Effect of a wet granulation manufacturing process on the stability of a pharmaceutical drug product

This thesis deals with the application of thermal analysis techniques to understand the root cause of low assay results observed during stability testing of a commercial drug product containing ethinyl estradiol and goes on to suggest improvements that could be made to the commercial manufacturing process to mitigate the stability issues. The potential for formation of different forms of ethinyl estradiol was assessed and subsequent stability of each of the forms established over a range of relative humidities at room temperature.

The anhydrous crystalline and amorphous forms, along with the readily formed chloroform solvate and the less readily formed ethanol solvate of ethinyl estradiol, were subjected to %RH in the range of 11% to 85%. It was demonstrated that the amorphous form and both chloroform and ethanol solvates would revert back to the anhydrous crystalline form within 7 days at ≥54%RH, however, below this %RH there was significant degradation of the active ingredient in the amorphous state, 6.4%-9.5% (n=3) when stored at 33%RH for 87 weeks.