ABSTRACT
Solid-state chemical stability of indomethacin powder was tested periodically in drug-adjuvant binary systems stored at different temperatures and relative humidities over a period of 4-12 weeks. Adjuvants studied were those commonly used in filling hard gelatin capsules as well as hydrophilic adjuvants used in solid dispersion techniques. Undegraded indomethacin in the stored samples was determined by spectrophotometry at intervals during storage. Sorbed moisture was periodically assessed gravimetrically. Parachlorobenzoic acid, one of two hydrolytic products, was determined by HPLC at the end of the storage period. Differential thermal analysis of the freshly prepared drug-adjuvant blends was performed. Indomethacin degradation was least in presence of microcrystalline cellulose and high in presence of lactose, polyvinylpyrrolidone, polyethylene glycol and urea. Degradation of indomethacin in presence of these hydrophilic carriers was influenced by the method of sample preparation. Indomethacin degradation in the majority of systems studied reached equilibrium. The extent of drug degradation was linearly dependent on the amount of moisture sorbed. Differential thermal analysis thermograms indicated the interaction between indomethacin and each of polyvinylpyrrolidone, polyethylene glycol and urea