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Suppositories are solid bodies of various weights and shapes, adapted for introduction into the rectal, vaginal, or urethral orifice of the human body. They usually melt, soften, or dissolve at body temperature. A suppository may act as a protectant or palliative to the local tissues at the point of introduction or as a carrier of therapeutic agents for systemic or local action. Suppository bases usually employed are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol.
The suppository base employed has a marked influence on the release of the active ingredient incorporated in it. While cocoa butter melts quickly at body temperature, it is immiscible with body fluids and this inhibits the diffusion of fat-soluble drugs to the affected sites. Polyethylene glycol is a suitable base for some antiseptics. In cases where systemic action is expected, it is preferable to incorporate the ionized rather than the nonionized form of the drug, in order to maximize bioavailability. Although nonionized drugs partition more readily out of water-miscible bases such as glycerinated gelatin and polyethylene glycol, the bases themselves tend to dissolve very slowly and thus retard release in this manner. Oleaginous vehicles such as cocoa butter are seldom used in vaginal preparations because of the nonabsorbable residue formed, while glycerinated gelatin is seldom used rectally because of its slow dissolution. Cocoa butter and its substitutes (Hard Fat) are superior for allaying irritation, as in preparations intended for treating internal hemorrhoids.
Cocoa Butter Suppositories
Suppositories having cocoa butter as the base may be made by means of incorporating the finely divided medicinal substance into the solid oil at room temperature and suitably shaping the resulting mass, or by working with the oil in the melted state and allowing the resulting suspension to cool in molds. A suitable quantity of hardening agents may be added to counteract the tendency of some medicaments such as chloral hydrate and phenol to soften the base. It is important that the finished suppository melt at body temperature.
The approximate weights of suppositories prepared with cocoa butter are given below. Suppositories prepared from other bases vary in weight and generally are heavier than the weights indicated here.
Rectal Suppositories for adults are tapered at one or both ends and usually weigh about 2 g each.
Vaginal Suppositories are usually globular or oviform and weigh about 5 g each. They are made from water-soluble or water-miscible vehicles such as polyethylene glycol or glycerinated gelatin.
Suppositories with cocoa butter base require storage in well-closed containers, preferably at a temperature below 30 (controlled room temperature).
Cocoa Butter Substitutes
Fat-type suppository bases can be produced from a variety of vegetable oils, such as coconut or palm kernel, which are modified by esterification, hydrogenation, and fractionation to obtain products of varying composition and melting temperatures (e.g., Hydrogenated Vegetable Oil and Hard Fat). These products can be so designed as to reduce rancidity. At the same time, desired characteristics such as narrow intervals between melting and solidification temperatures, and melting ranges to accommodate various formulation and climatic conditions, can be built in.
Glycerinated Gelatin Suppositories
Medicinal substances may be incorporated into glycerinated gelatin bases by addition of the prescribed quantities to a vehicle consisting of about 70 parts of glycerin, 20 parts of gelatin, and 10 parts of water.
Glycerinated gelatin suppositories require storage in tight containers, preferably at a temperature below 35.
Polyethylene Glycol–Base Suppositories
Several combinations of polyethylene glycols having melting temperatures that are above body temperature have been used as suppository bases. Inasmuch as release from these bases depends on dissolution rather than on melting, there are significantly fewer problems in preparation and storage than exist with melting-type vehicles. However, high concentrations of higher-molecular-weight polyethylene glycols may lengthen dissolution time, resulting in problems with retention. Labels on polyethylene glycol suppositories should contain directions that they be moistened with water before inserting. Although they can be stored without refrigeration, they should be packaged in tightly closed containers.
Surfactant Suppository Bases
Several nonionic surface-active agents closely related chemically to the polyethylene glycols can be used as suppository vehicles. Examples of such surfactants are polyoxyethylene sorbitan fatty acid esters and the polyoxyethylene stearates. These surfactants are used alone or in combination with other suppository vehicles to yield a wide range of melting temperatures and consistencies. One of the major advantages of such vehicles is their water-dispersibility. However, care must be taken with the use of surfactants, because they may either increase the rate of drug absorption or interact with drug molecules, causing a decrease in therapeutic activity.
Tableted Suppositories or Inserts
Vaginal suppositories occasionally are prepared by the compression of powdered materials into a suitable shape. They are prepared also by encapsulation in soft gelatin.