influence of the compression force on the physical tablet properties(Formulation No. 2)
Compression forceProperty 5 kN 10 kN 20 kN 25 kN
Hardness 47 N 107 N 158 N 191 NDisintegration 2 – 3 min 3 – 4 min 3 – 4 min 5 minFriability < 0.1% < 0.1% < 0.1% < 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
Glibenclamide (Glyburide) Tablets (5 mg) page 2
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Griseofulvin Tablets(125 mg)
1. Formulation
Griseofulvin, micronized (Aldrich) ..............125 gLudipress [1] ...........................................250 gPolyethylene glycol 6000, powder [6] ..........10 gAerosil 200 [4] ...........................................19 g
2. Manufacturing (Direct compression)
Pass all components through a 0.5 mm sieve, mix and press with low compression force applying a vibrating hopper.
3. Tablet properties
Weight .................................................367 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................79 NDisintegration ..........................................1 minFriability...................................................0.3 %Dissolution, 20 min ...................................78 %
40 min ...................................88 %60 min ...................................92 %
4. Remark
The flowability of the tabletting mixture should be increased by higheramounts of Ludipress or/and Aerosil 200.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Hydrochlorothiazide + Potassium ChlorideTablet Cores (50 mg + 300 mg)
1. Formulation
Hydrochlorothiazide...................................50 gPotassium chloride ..................................300 gKollidon CL [1]...........................................15 gAerosil 200 [4] .............................................2 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press.
3. Tablet properties
Weight .................................................369 mgDiameter .................................................9 mmForm ..................................................biconvexHardness..................................................88 NDisintegration ........................................< 1 minDissolution of hydrochlorothiazide, .............89 %10 min
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Hydrochlorothiazide Tablets(50 mg), DC
1. Formulation
Hydrochlorothiazide...................................50 gLudipress [1] ...........................................280 gMagnesium stearate [2] ...............................2 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................328 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................70 NDisintegration ..........................................3 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ibuprofen Tablets(400 mg), DC
1. Formulations
Ibuprofen (Francis) ...................................400 gAerosil 200 [4] ............................................ 4 gLudipress [1] ...........................................342 gKollidon CL [1] ............................................8 gMagnesium stearate [2] ...............................8 g
2. Manufacturing (Direct compression)
Pass ibuprofen and magnesium stearate through a 200 µm sieve, mixwith the other components and press with medium compression force.
3. Tablet properties
Weight ......................................................752 mgDiameter ....................................................16 mmHardness .....................................................112 NDisintegration ..........................................2 – 3 minFriability .......................................................0.4 %Dissolution, 10 min ........................................82 %
15 min.........................................91%
4. Physical stability (20–25ºC)
6 Months 8 Months 12 Months
Hardness – 121 N 120 NDisintegration – 2 – 3 min –Friability – 0.4 % 0.2 %Dissolution, 10 min 85 % – 89 %
20 min 87% 91% 88 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Ibuprofen Tablets (600 mg), DC
1. Formulations
Ibuprofen 50 (BASF) ................................600 gAerosil 200 [4] .............................................9 gAvicel PH 200 [5] .....................................108 gKollidon VA 64 [1] ......................................50 gKollidon CL [1] ..........................................27 gMacrogol 6000 powder [6] ...........................6 g
2. Manufacturing (Direct compression)
Mix ibuprofen with Aerosil 200, add the other components and presswith low compression force.
3. Tablet properties
Weight .................................................793 mgDiameter ...............................................16 mmHardness..................................................80 NDisintegration ........................................<1 minFriability...................................................0.8 %
BASF Pharma Ingredients Generic Drug Formulations 2004
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4. Dissolution (Storage 20-25°C)
BASF Pharma Ingredients Generic Drug Formulations 2005
Ibuprofen Tablets (600 mg), DC page 2
100
80
60
40
20
00 3
Months
6 9
10 min
15 min
30 min
drug
rele
ased
[%]
12
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Indomethacin Sustained Release Tablets(75 mg)
1. Formulation
Indomethacin (Synopharm) ........................75 gKollidon SR [1].........................................125 gLudipress LCE [1] ....................................100 gSilicon dioxide, colloidal [4] .......................1.5 gMagnesium stearate [2].............................1.5 g
2. Manufacturing (Direct compression)
All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and then compressed with medium compression force.
3. Tablet properties
Diameter ...............................................10 mmWeight .................................................303 mgHardness ................................................163 NFriability .................................................0.01%
4. Dissolution of Indomethacin
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
100
80
60
40
0
20
0 128 18104 62 1614time [h]
75 rpm medium:phosphate buffer pH 6.2
rele
ased
dru
g [%
]
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Indomethacin Tablets(50 mg), DC
1. Formulation
Indomethacin ............................................50 gLudipress [1] ...........................................227 gKollidon CL [1] ..........................................20 gMagnesium stearate [2] ...............................3 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.
3. Tablet properties
Weight .................................................303 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................176 NDisintegration ..........................................3 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Indomethacin Tablets(100 mg)
1. Formulation
Indomethacin ..........................................100 gLudipress [1] ...........................................397 gMagnesium stearate [2] ...............................3 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................500 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................61 NDisintegration ..........................................5 minFriability...................................................0.4 %
4. Remark
If the flowability of indomethacin is not good it should be mixed with alow percentage of Aerosil 200.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Isosorbide Dinitrate Tablets(5 mg)
1. Formulation
Isosorbide dinitrate + Lactose (4+6) .........12.5 gLactose monohydrate [8] .......................152.1 gKollidon 30 [1] ..........................................5.4 gKollidon CL [1] .........................................9.0 gMagnesium stearate [2].............................1.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................184 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................45 NDisintegration .......................................< 1 minFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Khellin Tablets(25 mg)
1. Formulation
Khellin ......................................................25 gLudipress [1] ...........................................124 gMagnesium stearate [2] ...............................1 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix intensively and presswith low compression force (10 kN).
3. Tablet properties
Weight .................................................150 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................65 NDisintegration .................................about 1 minFriability.................................................0.25 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Labetalol Tablets(50 mg)
1. Formulation
Labetalol, fine powder (Joy Sun)..............50.0 gLudipress [1] ..........................................98.4 gAerosil 200 [4] ..........................................0.8 gMagnesium stearate [2].............................0.8 g
2. Manufacturing (Direct compression)
Mix all components, sieve through a 0.8 mm screen and press with low compression force.
3. Tablet properties
Weight .................................................150 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................71 NDisintegration ..........................................1 minFriability...................................................0.2 %Dissolution (gastric juice,paddle, 50 rpm) 10 min............96.6 %
15 min .............100 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Levamisole Tablets(150 mg)
1. Formulation
Levamisole hydrochloride .........................150 gLudipress [1] ...........................................300 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................458 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................80 NDisintegration .....................................3 – 4 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Levothyroxine Tablets (0.05 mg)
1. Formulations
No. 1 No. 2
I. Levothyroxine sodium..................................0.05 g 0.05 gCitric acid, anhydrous..........................................– 10.00 gMagnesium stearate ....................................1.00 g 1.00 g
II. Ludipress [1] .............................................99.00 g 89.00 g
2. Manufacturing (Direct compression)
Prepare premix I, add II and pass the mixture thorugh a 0.8 mm sieve.Mix and press with low compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................103 mg 101 mgDiameter ......................................................6 mm 6 mmForm ........................................................biplanar biplanarHardness ......................................................52 N 45 NDisintegration...........................................1 – 2 min 4 minFriability........................................................0.1% <0.1%Content uniformity not controlled
4. Remarks
If the content uniformity of formulation No. 1 does not meet the require-ments it would be recommended to add a small part of Ludipress (= part II) to the premix I.
The function of citric acid in formulation No. 2 is the stabilization of the active ingredient. The effectiveness was not controlled in this formulation.
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Lisinopril Tablets(10 mg)
1. Formulation
Lisinopril ...................................................10 gLudipress [1] ...........................................139 gMagnesium stearate [2] ...............................1 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix intensively and presswith low compactation force (10 kN).
3. Tablet properties
Weight .................................................152 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................94 NDisintegration......................................2 – 3 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Lycopene Tablet Cores(6 mg)
1. Formulation
LycoVit 10 % dry powder............................60 gLudipress [1] ...........................................330 gKollidon CL [1] ............................................6 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Mix the LycoVit dry powder with the other components, sieve through a0.8 mm screen and press with medium to high compression force.
3. Tablet properties
Weight .................................................400 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness..................................................80 NDisintegration ..........................................4 minFriability .................................................<0.1%
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BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
Magaldrate Chewable Tablets(500 mg)
1. Formulation
I. Magaldrate USP ......................................500 gLactose monohydrate [8] .........................400 gOrange flavour (FDO) .................................50 g
II. Kollidon 90 F [1] ........................................20 gBanana flavour (FDO)...................................6 gCocos flavour (FDO) ....................................6 gSaccharin sodium........................................1 gWater ......................................................180 g
III. Aerosil 200 [4] .............................................5 gMagnesium stearate [2] ...............................3 g
2. Manufacturing (Wet granulation)
Granulate mixture I with solution II, pass through a 0.8 mm sieve, dry,mix with III and press with low compression force.
3. Tablet properties
Weight................................................1000 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................72 NDisintegration (water) .............................60 minFriability ................................................< 0.1%Taste .......................................................good
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Magaldrate Chewable Tablets (1000 mg)
1. Formulation
Magaldrate (Reheis) ...............................1000 gLudipress LCE [1] ....................................930 gLutrol E4000F [1] .......................................60 gAspartame, potassium (Searle) ...................10 gPeppermint flavour .....................................q.s.
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press withmedium compression force.
3. Tablet properties
Weight ..............................................2,000 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..............................................>250 NFriability .................................................<0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Magaldrate Dispersible Tablets(700 mg)
1. Formulation
Magaldrate..............................................700 gLactose monohydrate [8] .........................435 gKollidon 90 F [1] ........................................10 gKollidon CL [1] ..........................................50 gMagnesium stearate [2] ...............................5 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force (4 – 6 kN).
3. Tablet properties
Weight ..............................................1,200 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness ................................................125 NDisintegration (water)..............................25 secFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Magnesium Carbonate Tablets(260 mg)
1. Formulation
Magnesium carbonate USP......................262 gLudipress [1] ...........................................238 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.
3. Tablet properties
Weight .................................................499 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................168 NDisintegration ..........................................1 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Mebendazole Tablets (100 mg)
1. Formulation
Mebendazole...........................................100 gLudipress [1] ...........................................196 gMagnesium stearate [2] ...............................4 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................294 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................73 NDisintegration ..........................................2 minFriability...................................................0.5 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Meprobamate + Phenobarbital Tablets(400 mg + 30 mg), DC
1. Formulation
Meprobamate..........................................400 gPhenobarbital............................................30 gAvicel PH 101 [5] .......................................76 gKollidon VA 64 [1] ......................................13 gKollidon CL [1] ..........................................21 gTalc [10] ......................................................8 gAerosil 200 [4] .............................................1 gCalcium arachinate [2] .................................1 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force.
3. Tablet properties
Weight .................................................551 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................87 NDisintegration ........................................< 1 minFriability...................................................0.9 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Meprobamate Tablets(400 mg), DC
1. Formulation
Meprobamate..........................................400 gAvicel PH 101 [5] .......................................80 gCorn starch [3] ..........................................30 gKollidon VA 64 [1] ......................................20 gKollidon CL [1] ..........................................20 gTalc [10] ......................................................7 gMagnesium stearate [2] ...............................3 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high compression force (20 KN).
3. Tablet properties
Weight .................................................560 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration ......................................< 10 minFriability ..................................................0.6 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Metamizol Tablets(500 mg)
1. Formulations
No. 1 No. 2
Metamizol sodium ........................................500 g 500 g(= Dipyrone)Ludipress [1] ................................................100 g –Avicel PH 101 [5] .................................................– 100 gKollidon 30 [1].....................................................– 15 gKollidon CL [1] ...............................................10 g 25 gMagnesium stearate [2]...................................10 g –Aerosil 200 [4]..................................................5 g 1 gTalc [10] ..............................................................– 8 gCalcium arachinate [2] .........................................– 1 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.5 mm sieve and press with low compression force.
3. Tablet properties
No. 1 No. 2
Weight ......................................................625 mg 654 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness.....................................................120 N 62 NDisintegration ...............................................5 min 2 minFriability .......................................................0.3 % 1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Methyl Cysteine Tablets(100 mg)
1. Formulation
Methyl cysteine hydrochloride ..................100 gLudipress [1] ...........................................200 gMagnesium stearate [2].............................3 mgMenthol ...................................................4 mg
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low compression force.
3. Tablet properties
Weight .................................................307 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................55 NDisintegration......................................2 – 3 minFriability...................................................0.3 %
4. Physical stability (12 months, 20–25 ºC)
Weight .................................................307 mgHardness..................................................85 NDisintegration......................................2 – 3 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Metoclopramide Tablets(10 mg)
1. Formulation
Metoclopramide hydrochloride ................10.0 gLudipress [1] ..........................................89.5 gMagnesium stearate [2].............................0.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.
3. Tablet properties
Weight .................................................100 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................35 NDisintegration (gastric juice) ......................3 minFriability ...................................................0.1%Dissolution (15 min) .................................100 %
4. Physical stability (18 months, 20–25 ºC)
Weight .................................................100 mgHardness..................................................35 NDisintegration (gastric juice) ......................3 minFriability ...................................................0.1%Dissolution (15 min) .................................100 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Metronidazole Tablet Cores(400 mg)
1. Formulation
Metronidazole .........................................400 gAvicel PH 102 [5] .....................................150 gKollidon VA 64 [1] ......................................25 gKollidon CL [1]...........................................15 gAerosil 200 [4] .............................................5 gPolyethylene glycol 6000, powder [6]..........50 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high compression force (25 – 30 kN).
3. Tablet properties
Weight .................................................645 mgDiameter ...............................................12 mmForm ..................................................biconvexHardness..................................................87 NDisintegration......................................1 – 2 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
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Metronidazole Tablets(200 mg)
1. Formulation
Metronidazole .........................................200 gAvicel PH 101 [5] .....................................200 gKollidon 30 [1] .............................................6 gKollidon CL [1]...........................................10 gAerosil 200 [4] .............................................5 gMagnesium stearate [2] ...............................5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high compression force (25 – 30 kN).
3. Tablet properties
Weight .................................................426 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................133 NDisintegration......................................1 – 2 minFriability ................................................< 0.1%
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Multivitamin + Calcium + Iron Tablets(1 RDA of Vitamins)
1. Formulation
Vitamin A acetate dry powder ...................5.0 g500,000 i. u./g (BASF)Vitamin D dry powder ..............................2.0 g100,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................1.2 gRiboflavin (BASF)......................................1.8 gNicotinamide ..........................................12.0 gVitamin E acetate dry powder SD 50 ........4.0 g(BASF)Ascorbic acid, powder (BASF) .................50.0 gFerrous fumarate ....................................60.0 gDibasic calcium phosphate [9], .............200.0 ggranulated with 5 % Kollidon 30 [1]Calcium carbonate................................125.0 gAvicel PH 101 [5] ....................................45.0 gAerosil 200 [4] ..........................................1.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press to tablets.
3. Tablet properties
Weight .................................................500 mgDiameter ...............................................11 mmForm ...................................................biplanarHardness..................................................75 NDisintegration (water)...........................2 – 3 minFriability...................................................0.3 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Multivitamin + Carbonyl Iron Tablets(1–2 RDA of Vitamins)
1. Formulation
Vitamin A acetate dry powder500,000 i. u./g (BASF) .............................10.0 gThiamine mononitrate (BASF) ....................2.2 gRiboflavin (BASF)......................................2.2 gNicotinamide ..........................................16.5 gCalcium D-pantothenate (BASF) ..............11.5 gPyridoxine hydrochloride (BASF)................2.2 gCyanocobalamin, dry powder 0.1% ..........6.0 gAscorbic acid, powder (BASF) .................85.0 gVitamin E acetate dry powder SD 50 .......31.0 g(BASF).............................................................Ludipress [1].........................................311.0 gCarbonyl iron powder OF (BASF) .............10.0 gMagnesium stearate [2].............................3.0 gOrange flavour..........................................7.2 gSaccharin sodium.....................................2.5 g
2. Manufacturing (Direct compression)
Mix all ingredients, pass through a 0.8 mm sieve, mix and press withhigh compression force (20 kN).
3. Tablet properties
Weight .................................................500 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................69 NDisintegration.........................................12 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Multivitamin + Minerals Tablets with BetaCarotene(1 RDA of Vitamins)
1. Formulation
Beta carotene dry powder, Betavit 20% ........16.5 g(BASF)Thiamine mononitrate (BASF) .........................1.7 gRiboflavin (BASF)...........................................1.9 gNicotinamide (Degussa) ...............................22.0 gCalcium D-pantothenate (BASF) ...................12.0 gPyridoxine hydrochloride (BASF) ....................2.2 gAscorbic acid, cryst. (BASF).........................72.0 gVitamin E acetate dry powder 50 % (BASF) ...66.0 gFerrous fumarate .........................................54.7 gMagnesium oxide, high density type ..........165.8 g(Merck)Copper II oxide, powder (Merck) ....................2.5 gManganese sulfate (Merck) ............................6.9 gZink oxide (Merck) .......................................18.7 gPotassium chloride (Baker) ..........................76.3 gDicalium phosphate, DI-TAB [9] ..................550.0 gAvicel PH 102 [5] .........................................60.0 gCroscarmellose [5] ......................................32.0 gSyloid® 244 FP (Grace) ..................................6.0 gStearic acid [7] ..............................................6.0 gMagnesium stearate [2] .................................6.0 g
2. Manufacturing (Direct compression)
All ingredients were passed through a 0.8 mm sieve, blended in a Tur-bula mixer and then compressed with medium to high compressionforce.
3. Tablet properties
Weight ................................................1193 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................112 NFriability ...................................................0.1%
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Stability of beta carotene
Because beta carotene may be the most sensitive vitamin in this formu-lation it’s stability at room temperature and at 40°C/75 % relative humi-dity was determined
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin + Minerals Tablets with Beta Carotene (2 RDA of Vitamins) page 2
50
60
70
80
90
100
20-25°C40°C/75% r.h.
20 40 600Weeks
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Multivitamin + Minerals Tablets with BetaCarotene(2 RDA of Vitamins)
1. Formulation
No. 1 No. 2
Beta carotene dry powder 10 %..................150.0 g 50.0 gThiamine mononitrate (BASF) .........................2.5 g 3.0 gRiboflavin (BASF)...........................................2.9 g 3.0 gPyridoxine hydrochloride (BASF) ....................2.0 g 3.0 gNicotinamide...............................................22.0 g 22.0 gCalcium D-pantothenate (BASF) ...................12.0 g 12.0 gAscorbic acid for direct compression ..........110.0 g 100.0 g(Roche)Calcium phosphate, dibasic [9] ..................550.0 g 550.0 gFerrous fumarate .........................................82.0 g 80.0 gMagnesium oxide ......................................166.0 g 160.0 gCupric sulfate................................................2.5 g 2.0 gManganese sulfate ......................................13.8 g 14.0 gPotassium chloride ......................................57.2 g 50.0 gZinc sulfate .................................................37.0 g 37.0 gAvicel PH 102 [5] .........................................57.0 g 60.0 gKollidon CL [1] ............................................50.0 g 50.0 gStearic acid [7] ..............................................5.7 g 6.0 gMagnesium stearate [2] .................................5.0 g 5.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high compression force.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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3. Tablet properties
No. 1 No. 2
Weight ....................................................1300 mg 1205 mgDiameter ....................................................16 mm 16 mmForm ........................................................biplanar biplanarHardness ......................................................94 N 88 NDisintegration (water) ..................................< 1 min < 1 minFriability ..........................................................1% < 0.1%
4. Chemical stability of formulation No. 2 (20–25°C)
Storage time Beta Carotene B1 B2 B5 B6 C
6 Months 100 % 98 % 98 % 100 % 97% 95 %12 Months 92 % 96 % 92 % 99 % 96 % 94 %
5. Remark
These tablets could be commercialized in Europe as dietary foodbecause all components are allowed for this application.
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin + Minerals Tablets with Beta Carotene (2 RDA of Vitamins) page 2
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Multivitamin Chewable Tablets for Children
1. Formulation
Vitamin A acetate dry powder....................7.0 g500,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................1.2 gRiboflavin (BASF)......................................1.2 gNicotinamide ..........................................20.0 gPyridoxine hydrochloride (BASF)................1.8 gCyanocobalamin 0.1% dry powder ............6.5 g(BASF)Ascorbic acid, powder (BASF) .................60.0 gVitamin D3 acetate dry powder100,000 i. u./g (BASF) ...............................5.0 gVitamin E acetate ..................................31.0 gdry powder SD 50 (BASF)Sorbitol, crystalline [10] .........................200.0 gSucrose, crystalline...............................200.0 gKollidon VA 64 [1] ...................................20.0 gAerosil 200 [4] ..........................................1.0 gOrange flavour, dry powder .....................30.0 gRaspberry flavour, dry powder...................6.0 gPassion fruit flavour, dry powder................3.0 gCyclamate sodium....................................2.0 g
2. Manufacturing (Direct compression)
Mix all ingredients, pass through a 0.8 mm sieve and press with mediumto high compression force (20 kN).
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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3. Tablet properties
Weight .................................................575 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................100 NDisintegration ..........................................7 minFriability...................................................0.2 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Chewable Tablets for Children page 2
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Multivitamin Effervescent Tablets I, DC(1 – 2 RDA of Vitamins)
1. Formulation
Lucarotene Dry Powder 10 % .................23.0 gCWD G/Y (BASF)Dry Vitamin E acetate 50 % DC (BASF).....40.0 gThiamine mononitrate (BASF) ....................2.0 gRiboflavin C (BASF) ..................................2.0 gNicotinamide ..........................................22.0 gCalcium D-pantothenate (BASF) ..............11.0 gPyridoxine hydrochloride (BASF)................2.0 gCyanocobalamin 0.1% dry powder ............6.0 gAscorbic acid, powder (BASF) .................85.0 gLudipress LCE [1] .................................477.0 gSodium bicarbonate .............................600.0 gTartaric acid .........................................400.0 gPolyethylene glycol 6000, powder [6] ......90.0 gOrange flavour (Dragoco) ........................60.0 gApartame (Searle) ...................................30.0 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve, mix and press withhigh compression force at a maximum of 30 % of relative atmospherichumidity.
3. Tablet properties
Weight................................................1850 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................91 NDisintegration (water) ...............................1 minFriability ..................................................0.6 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Multivitamin Effervescent Tablets II, DC(3–4 RDA of Vitamins)
1. Formulations
No. 1 No. 2
Thiamine mononitrate (BASF) .........................5.5 g 5.5 gRiboflavin (BASF)...........................................5.5 g 5.5 gPyridoxine hydrochloride (BASF) ...................6.5 g 6.5 gNicotinamide ............................................60.0 g 60.0 gCalcium D-pantothenate (BASF)...................30.0 g 30.0 gAscorbic acid, powder (BASF) ....................200.0 g 200.0 gCyanocobalamin 0.1% dry powder ...............20.0 g 20.0 gVitamin A palmitatedry powder 325000 i. u./g CWD (BASF) ........30.0 g 30.0 gVitamin E acetate dry powder 50 % .............110.0 g 50.0 gCitric acid, powder ..............................................– 500.0 gTartaric acid, powder .................................400.0 g –Sodium bicarbonate ..................................500.0 g 500.0 gLudipress [1] ..........................................600.0 g 500.0 gPolyethylene glycol 6000, powder [6]............70.0 g 70.0 gSaccharin sodium .........................................0.5 g 0.5 gCyclamate sodium.......................................40.0 g 40.0 gSucrose, crystalline ...................................200.0 g 200.0 gFructose ..........................................200.0 g 200.0 gFlavours (Firmenich) ...................................100.0 g 100.0 g
2. Manufacturing (Direct compression)
Mix all components, sieve through a 0.8 mm screen and press with high compression force at maximum 30 % relative atmospheric humidity.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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3. Tablet properties
No. 1 No. 2
Weight ....................................................2200 mg 2495mgDiameter ....................................................20 mm 20 mmForm ........................................................biplanar biplanarHardness ......................................................98 N 197 NDisintegration (water)................................1 – 2 min 2 minFriability .......................................................1.0 % 0.4 %
4. Chemical stability of formulation No. 1 (after 12 months at 20–25 ºC;HPLC)
Vitamin B1 ...................................................93 %Vitamin B6 ...................................................89 %Vitamin B12...................................................88 %Vitamin A ......................................................79 %All other vitamins .........................................> 95 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Effervescent Tablets II, DC (3–4 RDA of Vitamins) page 2
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Multivitamin Tablet Cores with Beta-Carotene(1–2 RDA of Vitamins)
1. Formulation
Vitamin mixture (BASF, see “Remark”)....270.2 gLudipress [1] ..........................................69.1 gMagnesium stearate [2].............................3.3 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with high compression force.
3. Tablet properties
Weight .................................................459 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness..................................................97 NDisintegration (water)..............................13 minFriability .....................................................0 %Content uniformity of Vitamin B1,B2, B6 and folic acid ................conform to DAB
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Remark
The used vitamin mixture had the following composition:
Vitamin A acetate dry powder .....................1.27%500,000 i. u./gBeta carotene dry powder BetaVit 10 %......11.50 %Thiamine mononitrate..................................1.24 %Riboflavin ..................................................0.96 %Nicotinamide.............................................11.50 %Calcium D-pantothenate .............................1.91%Pyridoxine hydrochloride .............................1.15 %Cyanocobalamin gelatin coated 1% .............2.86 %D-Biotin, 1% trituration ...............................1.91%Folic acid ...................................................0.09 %Ascorbic acid............................................38.20 %Vitamin D3 dry powder 100,000 i. u./g..........0.76 %Vitamin E acetate dry powder 50 DC..........28.40 %Phytomenadione dry powder 5 % GFP..........0.19 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Tablet Cores with Beta-Carotene (1–2 RDA of Vitamins) page 2
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Multivitamin Tablets, DC(1–2 RDA of Vitamins)
1. Formulation
No. 1 No. 2
Vitamin A acetate dry powder ......................10.0 g 10.0 g500,000 i. u./g (BASF) ...........................................Thiamine mononitrate (BASF) .........................2.2 g 2.2 gRibolfavin (BASF)...........................................2.2 g 2.2 gNicotinamide ...............................................16.5 g 16.5 gCalcium D-pantothenate (BASF) ...................11.5 g 11.5 gPyridoxine hydrochloride (BASF) ....................2.2 g 2.2 gCyanocobalamin 0.1% dry powder.................6.0 g 6.0 gAscorbic acid, powder (BASF)......................85.0 g 85.0 gVitamin E acetate dry powder SD 50 ...........31.0 g 31.0 g(BASF)Ludipress [1] .............................................321.0 g –Microcrystalline cellulose, Vitacel®.......................– 300.0 g(Rettenmaier)Kollidon VA 64 [1] ................................................– 21.0 gMagnesium stearate [2] .................................3.0 g 3.0 gOrange flavour ..............................................7.2 g 7.2 gSaccharin sodium .........................................2.5 g 2.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve, mix and press withmedium compression force (15 kN).
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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3. Tablet properties
No. 1 No. 2
Weight ......................................................500 mg 501 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................68 N 195 NDisintegration (water) ....................................5 min 6 minFriability .......................................................0.2 % < 0.1%
4. Chemical stability of formulation No. 1 (after 12 months at 20–25 ºC)
Vitamin A ..............................................88 %Vitamin B6 ..............................................94 %Calcium D-pantothenate ................................92 %Vitamin B12 ..................................................... 90 %All other vitamins .........................................> 95 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Tablets, DC (1–2 RDA of Vitamins) page 2
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Multivitamin Tablets for Dogs
1. Formulation
Vitamin A + D3 dry powder ......................4.0 g500,000 + 50,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................0.5 gRiboflavin (BASF)......................................0.7 gNicotinamide ............................................5.0 gCalcium D-pantothenate (BASF)................1.0 gPyridoxine hydrochloride (BASF)................0.5 gCyanocobalamin gelatin coated 1% ..........0.5 g(BASF)Folic acid ...............................................0.05 gCholine bitartrate ....................................20.0 gVitamin E acetate dry powder SD 50 ......20.0 g(BASF)Ludipress [1] ........................................196.0 gMagnesium stearate [2].............................2.0 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with low compression force.
3. Tablet properties
Weight .................................................250 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................77 NDisintegration (water) ...............................7 minFriability .....................................................0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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Multivitamin Tablets with Beta Carotene(1–2 RDA of Vitamins)
1. Formulations
No. 1 No. 2
Beta Carotene dry powder 10 % Betavit® .....10.0 g –(BASF) .................................................................Beta Carotene dry powder 10 % ..........................– 70.0 gPharma (BASF)Thiamine mononitrate (BASF) .........................2.0 g 2.2 gRiboflavin (BASF)...........................................2.0 g 2.2 gNicotinamide ...............................................16.0 g 6.5 gCalcium D-pantothenate (BASF) ...................11.0 g 11.5 gPyridoxine hydrochloride (BASF) ....................2.0 g 2.2 gCyanocobalamin 0.1% dry powder.................6.0 g 6.0 gAscorbic acid, powder (BASF)......................85.0 g 85.0 gVitamin E acetate dry powder SD 50 ............31.0 g 32.0 g(BASF)Ludipress [1] .............................................321.0 g 210.0 gKollidon VA 64 [1] ................................................– 7.0 gMagnesium stearate [2] .................................3.0 g 3.0 gOrange flavour ..............................................7.0 g 7.0 gSaccharin sodium .........................................2.0 g 2.5 g
2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve, mix and press withmedium compression force.
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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3. Tablet properties
No. 1 No. 2
Weight ..........................................508 mg 449 mgDiameter ...........................................12 mm 12 mmForm ..........................................biplanar biplanarHardness ..............................................72 N 47 NDisintegration (water) ....................................5 min 10 minFriability ...........................................< 0.1% 0.15 %
4. Chemical stability of vitamins in formulation No. 1 (20–25 °C, HPLC)
Storage time Beta Carotene B1 B2 B5 B6 C
6 Months 100 % 100 % 90 % 100 % 98 % 96 %12 Months 100 % 98 % 87% 100 % 97% 94 %
5. Remark
Formulation No. 1 could be commercialized in Europe as dietary foodbecause all components are allowed for this application.
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Tablets with Beta Carotene (1–2 RDA of Vitamins) page 2
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Multivitamin Tablets with Copper and Zinc
1. Formulation
Vitamin mixture (BASF, see “Remark”) .....1000 gAerosil 200 [4] .............................................5 gLudipress [1] ...........................................150 gAvicel PH102 [5] ......................................120 gKollidon VA64 [1] .......................................25 gMagnesium stearate [2] ..............................10 gTalc [10] ....................................................10 g
2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with highcompression force.
3. Tablet properties
Weight ...............................................1350 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................62 NDisintegration (water) ...............................3 minFriability...................................................1.0 %
BASF Pharma Ingredients Generic Drug Formulations 2004
2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)
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4. Remark
The used vitamin mixture had the following composition:Thiamine mononitrate...............................3.9 %Riboflavin 100 ..........................................0.4 %Nicotinamide ..........................................10.1%Calcium D-pantothenate ..........................2.9 %Pyridoxine hydrochloride ..........................1.2 %Cyanocobalamin gelatin coated 0.1% .......2.6 %Folic acid .................................................0.1%Ascorbic acid fine powder ......................63.4 %Vitamin E acetate dry powder 500 SD .......9.1%Cupper oxide...........................................0.3 %Zinc sulphate ...........................................6.0 %
BASF Pharma Ingredients Generic Drug Formulations 2005
Multivitamin Tablets with Copper and Zinc page 2
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