Suppositories, Inserts, Sticks

What is a suppository?

it is a solid dosage form in which one or more APIs are dispersed in a suitable base and molded into a suitable shape for insertion into body orifices to provide local or systemic effect.

Characteristics of suppositories:

Solid dosage forms

Insertion into body orifices

Melt or dissolved

Local or systemic effects

Acute or chronic disease

Various shapes & weights

Ideal Bases for suppositories must:

-be solid at room temp. but soft, melt, dissolve at body temperature

- non-irritating

-shouldn't react with APIs

-have a reasonable drug release rate

- be slowly and evenly melted

Bases for suppositories:

1. Fatty/oleaginous base

2. Water soluble & water miscible base

Fatty/Oleaginous suppository bases:

1. Cocoa butter

2. Hydrogenated fatty acids of vegetable oils

3. Commercial products

Cocoa butter (NF, National Formulary) characteristics:

AKA theobroma oil b/c it is fat oil from the roasted seed of Theobroma cacao

yellow at room temp., white =solid, chocolate like odor

melts btw 30 C- 36 C

polymorphism = several crystalline forms

solidifying agents (beeswax 4%) can be mixed with it

Hydrogenated fatty acids of vegetable oils are:

ex: palm kernal oil & cottonseed oil

a fat-based mixture that has glycerin & high molecular weight fatty acids (palmitic & stearic acids)

Stearic acids & palmitic acids vs. Glycerin:

stearic & palmitic acids: solid at RT

glycerin: liquid at RT

Commercial products:

Oleganious bases:

Fattibase = triglycerides from palm kernel oil

Wecobee bases= triglycerides from coconut oil

Witepsol bases= triglycerides of saturated fatty acids

Water Soluble and Water Miscible Bases:

Glycerinated gelatin
PEGs
Poloxamer (Pluronic)

Glycerinated gelatin is prepared by:

Glycerinated gelatin is mostly used in the preparation of:

Glycerinated gelatin has a tendency to:

Glycerinated gelatin may have a ______________ effect & may be __________ to the tissues.

dissolving granular gelatin (20%) in glycerin (70%) and adding a solution or suspension of the medication (10%).

vaginal suppositories & urethral suppositories

absorb moisture due to the hydroscopic nature of glycerin

dehydrating effect & irritating to the tissues

Polyethylene glycol (PEG) are polymers of__________ & _________ that _________ in body fluids.

Various combinations of PEGs may be combined by:

PEGs do not:

PEGs avoid:

ethylene oxide & water that dissolves

by fusion, to achieve a suppository base

melt at body temp. & do not leak from the orifice like cocoa butter does

moisture

Poloxamer (Pluronic) bases is a ____________________ base with a wide range of uses.

water-soluble base

Oil-soluble drug/oily base has a __________ drug release.

slow

Water-soluble drug/ oily base has a __________ drug release.

rapid

Oil soluble drug/water miscible base has a _________ drug release.

moderate

Water miscible drug/ water miscible base has a _____________ drug release.

moderate, depending on diffusion

I have a water soluble drug & a patient needs rapid release, what base to use?

Oily base

I have an oil soluble drug & a patient needs slow release, what base to use?

oily base

To prepare a urethral insert, which of the following is an ideal base?

A. Fattibase

B. Wecobee

C. Witepsol

D. Glycerinated gelatin

E. Cocoa butter

D. Glycerinated gelatin

To achieve rapid release, which of the following base(s) makes a soluble drug?

A.Cocoa butter
B. Palm kernal oil & cottonseed oil
C. Fattibase
D. Wecobee bases
E. Witepsol bases
F. Glycerinated gelatin
G. PGE base
H. Pluronic F68
I. Pluronic L44

A.
B.
C.
D.
E.

How to prepare a suppository?

Molding

Hand rolling & shaping

Steps to Molding suppositories:

1. Melt the bases using a hot water bath & stir in the APIs

2. Lubricate the molds using mineral oil

3. Pour drug compound into the molds , one or two castings

4. Allow to solidify , can use the fridge

5. Push out the suppositories & package them

6 Formulation variables for suppositories:

Particle sizes of the drugs

Solubility of the drugs

Physical state

Viscosity

Brittleness

Volume contraction = avoid production cavities (ex. air bubbles)

Particle sizes of the drugs affects:

Small particle size=

solubility

increases water solubility

Brittleness of APIs should be:

less than 30% , the base should be at lease 70%

To increase viscosity in suppositories you should use:

If viscosity is very high it will affect:

silica gel

the release rate

Calculations for suppositories:

total volume - drug volume= base volume

To get an accurate dose:

Calibrate the molds & avoid air bubbles

Weigh the base & drug

Melt, lubricate, pour

Check occupied volume

Check replacement factor & density factor

Special problems with preparation

For APIs that are difficult to be incorporated you should:

Volatile APIs should be incorporated:

Liquid APIs should be:

APIs incompatible with sodium barbital will:

use levigation with a small amount of melted base

at low temperatures

mixed with starch & easy to handle

crystallize from PEGs

Advantages of suppositories:

avoids first pass metabolism & chemical degradtion in GI tract

doesnt have an unpleasant taste or smell

has a rapid effect

good dosage form for irritating drugs & patients with special conditions

they usually come in large doses compared to oral

Disadvantages of suppositories:

Flexibility/administration convenience

Fluid flow is slower than SI, may affect dissolution

Absorption surface is smaller than SI

it leaves the site and ascend to the colon

its degraded by microflora for rectal suppositories

Cocoa butter suppositories should be stored:

Fridge = 2C-8C; less than 30 C

Glycerinated gelatin suppositories should be stored:

Below 8 C or at controlled room temp (20-25 C)

PEG suppositories should be stored:

At room temp