Sterile Topical Dosage Forms I: Laboratory Phase

Abstract

A laboratory investigation was conducted to evaluate the use of conventional sterilizing techniques to manufacture sterile topical dosage forms. Four types of topical dosage forms were investigated: (a) an ophthalmic ointment, (b) a topical cream, (c) a topical ointment, and (d) a topical lotion. Dry-heat sterilization was found to be an acceptable method to sterilize the ophthalmic ointment vehicle. Moist-heat sterilization was found to be an acceptable method to sterilize the topical cream vehicle, part of the topical ointment vehicle, and also part of the topical lotion vehicle. Membrane filtration sterilization was found to be an acceptable method to sterilize the active ingredients in the topical cream, part of the topical ointment vehicle, and the active ingredients and part of the topical lotion vehicle. Ethylene oxide gas sterilization was found to be an acceptable method to sterilize an insoluble, inactive ingredient and the ointment tubes for all four types of topical dosage forms. Residual ethylene oxide determinations showed that longer “venting” times were required for phenolic and urea-formaldehyde capped tubes than polyethylene capped tubes. A microorganism suspension, consisting of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Aspergillus niger, and Candida albicans, was used in the contamination studies. In all cases, the sterilized contaminated samples passed the sterility test. A variety of analytical techniques was employed to verify that the sterilizing procedures did not degrade the sterilized material. Included in these techniques were GC, color, and rheology. Aseptic processing of the sterilized components, under conventional sterile room conditions and under laminar air flow, did not present any major problems. All samples passed the finished-product sterility test. All sterile products passed the nonsterile finished-product specifications and showed equivalent chemical and physical stability.