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 wer e coated with the drug and tested for stability under accelerated cond itions at higher temperatures and varying relative humidities. The mix tures were analysed for pirenzepine dihydrochloride and the main degra dation product 5, 11-dihydro-6H-pyrido [2, 3b] [1, 4]-benzodiazepine-6 -one content using an HPLC assay. Degradation rate constants and react ion parameters were calculated on the basis of an empirical power kine tic function. Rate constants calculated from the Arrhenius plots of th e accelerated stability rests showed good correlation with data obtain ed from long term stability testing. Degradation is influenced by the surface acidity of the buffer granules, resulting in a log k/pHeq prof ile equivalent to the log k/pH profile in solution. Rate constants wer e influenced by relative humidity during storage. Relative humidities beyond the critical relative humidity dramatically accelerate decompos ition.