Q:Do you have a formulation for neomycin 15-mg and hydrocortisone50-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 andare the vehicles usually selected for this type of suppository. Theytend 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 oilsolubility, and therefore they should release well from the hydrogenatedvegetable oil without absorption competition. Cocoabutter is used little because it exhibits polymorphism, makingtemperature control more important. The fatty acid blends do notexhibit this drawback.
Hydrocortisone USP is a white to practically white, odorless, crystallinepowder that melts at ~215˚C with decomposition. Becausethe fatty acid blend suppository vehicles melt at ~55˚C to 60˚C,hydrocortisone should be thermostabile during the preparationof this formulation. Systemic effects can result from topical application,particularly when applied to broken/bleeding skin. Biologicalhalf-life is ~8 to 12 hours.
USP allows neomycin sulfate, which is the sulfate salt of the"[aminoglycoside] antibacterial substance produced by thegrowth of Streptomyces fradiae Waksman (Fam Streptomycetaceae),or a mixture of 2 or more such salts. It has a potencyequivalent to not less than 600 μg of neomycin per mg, calculatedon the dried basis." (One gram of salt contains not less than600 mg neomycin.) It may be advisable to discuss with the prescriberwhether "neomycin 15 mg" was intended to indicateequivalent potency or quantity of neomycin sulfate. The answermay influence the formulation calculations.
Calculation of density factor when extemporaneously compoundingsuppositories can be a critical issue. In this case, fattyacid blend has density similar to cocoa butter, and available referencesfor displacement factors of ingredients relative to cocoabutter are applicable. If references are not available, severalalternative 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 approximately1.82 g. (Pharmacists always should tare the suppository molds.)This prescription is for 15 mg of neomycin (sulfate) and 50 mg ofhydrocortisone USP per suppository. To provide an elegantpreparation, an additional 1% (~0.018 g) of silica gel can beincluded as a suspending agent. Therefore, this preparation willcontain 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 be1 for calculation purposes. Therefore, each suppository wouldcontain hydrocortisone USP 0.050 g, neomycin sulfate 0.015 g,silica gel 0.018 g, and fatty acid blend 1.74 g. Each item shouldbe increased by 5% to 10% to allow for processing losses.An alternative method, to allow for density factor when formulatingsuppositories, is the "70% Rule." It can be applied where dose isnot critical—eg, where the active ingredient has a wide therapeuticindex or where clinical effect is easily observed. In this case, thedensity factor for a particular ingredient in a particular vehicle isconsidered to be 0.7, and calculations are carried out accordingly.More precise determination of density factor can be obtainedexperimentally by comparing the ratio of average weights ofseveral "blank" suppositories to average weights of several"nonhomogeneous" suppositories compounded by partly fillingeach mold cavity with vehicle, adding a specific, measuredamount of the medicament(s), and then adding sufficient vehicleto fill the cavity.
Mr. Erickson is director of professional affairs at Gallipot Inc.
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