RELATIONSHIP BETWEEN POLYMORPHISM AND SOLUTION STRUCTURE OF A DRUG SUBSTANCE, BONE PROTON POMP INHIBITOR (BPPI)

摘要

A drug substance, bone proton pomp inhibitor (BPPI), has two crystal polymorphs (B01-form and B02-form). The B02-form appeared from a BPPI-methanol solution, while the B01-form appeared from an ethanol solution. We attempted to make a relation between the precipitation of polymorphs and the structure of solution. The structure of BPPI molecules and intermolecular interaction in the solution were analyzed by nuclear magnetic resonance spectroscopy (NMR). The results indicated that the structure of BPPI molecular aggregates in a methanol solution was different from that in an ethanol solution. It was suggested that the aggregate structure in a methanol solution is advantageous to the precipitation of the B02-form.