Clotrimazole

METHOD OF PREPARATION

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. Ensure that the particle size of the clotrimazole is very fine.

4. Using a water bath, slowly melt the fatty-acid base to approximately 40 to 45°C, depending upon the base being used. If cocoa butter is used, it should not be heated above approximately 36°C.

5. Sprinkle the clotrimazole powder onto the melted fatty-acid base while stirring.

6. Mix completely, remove from heat and allow to cool for a few minutes to become a little more viscous.

7. Ensure that the melt is uniformly mixed and begin pouring the mix into the suppository molds.

8. Cool and trim, if necessary.

9. Package and label.

Note: Depending upon the fatty-acid base used, it may be necessary to adjust the firmness of the suppository. This can be done by incorporating a small amount of a vegetable oil into the melted mixture.

PACKAGING

Package in tight, light-resistant containers.

LABELING

Keep out of reach of children. Use only as directed. Use at bedtime to minimize the occurrence of leakage.

STABILITY

A beyond-use date of 6 months can be used for this preparation.1

USE

Clotrimazole vaginal suppositories are used in the local treatment of vulvovaginal candidiasis when single-day treatment is desired.2

QUALITY CONTROL

Quality-control assessment can include weight, specific gravity, active-drug assay, color, texture of surface, appearance, feel, melting test, physical observation and physical stability.3

DISCUSSION

Clotrimazole 500-mg vaginal tablets were formerly marketed by Bayer Corporation as Mycelex-G 500. Clotrimazole is an effective broad-spectrum antifungal that exhibits fungicidal activity in vitro against Candida albicans and other species of the genus Candida. In addition to 500 mg of clotrimazole, the Mycelex-G 500 mg contained lactose, microcrystalline cellulose, lactic acid, cornstarch, crospovidone, calcium lactate, magnesium stearate, silicon dioxide and hydroxypropyl methylcellulose. The tablets were compressed vaginal tablets.2

Clotrimazole (C^sub 22^H^sub 17^ClN^sub 2^, MW 344.84) occurs as a white to pale yellow, crystalline powder. It melts at about 142°C with decomposition. It is practically insoluble in water but is freely soluble in acetone and in alcohol. It is an imidazole derivative, which is a synthetic azole antifungal agent. It is used in the treatment of oropharyngeal candidiasis, vulvovaginal candidiasis, dermatophytoses, superficial mycoses and cutaneous candidiasis. Dosage forms include oral as a lozenge; topical to the skin as a cream, lotion or solution; and intravaginal as a cream or tablet.4

Fattibase is a preblended suppository base that is used when a fatty-acid base is preferred. It occurs as an opaque white solid. It contains triglycerides derived from palm, palm kernel and coconut oils with self-emulsifying glyceryl monostearate and polyoxyl stearate as emulsifying and suspending agents. It is stable and has a bland taste and odor and a controlled melting range. It is widely used as a cocoa-butter replacement for suppositories, lipsticks and lip balms. It has a melting point between 35 and 37°C and a specific gravity of 0.890.5

Cocoa butter (theobroma oil) is a yellowish or white-colored brittle solid with a slight odor of cocoa. It is derived from natural sources and is composed primarily of triglycerides of saturated and unsaturated fatty acids. It melts at between 31 and 34°C, is freely soluble in chloroform and ether and is slightly soluble in 95% ethanol. Heating cocoa butter to a temperature greater than 36°C results in a lowering of the solidification point clue to its polymorphic nature and the formation of a metastable form. It should be stored at temperatures lower than 25°C. It is used as a suppository base and is also a major ingredient in chocolate.6

REFERENCES

1. US Pharmacopeial Convention, Inc. United States Pharmacopeia 26-National Formulary 21. Rockville, MD:US Pharmacopeial Convention, Inc; 2003; 2197-2201, 2555.

2. [No author listed.] Physicians' Desk Reference. 50th ed. Oradell, NJ:Medical Economics Company, Inc.; 1996:602.

3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of suppositories, troches, lollipops and sticks. IJPC 1999;3:56-57.

4. McEvoy GK. AHFS Drug Information-2003. Bethesda, MD:American Society of Health-System Pharmacists; 2003:3344-3347.

5. Fattibase [product information]. Minneapolis, MN:Paddock Laboratories, Inc.

6. Reilly WJ Jr. Pharmaceutical necessities. In: Gennaro AR, ed. Remington: The Science and Practice of Pharmacy. 19th ed. Easton, PA:Mack Publishing Company; 1995:1409.

Copyright International Journal of Pharmaceutical Compounding Nov/Dec 2003
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