Suppository bases - Pharmaceutics - I B. Pharma 1st Semester

Suppository bases

Objective

At the end of this lecture, student will be able to:

·         Recall the suppository bases

·         Discuss types of suppository bases with examples

·         List the advantages and disadvantages of suppository bases

·         Discuss remedies to overcome any instabilities of suppository bases

Types of Suppository Bases

I.  Fatty Bases (Oleaginous Bases)

     Theobroma oil (Cocoa butter)

     Synthetic fats

II. Water Soluble and Water Miscible Bases

     Glycero-Gelatin base

     Soap-Glycerin Suppositories

III. Emulsifying Bases

     Witepsol

     Massa Esterium

     Massuppol

Fatty Bases (Oleaginous Bases)

Theobroma oil (Cocoa butter)

–      It is a yellowish-white solid with a chocolate-like odour.

–      It is a mixture of glyceryl esters of stearic, palmitic, oleic and other fatty acids.

Advantages of Theobroma oil (Cocoa butter)

1. It has a melting point range of 30 to 36 ⁰ C and hence it is solid at normal room temperatures but melts in the body.
2. It liquefies readily on warming and rapid setting on cooling.
3. Miscibility with many ingredients.
4. It is inert, non-toxic and non-irritant.

 Disadvantages of Theobroma oil (Cocoa butter)

      (a) Polymorphism

       (b) Adherence to mould

       (c) Softening point too low for hot climates

       (d) Melting point reduced by soluble ingredients

       (e) Slow deterioration during storage

       (f) Poor water absorbing capacity

       (g) Leakage from the body

Polymorphism

q  If cocoa butter is melted and cooled, it solidifies in different crystalline forms, depending on the temperature of melting, rate of cooling and size of the mass.

q  If melted at temperature not more than 36˚C and slowly cooled it forms stable beta crystals with normal melting point, but if over-heated it may produce, on cooling, unstable gamma crystals, which melt at about 15˚C, or a-crystals, melting at about 20˚C.

q  These unstable forms eventually return to the stable condition but this may take several days and meanwhile, the suppositories may not set at room temperature.

q  This lowering of the solidification point can also lead to sedimentation of suspended solids and thus variation in drug uniformity and delay in delivering product to the patient.

q  Consequently, great care must be taken to avoid over-heating the base when making theobroma oil suppositories.

Adherence to mould

q  Theobroma oil contract enough on cooling to loosen the suppositories in the mould, sticking may occur, particularly if the mould is worn. This is prevented by lubricating the mould before use.

Softening point too low for hot climates

q  To raise the softening point, white beeswax may be added to theobroma oil suppositories intended for use in tropical and subtropical countries.

Melting point reduced by soluble ingredients

q  Substances, such as chloral hydrate, that dissolve in theobroma oil, may lower its melting point to such an extent that the suppositories are too soft for use.

q  To restore the melting point, a controlled amount of white beeswax may be added.

Slow deterioration during storage

q  The slow chemical oxidation of the unsaturated glycerides present in the theobroma oil leading to rancidity.

Poor water absorbing capacity

q  The base is hydrophobic in nature and the water absorption capacity can be improved by the addition of emulsifying agents.

Leakage from the body

q  Sometimes melted base escapes from the rectum or vagina.

q  This is most troublesome with pessaries because of their larger size, and therefore, these are rarely made with theobroma oil.

Synthetic Fats

q  As a substitute of theobroma oil a number of hydrogenated oils, e.g. hydrogenated edible oil, arachis oil, coconut oil, palm kernel oil, mixture of oleic and stearic acids are recommended.

Disadvantages

1. They should not be cooled in refrigerator because they become brittle if cooled quickly. Certain additives like 0.05 %   polysorbate80 can be used as the remedy.
2. Their solidifying points are unaffected by overheating.
3. They have good resistance to oxidation because their unsaturated fatty acids have been reduced.
4. Their emulsifying and water absorbing capacities are good.
5. No mould lubricant is required.
6. They produce colorless, odourless and elegant suppositories.

Water Soluble and Water Miscible Bases          

Glycero-Gelatin base

–      This is a mixture of glycerol and water made into a stiff jelly by adding gelatin.

–      It is used for the preparation of jellies, suppositories and pessaries.

–      The stiffness of the mass depends upon the proportion of gelatin used which is adjusted according to its use.

–      The base being hydrophilic in nature, slowly dissolves in the aqueous secretions and provide a slow continuous release of medicament.

–      Glycerogelatin base is well suited for suppositories containing belladonna extract, boric acid, chloral hydrate, bromides, iodides, iodoform, opium, etc.

Types of Gelatins

q  Depending upon the compatibility of the drugs used, a suitable type of gelatin is selected for the purpose.

q  Two types of gelatins are used as suppository base.

1. Type-A or Pharmagel-A

–      Which is made by acid hydrolysis (has isoelectric point between 7 to 9 and on the acid side of the range behaves as a cationic agent, being most effective at pH 7 to 8.) is used for acidic drugs.

2. Type-B or Pharmagel-B

–      Which is prepared by alkaline hydrolysis (having an isoelectric point between 4.7 to 5 and on the alkaline side of the range behaves as an anionic agent, being most effective at pH 7 to 8 is used for alkaline drugs.

3. Glycerogelatin base suppositories are less commonly used than the fatty base suppositories.

Disadvantages

1.       Glycerol exerts laxative action.

2.       They are more difficult to prepare and handle.

3.       Their solution time depends on the content and quality of the gelatin and the age of the base.

4.       They are hygroscopic, hence must be carefully stored.

5.       Gelatin is incompatible with drugs those precipitate with the protein e.g. tannic acid, ferric chloride, gallic acid, etc.

6.       As the gelatin is obtained from animal source, more prone to microbial contamination.

Soap-Glycerin Suppositories

q  In this case gelatin is replaced with curd soap or sodium stearate which makes the glycerin sufficiently hard for suppositories and a large quantity of glycerin upto 95% of the mass can be incorporated.

q  Further the soap helps in the evacuation of glycerin.

q  The soap glycerin suppositories have the disadvantage that they are very hygroscopic, therefore they must be protected from atmosphere and wrapped in waxed paper or tin foil.

Emulsifying Bases

q  These are synthetic bases and a number of proprietary bases of very good quality are available, few of which are described below:

1.       Witepsol

                They consist of triglycerides of saturated vegetable acids (chain length C₁₂ to C₁₈) with varying proportions of partial esters.

2.       Massa Esterium

                This is another range of bases, consisting of a mixture of di-, tri- and mono- glycerides of saturated fatty acids with chain lengths of C₁₁ to C₁₇.

3.       Massuppol

                It consists of glyceryl esters mainly of lauric acid, to which a small amount of glyceryl monostearate has been added to improve its water absorbing capacity.

Advantages

1. Overheating does not alter the physical characteristics.
2. They do not stick to the mould.
3.  They do not require previous lubrication of the mould.
4. They solidify rapidly.
5. They are less liable to get rancid.
6. They can absorb fairly large amount of aqueous liquids.

Summary

Disadvantages of Theobroma oil (Cocoa butter)

(a) Polymorphism

(b) Adherence to mould

(c) Softening point too low for hot climates

(d) Melting point reduced by soluble ingredients

(e) Slow deterioration during storage

(f) Poor water absorbing capacity

(g) Leakage from the body