4 drug profile.pdf

Chapter 4 Drug and Excipient Profile

School of Pharmaceutical Sciences Shobhit University, Meerut 48

4.0 DRUG AND EXCIPlENT PROFILE

4.1 DOMPERIDONE1-16

Category Peripheral dopamine receptor antagonist; antiemetic.

Molecular Weight 425.911 g/mol

Molecular Formula C22H24 ClN5O2

Melting Point 242.5 0C

pKa 7.9

IUPAC Name 5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-

yl)propyl] piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

Structure

N

HNO

N

N

NHO

Cl

Description Domperidone is a benzimidazole derivatives and a member of

dopamine receptor antagonist.

Dose Adult - 20 – 40 mg t.d.s ; Children - 0.3 mg / kg t.d.s.

Solubility Very slightly soluble in water and alcohol, slightly soluble in

methanol.

Pharmacology Domperidone acts as a gastrointestinal emptying adjunct and

peristaltic stimulant. The antiemetic properties are related to

dopamine receptor blocking activity at both chemoreceptor trigger

zone and gastric level. It shows affinity for the D2 and D3 dopamine

receptors.

Pharmacokinetics

Absorbed from the GIT, undergoes first pass metabolism in liver.

Bioavailability is 5% following oral administration. Metabolites are

excreted in faeces and in the urine. Plasma half-life is 7 - 8 hours.

Onset of action is within 1 hour of administration.

Routes of Administration Oral, intravenous, rectal

Indications As an anti-emetic for relief on nausea and vomiting of any cause.

Radiation, uremia. Reflux oesophagitis.

http://en.wikipedia.org/wiki/Gram

http://en.wikipedia.org/wiki/Mole_(unit)

http://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclature



4.2 GLICLAZIDE1,2,17-23

Drug Interactions

This medication enhances movement in the digestive tract, it may

affect the absorption and action of other medications. Opioid

analgesics and antimuscarinics antagonize its effects.

Category Hypoglycemic Agents, Sulfonylureas, Antidiabetic

Molecular Weight 323.412 g/mol

Molecular Formula C15H21N3O3S

Melting Range 180 0C – 182

0C

pKa 14.13

IUPAC Name N-(hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamoyl)-4-

methylbenzene sulfonamide

Structure

SNH

NH

N

OO O

H3C

Description Gliclazide belongs to category of sulfonylurea compounds drugs.

Gliclazide is a type of second generation sulfonylurea.

Dose Adult - 20 – 40 mg t.d.s ; Children - 0.3 mg / kg t.d.s.

Solubility Very slightly soluble in water and alcohol, sparingly soluble in

dimethylformamide, slightly soluble in methanol.

Pharmacology Gliclazide is a second generation sulphonylurea which acts as a

hypoglycemic agent. It stimulates β cells of the islet of Langerhans

in the pancreas to release insulin. It also enhances peripheral

insulin sensitivity. Overall, it potentiates insulin release and

improves insulin dynamics.

Pharmacokinetics

Rapidly and well absorbed but may have wide inter- and intra-

individual variability. Peak plasma concentrations occur within 4-6

hours of oral administration. 94%, highly bound to plasma

http://en.wikipedia.org/wiki/Gram

http://en.wikipedia.org/wiki/Mole_(unit)

http://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclature



4.3 POLYETHYLENE GLYCOL24-28

Synonym Carbowax; Carbowax Sentry; Lipoxol; Lutrol E; PEG; Pluriol

E; polyoxyethylene glycol.

Chemical Name α-Hydro-ω-hydroxypoly(oxy-1,2-ethanediyl

Molecular Formula HOCH2(CH2OCH2)mCH2OH where m represents the average

number of oxyethylene groups.

Category Ointment base; plasticizer; solvent; suppository base; tablet and

capsule lubricant. Used to enhance the aqueous solubility or

dissolution characteristics of poorly soluble compounds by

making solid dispersions with an appropriate polyethylene

glycol.

Structural Formula

proteins. Extensively metabolized in the liver. Less than 1% of the

orally administered dose appears unchanged in the urine.

Routes of Administration Oral

Indications For the treatment of NIDDM in conjunction with diet and exercise

Drug Interactions Hyperglycemic action may be caused by chlorpromazine,

glucocorticoids, and progestogens. Its hypoglycemic action may be

potentiated by alcohol.

http://www.medicinescomplete.com/mc/excipients/current/1000310847.htm








Description Solid grades (PEG>1000) are white or off-white in color, and

range in consistency from pastes to waxy flakes. They have a

faint, sweet odor. Grades of PEG 6000 and above are available

as free-flowing milled powders. Liquid grades (PEG 200–600)

occur as clear, colorless or slightly yellow-colored, viscous

liquids. They have a slight but characteristic odor and a bitter,

slightly burning taste. PEG 600 can occur as a solid at ambient

temperatures.

Properties PEG 4000 PEG 6000 PEG 8000

Appearance (25℃) White flakes White flakes White flakes

pH value(1 %water Solution 5.0~7.0 5.0~7.0 5.0~7.0

Moisture % ≤1.0 ≤1.0 ≤1.0

Viscosity (mm2/s) 6.0~9.0 11.0~16.0 16.0~20.0

Average molecular weight

g/mol

3500~4500 5500~7500 750~8800

4.4 POLYVINYL PYRROLIDONE24,29

Synonym Polyvinyl pyrrolidone; Povidone; PVP

Chemical Name 1-Ethenyl-2 pyrrolidone homopolymer

Molecular Formula (C6H9NO)n

Category Disintegrant, dissolution enhancer, suspending agent, tablet binder.

Structural Formula



Description Povidone occurs as a fine, white to creamy white colored, odorless,

hygroscopic powder. Povidone with K-values equal to or lower than

30 are manufactured by spray drying and occur as spheres. Povidone

K 90 and higher K-values Povidone are manufactured by drum drying

and occur as plates.USP describes Povidone as a synthetic polymer

consisting of linear 1-vinyl-2-pyrrolidone groups, the differing degree

of polymerization of which results in polymers of a various molecular

weights. It is characterized by the viscosity.

Molecular Weight K- value Approximate Molecular Weight

12 2500

15 8000

17 10000

25 30000

30 50000

60 400000

90 1000000

120 3000000

Properties Povidone K 30 Povidone K 90

Clarity (10% in water) Clear Clear

Nitrogen content (%) 12.0-12.8 12.0-12.8

Water (Karl Fischer %) ≤ 5.0 ≤ 5.0

pH value (5% in water) 3.0-5.0 4.0-7.0

Applications Povidone is used as solubilizer in oral and parenteral formulations,

and to enhance the dissolution of poorly soluble drugs from solid

dosage forms. The solubility of poorly soluble active drugs may be

increased by mixing with the Povidone.

4.5 SODIUM STARCH GLYCOLATE24,30,31

Synonym Carboxymethyl starch, sodium salt; caboxymethylamylum

natricum, Explosol, Explotab, Glycolys, Primojel

Chemical Name Sodium carboxymtehyl starch

Molecular Weight 500000-11000000



Category Tablet and capsule disintegrant

Structural Formula

Description Sodium starch glycolate is a white or almost white free flowing

very hygroscopic powder. Under microscope it is seen to consist

of granules, irregularly shaped, ovoid or pear shaped, 30-100μm

in size. Very fine, white or off white, free flowing powder;

odorless or almost odorless.

Properties IP USP 26-NF21

pH 5.5 - 7.5 5.5 - 7.5

Loss on Drying, NMT % 10 10

Iron, NMT % 0.002 0.002

Heavy Metals, NMT % 0.002 0.002

Sodium Chloride, NMT % 10 7

Applications Sodium starch glycolate is widely used in oral pharmaceuticals as

a disintegrant in capsule and tablet formulations. It is commonly

used in tablets.

4.6 KYRON28,

31,32

Kyron is derived from the polymer cross-linked polyacrylic used in the pharmaceutical

industry to mask the taste of bitter medicine to achieve stability and drugs. It is white to off white

fine powder, swellable in water. KYRON T 314 is derived from cross linked polymer

of polycarboxylic acid as per USP/NF and has a K+ ionic form. It is a very high purity

polymer used in pharmaceutical formulation as a super fast disintegrant as well as

dissolution improver in solid dosage form like tablet, capsule, pellets etc. It is suitable for the

both wet granulation as well as direct compression system for tablet formulations. Different

grades of Kyron with specifications showed in table 4.1.

Table 4.1: Different grades of Kyron with specifications.



KYRON GRADES

Specification T-104 T-114 T-134 T-154 T-159 T-123

Pharmacopoeia In house In house Polacrilin

potassium

USP

Sodium

polystyrene

Sulphonate

USP

In house In house

Type Weak acid Weak acid Weak acid Strong acid Strong acid Weak base

Functionality -COO- -COO

- -COO

- -SO

-3 -SO

-3 Secondary

amine

Ionic Form Hydrogen Hydrogen Potassium Sodium Hydrogen Free base

Matrix Polyacrylic

copolymer

Polyacrylic

copolymer

Polyacrylic

copolymer

Polystyrene

copolymer

Polystyrene

copolymer

Polystyrene

copolymer

Moisture content

(%)

<10 <5 <10 <10 <10 <10

Appearance White to off

white free

flowing

powder

White to off

white free

flowing

powder

White to off

white free

flowing

powder

off White to

golden

yellow free

flowing

powder

off White to

golden

yellow free

flowing

powder

White to off

white free

flowing

powder

4.7 MANNITOL 1,24,27,28,33,34,35

Synonym Cordycepic acid, Emprove, manna sugar, D-mannite, peralitol.

Chemical Name D-mannitol

Molecular Formula C6H14O6

Molecular Weight 182.17

Category Diluent, plasticizer, sweetening agent, tablet and capsule diluent,

therapeutic agent, tonicity agent.

Structure

Description It is a hexahydric alcohol related to mannose and is isomeric with alcohol.

It occurs as a white, odorless, crystalline powder, or free flowing granules.

It has a sweet taste, approximately as sweet as glucose and half as sweet as

sucrose and imparts a cooling sensation in mouth.

Applications It is widely used as diluent in tablet formulations. It is not hygroscopic

hence can be used with moisture sensitive active ingredients. It may be



used with direct compression with the wet granulation.

Solubility 1 in 5.5 in water,1 in 18 in glycerine and 1 in 83 in ethanol at 20°C

4.8 ASPARTAME 1,24,27,28,36,37,38

Synonym Aspartamum, aspartyl phenylalanine methyl ester.

Chemical Name N-L-α-aspartyl-L-phenylalanine-1-methyl ester

Molecular Formula C14H18N2O5


Category Sweetening agent

Structure

Description It is an off white, almost odorless crystalline powder with an

intensely sweet taste.

Applications It enhances flavor systems and can be used to mask some unpleasant

taste characteristics. Approximate sweetening power is 180-200

times that of sucrose.

Solubility Slightly soluble in ethanol (95%), sparingly soluble in water. At 20°C

the solubility is 1% w/v at the isoelectric point pH 5.2.Solubility

increases at higher temperature and in acidic pH.

4.9 TALC 1,24,27,28

Synonym Hydrous magnesium calcium silicate, , magnesium hydrogen metasilicate, ,

purified French chalk, soapstone, steatite, talcum.

Chemical Name Talc

Formula Mg6(Si2O5)4(OH)4

Category Anticaking agent, glidants, tablet and capsule diluent, tablet and capsule

lubricant.



Description It is very fine, white, odorless, impalpable, unctuous, crystalline powder. It

adheres to skin and is soft to touch and free of grittiness.

Applications Used in oral solid dosage forms as lubricant and diluent. Talc is used as

lubricant in tablet formulations.

Solubility Practically insoluble in dilute acids and alkalis, organic solvents and water.

4.10 AVICEL 24,27,28

Synonym Avicel PH, cellulose gel, hellulosum microcrystallinum, crystalline

cellulose,E460,Emocel

Chemical Name Cellulose

Formula (C6H10O5)n~36000 where n~220

Category Adsorbent, suspending agent, tablet and capsule diluent, tablet

disintegrant.

Structural Formula

Description It is a purified, practically depolymerised cellulose that occurs as a

white, odorless, tasteless, crystalline powder composed of porous

particles.

Applications It is used as binder and diluent in tablet formulations. It can be used

with the wet granulation and direct compression. it also has

disintegrant properties that make it useful in tabletting

Solubility Slightly soluble in 5% sodium hydroxide solution, practically

insoluble in water, dilute acids and most organic solvents.

4.11 MAGNESIUM STEARATE 1,24,27,28,39,40

Synonym Dibasic magnesium stearate, magnesium distearate, magnesium

octadeconate, octadecanoic acid magnesium salt.

Chemical Name Ocatdecanoic acidmagnesium salt



Molecular Formula C36H70MgO4


Category Tablet and capsule lubricant

Structure

Description It is a very fine, light white, precipitated or milled, low bulk density,

having a faint odor of stearic acid and a characteristic taste.

Applications It is used as lubricant in tablet and capsule manufacture in

concentration of 0.25% and 5.0%w/w.

Solubility Practically insoluble in ethanol, ether, slightly soluble in warm

benzene and warm ethanol (95%), sparingly soluble in water.

4.12 CROSSCARMELLOSE SODIUM 1,24,27

Synonym Ac-di-sol, carmellose natricum conexum, cfrosslinked

carboxymethylcellulose sodium, explocel, modified cellulose gum,

Nymcel, Primellose.

Chemical Name Cellulose, carboxymethyl ether, sodium salt, crosslinked.

Category Tablet and capsule disintegrant

Structural Formula

Description It occurs as white, odorless, tasteless, granular powder. It is

hygroscopic after drying.



Applications It is used in oral formulations as disintegrant for capsules, tablets and

granules. It can be used with both direct compression and wet

granulation.

Solubility Insoluble in water, although crosscarmellose swells 4-8 times its

original volume on contact with water. Practically insoluble in

acetone, ethanol and toluene.



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