Influence of surface acidity of excipients on the solid state stability of pirenzepine

The degradation behaviour of pirenzepine dihydrochloride in the solid state was examined. Buffered granules of various surface acidities were coated with the drug and tested for stability under accelerated conditions at higher temperatures and varying relative humidities. The mixtures were analysed for pirenzepine dihydrochloride and the main degradation product 5, 11-dihydro-6H-pyrido [2, 3b] [1, 4]-benzodiazepine-6-one content using an HPLC assay. Degradation rate constants and reaction parameters were calculated on the basis of an empirical power kinetic function. Rate constants calculated from the Arrhenius plots of the accelerated stability rests showed good correlation with data obtained from long term stability testing. Degradation is influenced by the surface acidity of the buffer granules, resulting in a log k/pHeq profile equivalent to the log k/pH profile in solution. Rate constants were influenced by relative humidity during storage. Relative humidities beyond the critical relative humidity dramatically accelerate decomposition.