Controlling the chemical stability of a moisture-sensitive drug product through monitoring and identification of coating process microenvironment.

The objective of this work was to monitor and identify the impact of coating microenvironment, as measured by PyroButtons® data loggers, on the chemical stability of a moisture-sensitive drug molecule brivanib alaninate (BA). BA tablets were coated at two different scales (15 and 24in pan). PyroButtons® data loggers were allowed to move freely within the tablet bed to record the temperature and relative humidity conditions of the tablet bed. The tablet moisture content at the end of the coating runs, and the rate of hydrolysis of the BA tablets based on HPLC analysis was found to be a function of the coating thermodynamic microenvironment. Wetter coating conditions resulted in tablets with higher water content and showed greater degradation upon storage. The coating process which yielded acceptable stability in a 15in coater was transferred to a 24in coater by maintaining similar tablet-bed relative humidity and temperature conditions. This was compared to a traditional scale-up approach where the environmental equivalency factor (EEF) was matched between scales during coating. The moisture content observed across the two scales indicated that maintaining a similar tablet-bed microenvironment ensured consistent results between scales.