Lecture Suppo 49

8/8/2019 Lecture Suppo 49

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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
mailto:[email protected]:[email protected]


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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

Lecture Suppo 49

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Transcript of Lecture Suppo 49