Suppositories

Production and Quality control

Dr. Theera Rittirod, Tel. 01-5441686

E-mail : theera@kku.ac.th

What will you know about ?

What is Suppository ? + Classification
Advantages / Disadvantages
Composition of Suppository
How to make it ?
How to test it ?
Marketed Suppository
 Suppositories
nSolid dosage forms
n 1. Active ingredient + 2. Base
+ 3. Additives
nOval, Bullet and Torpedo Shape

Bullet Shape

Advantages of Suppository
1. Available for Pt. who can not swallow
Baby / Geriatric / or Pt. with Nausea +
Vomiting
2. Drug with GI irritation problems No…..
3. Once daily use
4. For some drug which act locally
5. Avoid of Hepatic first pass metabolism
Disadvantages of Suppository
nUn-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
 Rectal Suppository
nBullet and Torpedo Shape
nDosage 1 g. for Baby & 2 g. for Adult
n For Local / Systemic action

Torpedo Shape

Vagina Suppositories
n Round or Oval Shape
n 3-4 g, D. 12 mm, L. 33-35 mm
n Local action eg. antibacterial (Trichomonas
spp.), contraceptive, anti-fungal
n Vaginal tablet : Wet granulation production
used water soluble diluent (lactose)
 Type of Suppository
Classification via Position of Action
nLocal action
nSystemic action

Local Action Suppository

n Suup. will be melted and released drug.
Hemorrhoid (astringent, local anesthetic,
vasoconstrictor, anti-pruritic, antiseptic);
Fungal infection; Bacterial infection;
Chronic inflammation; Constipation (Glycerin S.)
Systemic Action Suppository
n After Rectal Insertion : 50-70% of Drug will be
absorbed in blood Circulation.
n Main Blood Circulation
1. Inferior haemorrhoidal vein
2. Middle HV. 3. Superior (upper) HV.
n eg. anti-emitic, transquilizer, vasodilator,
analgesic, hypnotic, antipyretic, anti-asthmatic

Composition of Suppositories
nActive ingredients
nAdditives
nSuppository Base
 Active Ingredients
Local Action Systemic
n antifungal : n low bioavailability :
Clotrimazole Propranolol HCl
n antibacterial : n GI irritation :
Framycetin Indomethacin
n astringent : Bismuth n anti-emetic :
subgallate Domperidone
n anti-inflammation : n analgesic :
Hydrocortisone Oxymorphone HCl

Pharmaceutical Additives
nTo Improve Quality
neg. plasticizer - Cetyl alcohol, Propylene glycol
antioxidant, dispersant - Surfactant,
Absorbance enhancer
Ideal Suppository Base
1. Melted all at 37 oC
2. Release Drug
3. Stable
4. Non Absorb / Irritation
5. Compatible with Drugs
6. Easy Handing and Economy Cost

Suppository Base
1. 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)
 Theobroma oil
nNatural 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 Heat
n 4 forms of theobroma crytal
1. beta crystal (mp 34-36oC)
2. beta’ crystal* (mp 27oC)
3. alpha crystal* (mp 22oC)
4. gamma crystal* (mp 18oC)
 Theobroma oil
2. lubrication Process
3. low melting point
after mixed with volatile oil, chloral
hydrate, methyl paraben, phenol, camphor
4. Low Water absorbed

Theobroma Oil as Suppo. Base

Theobroma Oil Suppo.
After kept in Refrigerater

Non Solidified Theobroma Oil

as Polymorphism
 Semisynthesis glycerides
n Vegetable oil + Hydrogenation
Unsaturated glyceride Sat. Gly.
n For BP & EP Call as Hard fat

Marketed Fatty Base

Witepsol; W-H 15, W-H 25, W-H 55
Wacobee series
Suuposire series
More data in Text or References

Fatty Base
Semi-synthesis glycerides (Cont.)
Advantages
1. No polymorphism
2. Tolerance of oxidation
3. Rapid Solidify
4. Better Contraction
5. Good looking

Glycero-gelatin base
USP: 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
Glycero-gelatin base (Cont..)
1. Laxative properties
2. Many process
3. Hygroscopic (glycerin)
4. Incompat. with tannic acid
6. Overheat
: glycerin release toxic volatile

PEG
n Synthetic product
n eg. PEG 400, PEG 1500, PEG 4000
n Advantages
1. mp ~ 40 oC
2. Slowly melt and Slow release
3. Ratio adjustment for suitable base
4. Contraction, Not stricky
5. High Viscosity
 PEG
nDisadvantages
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
Preparation of Suppositories
1. Cold Process
n Hand rolling used with Cocoa Butter base
n Compression mold used with
Cocoa butter base & PEG base
2. Hot Process / Fusion
n Soluble drugs
n Insoluble drugs

Calibration mold
n 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
Calibration mold (Cont.)
4. Melt and Mixed then Poured in Mold
5. Weigh and Calculate Average weight

n Ex X .base = 2.0 g X .Med.suppo. = 2.3 g

1 suppo. Contain 0.5 g of Drug
X .Med.sup - Drug = 2.3 - 0.5 = 1.8 g

Base 2-1.8 = 0.2 g Replace with Drug as 0.5 g

Base 1g Replace with Drug as 2.5 g (= D.V.)

Soluble Drug
n To Prevention of Precipitation
of Drug powder
1. Melt the Base in order of melting point
2. Add Drug Powder after remove from water bat
3. Pouring into Mold and Let it solidify
Insoluble Drug
1. Melt the Base in Casserole
2. Grind & Mixed
with Viscous Melted base on slab
3 Warm again on Water bath
4 Pour into Mold
5 Cooling wait for Solidify

Lubricant / Lubricating Agent

1. Fatty Base / Hydrophilic 2. Water soluble Base
n Rx n Liquid paraffin
Soft soap 10 ml
Glycerol 10 ml
95%EtOH 50 ml
Production and Quality Control
of Suppository

Dr. Theera Rittirod, June 2006

Production and QA of Suppository

You must learn about
1. Conventional Suppository
2. Hollow Type Suppository
3. Quality control apparatus
4. In vitro / In vivo test (Animal part)
5. Marketed Suppository
 Many Steps in
suppositories production

Suppository Mold
For Hollow Type

Stainless Steel Mold

 Stainless Steel Suppository Mold
For 6 suppositories

Suppository Mold

Torpedo Shape
 Plastic Mold for Suppositories

Glassware and Preparation Tools

Cleaning and Lubricating Mold

Lubricant
Lubricating Agent

Cleaned and Lubricated Mold

 (Calculate more 20 %)
Weigh all Ingredients for the formula
(Calculate 10 to obtain 6 Suppo.)

Melt the Base in Casserole

Add Drug powder and Slowly mix

Cooling down Process

Nearly Congealed Medicated Base
Continuously pour into mold

Medicated Base
was poured in
Mold and wait for
Solidify
Do not forget some apparatus

Solidification Process
Solidify Suppo. Start from the edge
 Warm the Spatula using Hot Plate

Remove excess part via warmed Spatula

PEG base
Remove excess part via warmed Spatula
Glycerogelatin Base
How to Remove Suppository
 Finished Suppositories

Theobroma Oil as Suppo. Base

Theobroma Oil Suppo.
After kept in Refrigerater

Non Solidified Theobroma Oil

as Polymorphism
 Non Solidified Theobroma Oil

Theobroma oil + Non Lubricated Mold

Fatty Base Suppository

PEG Base Suppository