Real time monitoring

Solubility is an important parameter with relevance to drug absorption. Poor solubility can result in erraticoral absorption and poor bioavailability. Of further interest, is the susceptibility of compounds to transformfrom one solid form to another with different physical properties. In this study, two different polymorphs of aproprietary Boehringer Ingelheim compound, BIX 011397 (polymorph III) and BIX 011398 (polymorph I)were investigated by the CheqSol (Chasing Equilibrium Solubility, patent applied for) method for equilibriumsolubility measurement.1, 2 The method dissolves and partially reprecipitates ionizable compounds using aGLpKa/D-PAS titration system that can repeatably cycle the solution between a supersaturated andsubsaturated state. Accurate solubility values are determined from the transition between the
supersaturated solution (with solid precipitating) and thesubsaturated system (with solid redissolving). Theobjective was to investigate the feasibility of detecting polymorphic conversions whilst performing theseequilibrium solubility studies. Comparisons were made to traditional shake-flask measurements, and solidswere characterized using TGA, DSC, microscopy and XRPD methods. 解离常数/油水分配系数(pKa/LogP)测定仪