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1

Suppositories

Suppositories are solid dosage forms intended for insertion into body orifices (other than oral cavity) where they melt, soften or dissolve and exert localized or systemic effects

typically cylindrical with one or both ends tapered (1-2g)

2

Application of suppositories

1) carry drug for action at site of placement
E.g. emollients, astringents, antiseptics, local anaesthetics

2) Carry drug for systemic action
E.g. hypnotics, tranquilizers, antispasmodics, antipyretic, antiemetic

Suppositories are however primarily intended for treatment of constipation and haemorrhoids.

3

When are suppositories recommended

1) if person cannot swallow (eg vomit, child, elder,
unconscious).
2) Drug which are less suitable for oral administration.
(eg gastric discomfort, drug break down in GIT)

4

Advantage of suppositories

1) safe and painless
2) good for drug labile to GIT
3) Hepatic first pass elimination of high CL drug is
partially avoided
4) Small and large doses can be administered
5) Drug release profile can be controlled
6) LTC patients eg elder
7) Child
8) Simple administration
9) useful for pt who are N/V

5

Disadvantage of suppositories

1) strong feeling of aversion
2) slow onset (~30mins) and incomplete drug
adsorption
3) considerable intersubject and intrasubject variation
4) development of proctitis (inflammation of rectum)
5) Leakage

6

desirable properties of suppositories

1) Can be moulded by pouring or compression
2) Does not adhere to the mould
3) Stable if heated above its melting point
4) Compatible with drug
5) Non-toxic and non-irritating
6) Stable during storage
7) Releases drug at the desired rate
8) Does not leak out of orifice into which it is inserted
9) Keeps its shape when handled and easy to insert

7

Melting range of suppository

The melting range should be small enough to give rapid solidification after preparation, thus preventing agglomeration or sedimentation of suspended drug particles.

When the solidification rate is high, eg, rapid cooling is applied --> fissures in the suppository

The melting range should be sufficiently wide to permit easy preparation.

8

types of bases for suppository

1) Oleaginous bases
E.g. Fats and oils

2) Water-soluble or water-miscible bases
E.g. Glycerinated gelatin, PEGs

3) Emulsifying bases ( NOT EMULSION BASE)
E.g. Witepsol, Massupols

9

Oleaginous bases

Oleaginous bases
Also known as oily or fatty bases
Examples:
theobroma oil
hydrogenated fatty acids of vegetable oils
monoglycerides of high MW fatty acids

10

Solidification of bases shld

During solidification a suppository should exhibit enough volume contraction to permit removal from the mould or plastic former

11

Theobroma oil

1) oleaginous base
Also known as cocoa butter
Vegetable fat extracted from seeds of the cacao fruit (Theobroma Cacao)
It is composed of triglycerides of mainly oleic, stearic and palmitic acids
It occurs in three crystalline forms:
 ALPHA- Unstable; melting point of 22-24 ºC
 BETA - Stable; melting point of 34-36 ºC
 GAMMA - Unstable; melting point of 18 ºC

The use of low heat (40 to 50 ºC) and slow cooling are crucial for direct recrystallization to the BETA -crystals

Rapid cooling can cause suppositories to become brittle.

12

Disadvantage of theobroma oil base and the alternative

Melting process must be carefully monitored Theobroma oil tends to stick to the sides of the mould
Theobroma oil tends to soften in tropical climate and when substances such as volatile oils, phenol or chloral hydrate are added
These suppositories are more difficult to administer as theobroma oil melts on the finger tip
Theobroma oil tends to leak out of the orifice

Alternatives: Fattibase, Suppocire

13

substances that can soften theobroma oil

volatile oils,
phenol
chloral hydrate

14

Add what to theobroma oil to prevent softening

beewax

15

how to prevent theobroma oil from sticking on the mould

lubricating with soap solution (NOT OIL)

16

Water soluble or water miscible bases

These bases do not melt but dissolve slowly in the biological fluid
They are commonly prepared from glycerinated gelatin or polyethylene glycols

good for slow release

17

Glycerinated gelatin

Water soluble or water miscible bases

BP formula :
4 -18% gelatin + 70% glycerin + 12 -26 % water

USP formula :
20% gelatin + 70% glycerin + 30% water

Gelatin --> hardness (more rigid and longer acting)
glycerin --> hydrophilicity (so base can dissolve, can
incorporate hydrophile drug /
aq soln)

There are two types of gelatin:
Pharmagel A: Cationic and incompatible with anionic compounds
Pharmagel B: Anionic and incompatible with cationic compounds

18

Function of gelatin

Gelatin --> hardness (more rigid and longer acting)

19

types of gelatin

There are two types of gelatin:
Pharmagel A: Cationic and incompatible with anionic compounds
Pharmagel B: Anionic and incompatible with cationic compounds

20

function of glycering

glycerin --> hydrophilicity (so base can dissolve, can
incorporate hydrophile drug /
aq soln)

21

Advantage of glycerinated gelatin base

More prolonged drug release
---> Commonly used in pessaries

More easily inserted
--> Suitable for urethral administration

22

Disadvantage of glycerinated gelatin base

1) Hygroscopic (tend to absorb moisture)
--> Dehydrating effect on mucous membrane
(attract water from biological membrane giving rise to stinging sensation)
Prevent by moistening the suppositories

2) Support growth of mould

23

Polyethylene glycols

water soluble or water miscible bases
Also known as carbowaxes
General chemical formula: HOCH2(CH2OCH2)nCH2OH

A combination of PEGs (Macrogol) is often employed to obtain a base of desired hardness, melting point and water solubility

PEG less than 1000MW = liquid
more than 1500 MW = solid
1000 - 1500 MW = semi solid

24

characteristic
PEG 1000 96%
PEG 4000 4%

Base is soft and disintegrate rapidly

25

Characteristic
PEG 1000 75%
PEG 4000 25%

Base is harder and gives a slower drug release

26

Characteristic
PEG 1540 70%
PEG 6000 30%

base is much harder and can be used for drugs that lower the melting of the base

27

Characteristic
PEG 1540 30%
PEG 6000 60%
water 10%

Base includes water and is suitable for water soluble drug

28

PEG 6000 w PEG 1500
VS
PEG 1500

PEG 6000 w PEG 1500 have longer disintegration time

BUT is more brittle.

29

Advantage of PEG bases

Bases with higher melting point can be formulated Convenient storage
Easy insertion
No leakage from orifice
Bases of varying solubilities can be formulated Control of drug release

30

Disadvantage of PEG bases

 Incompatible with phenols
 Hygroscopic (drug that is prone to hydrolysis -= not
good)