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The purpose is to assess physical and chemical degradation of select pharmaceutical formulations from the Shuttle and ISS medical kits. Eleven pharmaceuticals dispensed as different dosage forms were selected based on their physical / chemical characteristics and susceptibility to environmental factors such as, temperature, humidity and light sensitivity. When available, ground-controls of the study medications with matching brand and lot numbers were used for comparison. Samples retrieved from flight were stored along with their matching controls in a temperature and humidity controlled environmental chamber. Temperature, humidity, and radiation data from the Shuttle and ISS were retrieved from onboard HOBO U12 Temp/RH Data Loggers, and from passive dosimeters. Physical and chemical analyses of the pharmaceuticals were conducted using validated United States Pharmacopeia (USP) methods. Results indicated degradation of 6 of the 11 formulations returned from space flights. Four formulations, Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, and ciprofloxacin tablets depicted discoloration after flight. Chemical content analyses using High or Ultra Performance Liquid Chromatography (HPLC / UPLC) methods revealed that dosage forms of Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, lidocaine, ciprofloxacin and mupirocin contained less than 95% of manufacturer s labeled claim of active drug compound. Shuttle and ISS environments affect stability and shelf life of certain mediations flown on these missions. Data analysis is in progress to examine the effect of specific space flight environmental factors on pharmaceutical stability. The degradation profiles generated from ground studies in analog environments will be useful in establishing predictive shelf-life profiles for medications intended for use during long-term space exploration missions.

The current vision for manned space flight involves lunar and Martian exploration within the next two decades. In order for NASA to achieve these goals, a significant amount of preparation is necessary to assure crew health and safety. A mission critical component of this vision centers around the stability of pharmaceutical preparations contained in the space medicine kits. Evidence suggests that even brief periods of space flight have significant detrimental effects for some pharmaceutical formulations. The effects observed include decreases in physical stability of drug formulations of sufficient magnitude to effect bioavailability. Other formulations exhibit decreases in chemical stability resulting in a loss of potency. Physical or-chemical instability of pharmaceutical formulations i n space medicine kits could render the products ineffective. Of additional concern is the potential for formation of toxic degradation products as a result of the observed product instability. This proposal addresses Question number 11 of Clinical Capabilities in the Critical Path Roadmap. In addition, this proposal will reduce the risks and/or enhance the capabilities of humans exposed to the environments of space flight or an extraterrestrial destination by identifying drugs that may be unstable during spaceflight.