Suppositories and pessaries

37


Suppositories and pessaries




Study Points



image Ideal suppository bases


image Types of base


image Suppository moulds and mould calibration


image Displacement values


image Methods of preparation of suppositories and pessaries


image Containers, labelling and patient advice for suppositories and pessaries



Introduction


Drug administration by the rectum can be used for local or systemic action. Dosage forms used include suppositories, rectal tablets, capsules, ointments and enemas. Vaginal administration can be for both local and systemic action, using pessaries and vaginal formulations of tablets, capsules, solutions, sprays, creams, ointments and foams. This chapter gives details of how suppositories and pessaries are prepared extemporaneously, the substances and equipment used in their preparation, the calculations involved and patient advice.


Suppositories and pessaries are drug delivery systems where the drug is incorporated into an inert vehicle; base. Suppositories are formed by melting the base, incorporating the drug and then allowing them to set in a suitable metal or plastic mould.



Suppository bases


A number of criteria can be identified as desirable in an ideal base, including:



No base meets all these requirements, so a compromise is required. There are two groups of materials, the fatty bases and the water-soluble or water-miscible bases.



The fatty bases



Theobroma oil


Theobroma oil, a naturally occurring oil, has a melting point range of 30–36°C and so readily melts in the body. It liquefies easily on heating but sets rapidly when cooled. It is also bland, therefore no irritation occurs. The main technical difficulty is the ease with which lower melting point polymorphic forms of theobroma oil are formed. The stable β-form has a melting point of 34.5°C and forms after melting at 36°C and slowly cooling. If it is overheated, the unstable α-form (melting point 23°C) and γ-form (melting point 19°C) are produced. These forms will eventually return to the stable form but this may take several days. The melting point is a problem in hot climates and can be reduced further by the addition of a soluble drug. The latter effect can be counteracted by adding beeswax (up to 10%), but care must be taken not to raise the melting point too high, as the suppository would not melt in the rectum. In addition, theobroma oil is prone to oxidation. Theobroma oil shrinks only slightly on cooling and therefore tends to stick to the suppository mould; thus requiring a mould lubricant.



Synthetic fats


These are hydrogenated vegetable oils. Synthetic fatty bases have many of the advantages but there are a few potential problems:



Further information on these bases can be found in the Pharmaceutical Codex (1994).



Water-soluble and water-miscible bases



Glycerol-gelatin bases


These bases are a mixture of glycerol and water stiffened with gelatin. The commonest is Glycerol Suppositories Base BP, which has 14% weight in weight (w/w) gelatin, and 70% w/w glycerol. In hot climates, the gelatin content can be increased to 18% w/w. Pharmaceutical grade gelatin is a pathogen-free, purified protein produced by the hydrolysis of the collagenous tissue, such as skins and bones, of animals. Some people may have ethical problems with the use of such a product.


Two types of gelatin are used for pharmaceutical purposes: Type A, which is prepared by acid hydrolysis and is cationic, and Type B, which is prepared by alkaline hydrolysis and is anionic. Type A is compatible with substances such as boric acid and lactic acid, while Type B is compatible with substances like ichthammol and zinc oxide. The ‘jelly strength’ or ‘bloom strength’ of gelatin is important, particularly when it is used in the preparation of suppositories or pessaries.


Glycerol-gelatin bases have a physiological effect which can cause rectal irritation because of the small amount of liquid present. As they dissolve in the mucous secretions of the rectum, osmosis occurs producing a laxative effect. The solution time depends on the content, quality of the gelatin and the age of the suppository. Because of the water content, microbial contamination is more likely than with the fatty bases. Preservatives may be added to the product, but can lead to problems of incompatibility. In addition, glycol-gelatin bases are hygroscopic and therefore require careful storage.



Macrogols


These polyethylene glycols can be blended together to produce suppository bases with varying melting points, dissolution rates and physical characteristics. Drug release depends on the base dissolving rather than melting (the melting point is often around 50°C). Higher proportions of high molecular weight polymers produce preparations which release the drug slowly and are also brittle. Less brittle products which release the drug more readily can be prepared by mixing high polymers with medium and low polymers. Details of combinations which are used are found in the Pharmaceutical Codex (1994). Macrogols have several properties which make them useful as suppository bases including the absence of a physiological effect, are not prone to microbial contamination and have a high water-absorbing capacity. As they dissolve, a viscous solution is produced which means there is less likelihood of leakage from the body.


The macrogol bases have a number of disadvantages. They are hygroscopic, which means they must be carefully stored, and this could lead to irritation of the rectal mucosa. This latter disadvantage can be alleviated by dipping the suppository in water prior to insertion. They become brittle if cooled too quickly and also may become brittle on storage. Incompatibility with several drugs and packaging materials, e.g. benzocaine and plastic, may limit their use. In addition, crystal growth occurs, with some drugs causing irritation to the rectal mucosa and may prolong dissolution times.



Preparation of suppositories


Suppositories are made using a metal or plastic suppository mould. Traditional metal moulds (Fig. 37.1) are in two halves which are clamped together with a screw. The internal surface is normally plated to ensure that the suppositories have a smooth surface.



Before use the mould should be completely cleaned by washing carefully in warm, soapy water and thoroughly dried, taking care not to scratch the internal surface. The exact shape can vary slightly from one mould to another.



Preparation of suppositories containing an active ingredient which is insoluble in the base


The bases used, most commonly, for extemporaneous preparation of suppositories and pessaries are the synthetic fats and glycerol-gelatin base.



1. When calculating the quantity of ingredients it is necessary to prepare excess due to unavoidable wastage. Usually, an excess of two should be calculated for, e.g. to prepare 12 suppositories, calculate for 14.


2. The mould should be carefully washed and dried.


3. Ensure that the two halves fit together correctly. This is necessary to ensure that there is no leakage of material. They usually have code letters and/or numbers which should match.


4. For some bases the mould will need to be lubricated. The lubricants are given in Table 37.1.


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Jun 24, 2016 | Posted by in PHARMACY | Comments Off on Suppositories and pessaries

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