Q:Do you have a formulation for neomycin 15-mg and hydrocortisone 50-mg suppositories?
A:Hydrogenated vegetable oils, such as fatty acid blend (Fatty-blend, Gallipot; Fattibase, Paddock) and cocoa butter (theobroma oil), melt at body temperature to release a drug and are the vehicles usually selected for this type of suppository. They tend to be less irritating to sensitive tissue than polyethylene glycol-based suppository material, although they can "leak" slightly, especially when an injured anus is involved.
Hydrocortisone and neomycin sulfate exhibit poor vegetable oil solubility, and therefore they should release well from the hydrogenated vegetable oil without absorption competition. Cocoa butter is used little because it exhibits polymorphism, making temperature control more important. The fatty acid blends do not exhibit this drawback.
Hydrocortisone USP is a white to practically white, odorless, crystalline powder that melts at ~215˚C with decomposition. Because the fatty acid blend suppository vehicles melt at ~55˚C to 60˚C, hydrocortisone should be thermostabile during the preparation of this formulation. Systemic effects can result from topical application, particularly when applied to broken/bleeding skin. Biological half-life is ~8 to 12 hours.
USP allows neomycin sulfate, which is the sulfate salt of the "[aminoglycoside] antibacterial substance produced by the growth of Streptomyces fradiae Waksman (Fam Streptomycetaceae), or a mixture of 2 or more such salts. It has a potency equivalent to not less than 600 μg of neomycin per mg, calculated on the dried basis." (One gram of salt contains not less than 600 mg neomycin.) It may be advisable to discuss with the prescriber whether "neomycin 15 mg" was intended to indicate equivalent potency or quantity of neomycin sulfate. The answer may influence the formulation calculations.
Calculation of density factor when extemporaneously compounding suppositories can be a critical issue. In this case, fatty acid blend has density similar to cocoa butter, and available references for displacement factors of ingredients relative to cocoa butter are applicable. If references are not available, several alternative generalities or "rules of thumb" can apply. First, assuming that the suppository mold has a 2.0-cc capacity, a "blank" fatty acid blend suppository would weigh approximately 1.82 g. (Pharmacists always should tare the suppository molds.) This prescription is for 15 mg of neomycin (sulfate) and 50 mg of hydrocortisone USP per suppository. To provide an elegant preparation, an additional 1% (~0.018 g) of silica gel can be included as a suspending agent. Therefore, this preparation will contain 0.083 g of "nonsuppository base" material.
Generally, when a suppository preparation includes less than 5% of nonvehicle material, the density factor can be assumed to be 1 for calculation purposes. Therefore, each suppository would contain hydrocortisone USP 0.050 g, neomycin sulfate 0.015 g, silica gel 0.018 g, and fatty acid blend 1.74 g. Each item should be increased by 5% to 10% to allow for processing losses. An alternative method, to allow for density factor when formulating suppositories, is the "70% Rule." It can be applied where dose is not criticaleg, where the active ingredient has a wide therapeutic index or where clinical effect is easily observed. In this case, the density factor for a particular ingredient in a particular vehicle is considered to be 0.7, and calculations are carried out accordingly. More precise determination of density factor can be obtained experimentally by comparing the ratio of average weights of several "blank" suppositories to average weights of several "nonhomogeneous" suppositories compounded by partly filling each mold cavity with vehicle, adding a specific, measured amount of the medicament(s), and then adding sufficient vehicle to fill the cavity.
Mr. Erickson is director of professional affairs at Gallipot Inc.
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