Quantification, mechanism, and mitigation of active ingredient phase transformation in tablets.

Model tablet formulations containing thiamine hydrochloride [as a nonstoichiometric hydrate (NSH)] and dicalcium phosphate dihydrate (DCPD) were prepared. In intact tablets, the water released by dehydration of DCPD mediated the transition of NSH to thiamine hydrochloride hemihydrate (HH). The use of an X-ray microdiffractometer with an area detector enabled us to rapidly and simultaneously monitor both the phase transformations. The spatial information, gained by monitoring the tablet from the surface to the core (depth profiling), revealed that both DCPD dehydration and HH formation progressed from the surface to the tablet core as a function of storage time. Film coating of the tablets with ethyl cellulose caused a decrease in both the reaction rates. There was a pronounced lag time, but once initiated, the transformations occurred simultaneously throughout the tablet. Thus the difference in the phase transformation behavior between the uncoated and the coated tablets could not have been discerned with...