Hard Fat

Category

Lubricants; Coating materials; Humectants; Suppository bases

Molecular Formula

C8H17COOH~C18H37COOH

Grade

Pharmceutical Excipients

Description

A white or almost white, practically odorless, waxy, brittle mass. When heated to 50℃ it melts to give a colorless or slightly yellowish liquid.

UNII

NA

Chemical Name

Hard fat triglyceride esters

CAS Number

91744-42-2

Synonyms

Adeps neutralis; adeps solidus; Akosoft; Akosol; Cremao CS-34; Cremao CS-36; hydrogenated vegetable glycerides; Massupol; Novata; semisynthetic glycerides; Suppocire; Wecobee; Witepsol.

Administration route

Topical; Transdermal; Rectal Urethral

Dosage Form

Rectal and Vaginal Preparations

Stability and Storage Conditions

Hard fat suppository bases are fairly stable toward oxidation and hydrolysis, with the iodine value being a measure of their resistance to oxidation and rancidity. Water content is usually low and deterioration due to hygroscopicity rarely occurs. Melting characteristics, hardness, and drug-release profiles alter with time, and the melting point may rise by more than 1.0℃ after storage for several months. Owing to the complexity of bases,elucidation of the mechanisms that induce these changes on aging is difficult.

Source and Preparation

The most common method of manufacture involves the hydrolysis of natural vegetable oils such as coconut or palm kernel oil, followed by fractional distillation of the free fatty acids produced. The C8 to C18 fractions are then hydrogenated and reesterified under controlled conditions with glycerin to form a mixture of tri-,di-, and monoglycerides of the required characteristics and hydroxyl value. This process is used for Witepsol. In an alternative procedure, coconut or palm kernel oil is directly hydrogenated and then subjected to an interesterification either with itself or with glycerin to form a mixture of tri-, di-, and monoglycerides of the required characteristics and hydroxyl value, e.g. Suppocire.

Applications

This product can be used as lubricant, matrix, coating material and humectants. The basic use of stearinous suppository base or semi-synthetic glycerin fatty acid esters is as a carrier for rectal or vaginal preparations of some drugs to produce local effects or achieve systemic absorption.

Safety

Suppository bases are generally regarded as nontoxic and nonirritant materials when used in rectal formulations. However, animal studies have suggested that some bases, particularly those types with a high hydroxyl value, may be irritant to the rectal mucosa.

Incompatibilities

Incompatibilities with suppository bases are not now extensively reported in the literature. The occurrence of a chemical reaction between a hard fat suppository base and a drug is relatively rare, but any potential for such a reaction may be indicated by the magnitude of the hydroxyl value of the base. The risk of hydrolysis of aspirin, for example, may be reduced by the use of a base with a low hydroxyl value (<5) and, additionally, by minimization of the water content of both the base and the aspirin. There is evidence that aminophylline reacts with the glycerides in some hard fat bases to form diamides. On aging or exposure to elevated temperatures, degradation is accompanied by hardening and suppositories tend to exhibit a marked increase in melting point. The ethylenediamine content is also reduced.Certain fat-soluble medications, such as chloral hydrate, may depress the melting point when incorporated into a base. Similarly, when large amounts of an active substance, either solid or liquid, have to be dispersed into a base, the rheological characteristics of the resultant suppository may be changed, with concomitant effects on release and absorption. Careful selection of bases or the inclusion of additives may therefore be necessary.