lecture suppo 49
TRANSCRIPT
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Production and Quality control
Dr. Theera Ritt irod, Tel. 01-5441686
E-mail : [email protected]
Suppositories
What will you know about ?What is Suppository ? + ClassificationAdvantages / Disadvantages
Composition of SuppositoryHow to make it ?How to test it ?Marketed Suppository
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SuppositoriesnSolid dosage forms
n 1. Active ingredient + 2. Base
+ 3. Additives
nOval, Bullet and Torpedo Shape
Bullet Shape
Advantages of Suppository1. Available for Pt. who can not swallow
Baby / Geriatric / or Pt. with Nausea +Vomiting
2. Drug with GI irritation problems3. Once daily use
4. For some drug which act locally
5. Avoid of Hepatic first pass metabolism
No..
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Disadvantages of SuppositorynUn-comfort
nVariation of Absorption
nIrritation for mucous
caused by some drugs or bases
Classification of Suppository
Via Routes of Administration :
1. Rectal S.2. Vaginal S./ Pessaries
3. Urethral S./ Bougies Not available
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Rectal SuppositorynBullet and Torpedo Shape
nDosage 1 g. for Baby & 2 g. for Adult
n For Local / Systemic action
Torpedo Shape
Vagina SuppositoriesnRound or Oval Shape
n3-4 g, D. 12 mm, L. 33-35 mm
nLocal action eg. antibacterial (Trichomonasspp.), contraceptive, anti-fungal
nVaginal tablet : Wet granulation productionused water soluble diluent (lactose)
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Type of SuppositoryClassification via Position of Action
nLocal action
n
Systemic action
Local Action SuppositorynSuup. will be melted and released drug.
Hemorrhoid (astringent, local anesthetic,
vasoconstrictor, anti-pruritic, antiseptic);Fungal infection; Bacterial infection;
Chronic inflammation; Constipation (Glycerin S.)
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Systemic Action SuppositorynAfter Rectal Insertion : 50-70% of Drug will be
absorbed in blood Circulation.
nMain Blood Circulation
1. Inferior haemorrhoidal vein
2. Middle HV. 3. Superior (upper) HV.
neg. anti-emitic, transquilizer, vasodilator,
analgesic, hypnotic, antipyretic, anti-asthmatic
Composition of Suppositories
nActive ingredients
nAdditivesnSuppository Base
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Active IngredientsLocal Actionnantifungal :
Clotrimazolenantibacterial :
Framycetin
nastringent : Bismuthsubgallatenanti-inflammation :
Hydrocortisone
Systemicn low bioavailability :
Propranolol HClnGI irritation :
Indomethacin
nanti-emetic :Domperidonenanalgesic :
Oxymorphone HCl
Pharmaceutical Additives
nTo Improve Quality
neg. plasticizer - Cetyl alcohol, Propylene glycol
antioxidant, dispersant - Surfactant,
Absorbance enhancer
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Ideal Suppository Base1. Melted all at 37 oC2. Release Drug3. Stable4. Non Absorb / Irritation
5. Compatible with Drugs6. Easy Handing and Economy Cost
Suppository Base1. Fatty / Oleaginous / Hydrophobic base)
1.1 Cocoa butter (Theobroma oil)
1.2 Semisynthesis glycerides
2. Hydrophilic base / water soluble Base
1. Glycero-gelatin base
2. Polyethylene glycol polymer
(PEG, Macrogols, Carbowax)
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Theobroma oilnNatural source / Melted at 30-36oC
semi-solid form, Yellow color
nConpose of glyceryl ester of fatty acid
eg. stearic, palmitic, oleic acid
Not suitable for tropical countries
Theobroma oil (Cont.)1. polymorphism and rancidity when Heatn 4 forms of theobroma crytal1. beta crystal (mp 34-36oC)
2. beta crystal* (mp 27o
C)3. alpha crystal* (mp 22oC)4. gamma crystal* (mp 18oC)
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Theobroma oil2. lubrication Process3. low melting point
after mixed with volatile oil, chloralhydrate, methyl paraben, phenol, camphor
4. Low Water absorbed
Theobr oma Oil as Suppo. Base
Non Solidified Theobr oma Oil
as Polymor phism
Theobroma Oil Suppo.
After kept in Refrigerater
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Semisynthesis glyceridesnVegetable oil + Hydrogenation
Unsaturated glyceride Sat. Gly.nFor BP & EP Call as Hard fat
Marketed Fatty BaseWitepsol; W-H 15, W-H 25, W-H 55Wacobee seriesSuuposire seriesMore data in Text or References
Fatty Base
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Semi-synthesis glycerides (Cont.)
1. No polymorphism2. Tolerance of oxidation3. Rapid Solidify4. Better Contraction5. Good looking
Advantages
Glycero-gelatin baseUSP: Glycerin 70%, Gelatin 20% + water 10%
BP : Glycerin 70%, Gelatin 14% + water 16%
n2 Types of gelatins
1. Gelatin A for acidic /cation drug
2. Gelatin B for alkaline / anion drug
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Glycero-gelatin base (Cont..)1. Laxative properties2. Many process3. Hygroscopic (glycerin)
4. Incompat. with tannic acid6. Overheat
: glycerin release toxic volatile
PEGn Synthetic productn eg. PEG 400, PEG 1500, PEG 4000n Advantages
1. mp ~ 40o
C2. Slowly melt and Slow release3. Ratio adjustment for suitable base4. Contraction, Not stricky5. High Viscosity
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PEGnDisadvantages
1. Incompat with bismuth salt,tannin, phenol, Reduce antimicrobial
activity, dissolved some plastic.
2. High MW. PEG Slow release
Pre-Formulation Consideration
1. Drug can be absorbed or not
2. Irritation : crystal, size reduction
3. Small particle : bioavailability
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Preparation of Suppositories1. Cold Process
nHand rolling used with Cocoa Butter base
nCompression mold used with
Cocoa butter base & PEG base
2. Hot Process / Fusion
nSoluble drugs
nInsoluble drugs
Calibration moldn Displacement value (D.V.)
Weight of Drug which occupied of one 1 of Base
n Calculation of D.V.
1. Make 6 suppo. (no drug)
then calculate the average wt. ( X = g)
2. Weigh drug for 3 suppo. = 3 x drug for 1 suppo.
3. Melted Mixed and cooling then poured in Mold
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Calibration mold (Cont.)4. Melt and Mixed then Poured in Mold5. Weigh and Calculate Average weight
n Ex X .base = 2.0 g X .Med.suppo. = 2.3 g1 suppo. Contain 0.5 g of DrugX .Med.sup - Drug = 2.3 - 0.5 = 1.8 g
Base 2-1.8 = 0.2 g Replace with Drug as 0.5 gBase 1 g Replace with Drug as 2.5 g (= D.V.)
oluble Drugn To Prevention of Precipitation
of Drug powder
1. Melt the Base in order of melting point2. Add Drug Powder after remove from water bat3. Pouring into Mold and Let it solidify
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Insoluble Drug1. Melt the Base in Casserole2. Grind & Mixed
with Viscous Melted base on slab
3 Warm again on Water bath4 Pour into Mold
5 Cooling wait for Solidify
Lubricant / Lubricating Agent
1. Fatty Base / Hydrophilic
nRx
Soft soap 10 mlGlycerol 10 ml
95%EtOH 50 ml
2. Water soluble Base
n Liquid paraffin
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Production and Quality Control
of Suppository
Dr. Theera Rittirod, June 2006
Pr oduction and QA of Suppository
1. Conventional Suppository
2. Hollow Type Suppository3. Quality control apparatus
4. In vitro / In vivo test (Animal par t)
5. Marketed Suppository
You must lear n about
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Many Steps in
suppositories production
Suppository Mold
Stainless Steel Mold
For Hollow Type
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For 6 suppositor iesStainless Steel Suppository Mold
Suppository Mold
Torpedo Shape
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Plastic Mold for Suppositories
Glasswar e and Pr eparation Tools
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Lubricant
Lubricating Agent
Cleaning and Lubr icating Mold
Cleaned and Lubr icated Mold
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Add Drug powder and Slowly mix
Cooling down Process
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early Congealed Medicated BaseContinuously pour into mold
Medicated Basewas poured in
Mold and wait forSolidify
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Do not forget some appar atus
Solidify Suppo. Star t from the edge
Solidification Pr ocess
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Warm the Spatula using Hot Plate
Remove excess par t via warmed Spatula
PEG base
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Glycerogelatin Base
Remove excess par t via warmed Spatula
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How to Remove Suppository
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Finished Suppositor ies
Theobr oma Oil as Suppo. Base
Non Solidified Theobr oma Oil
as Polymor phism
Theobroma Oil Suppo.
After kept in Refrigerater
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Non Solidified Theobroma Oil
Theobr oma oil + Non Lubr icated Mold
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Fatty Base Suppository
PEG Base Suppository