OUTLINE
Desirable Properties of Suppository Bases
Classification and Characteristics of Suppository Bases
I. DEFINITIONS
A. Suppositories: “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” (1).—USP
(See the section on definitions and nomenclature in Chapter 31, Suppositories, for a discussion of proposed nomenclature changes for suppository dosage forms.)
B. According to the USP, there are six general classes of suppository bases (1):
1. Cocoa butter
2. Cocoa butter substitutes
3. Glycerinated gelatin
4. Polyethylene glycol base
5. Surfactant base
6. Tableted suppositories or inserts
C. According to Allen (2), four classifications of suppository bases are usually described, based on their melting or dissolution properties:
1. The first is the fat- or oil-type base, which must melt at body temperature to release its medication.
2. The second is the glycerin-gelatin base suppository, which absorbs water and dissolves to release its medication.
3. The third is the water-soluble or water-miscible polymers and surface-active agents.
4. The fourth is a group of bases containing disintegrating agents, natural gums, effervescent agents, collagen, fibrin, hydrogels, etc.
II. DESIRABLE PROPERTIES OF SUPPOSITORY BASES
A. Chemically and physically stable under normal conditions of use and storage
B. Nonreactive and compatible with a wide variety of drugs and auxiliary agents
C. Free from objectionable odor
D. An aesthetically appealing appearance
E. Nontoxic, nonsensitizing, and nonirritating to sensitive tissues
F. Expansion–contraction characteristics such that it shrinks just enough on cooling so that it releases easily from suppository molds
G. Melts or dissolves in the intended body orifice to release the drug
H. Nonbinding of drugs
I. Mixes with or absorbs some water
J. Viscosity low enough when melted to pour easily but high enough to suspend particles of solid drug
K. Some wetting and/or emulsifying properties so that it will spread, disperse in, and release the active ingredient(s) at the administration site
III. CLASSIFICATION AND CHARACTERISTICS OF SUPPOSITORY BASES
The six general classes of suppository bases identified by the USP (1) are described here. The descriptions and solubilities for bases or base ingredient are a composite of information from Remington’s The Science and Practice of Pharmacy (3), the Handbook of Pharmaceutical Excipients (4), official monographs in the USP–NF (5,6), and other references as cited. Additional information on each agent, including references to original research journal articles, can be found in the Handbook of Pharmaceutical Excipients.
A. Cocoa Butter NF
1. Description
a. Cocoa butter is the fat from the seeds of Theobroma cacao (chocolate beans). It may be obtained either by expressing the oil from the seeds or by solvent extraction. Chemically, it is a mixture of triglycerides of saturated and unsaturated fatty acids, primarily stearic, palmitic, oleic, lauric, and linoleic.
b. It is a mellow, yellowish solid with a mild odor and bland taste. It is a solid at room temperature but melts at body temperature with a melting point of 31° to 34°C. The specific gravity of the melt is 0.858 to 0.864. It is available as bars or grated.
c. Cocoa butter does not contain emulsifiers, so it does not absorb significant amounts of water. Tween 61, a tan, waxy, solid, nonionic surfactant, can be added (5% to 10%) to increase the water absorption properties of cocoa butter (7), although addition of nonionic surfactants reportedly gives suppositories with poor stability on storage (8).
2. Solubility: It is insoluble in water, slightly soluble in alcohol, and soluble in boiling absolute alcohol.
3. Incompatibilities: The most notable compatibility problem of cocoa butter is the lowering of its melting point with drugs such as chloral hydrate, phenol, and thymol. This can be overcome by the addition of 4% to 6% white wax or 18% to 28% cetyl esters wax, but determining the exact amount that will give an appropriate melting temperature can be difficult and time consuming (9). A group of successful formulas for chloral hydrate suppositories, including some made with cocoa butter, has been published (10).
4. Advantages
a. Cocoa butter is bland and nonirritating to sensitive membrane tissues. It is also an excellent emollient and is used alone or in topical skin products for this property.
b. Because cocoa butter has a variety of uses besides suppository making, it is readily available in many pharmacies. It is also one base that can be used for hand-molding suppositories; no special molds or equipment are needed. These two properties make this base useful when a custom suppository is needed on an emergency basis.
c. Cocoa butter has a solidification temperature 12° to 13° below its melting point. This makes it easy to pour suppositories before the base solidifies (7).
d. Cocoa butter is available in grated form. This eliminates one time-consuming aspect of compounding suppositories.
5. Disadvantages
a. Because of its relatively low melting point, cocoa butter and its suppositories must be stored either at controlled room temperature or in the refrigerator. It is recommended that storage temperature not exceed 25°C.
b. Cocoa butter has the further disadvantage of existing in several polymorphic forms that have even lower melting points: 18°, 24°, and 28°C to 31°C (7). Cocoa butter suppositories are therefore somewhat difficult to make by fusion.
(1) Cocoa butter can very easily be overheated and, when it is, it may solidify as one of the lower melting polymorphs. This means that the suppositories do not set up properly, and they may melt at room temperature, or the suppositories may liquefy when handled by the patient during insertion.
(2) When melting cocoa butter, a warm-water bath should be used and the temperature should be controlled closely. When melted, the base should have a slightly opalescent appearance. Once the molten cocoa butter has completely turned to a clear, straw-colored liquid, the desired melting point has been exceeded; all the stable β-crystals have been destroyed, and the suppositories will melt at a temperature below the desired 34°C to 35°C. A sample procedure with appropriate temperatures for the warm-water bath and the cocoa butter melt is given with example 31.1 in Chapter 31, Suppositories.
c.
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