Thermodynamic and population balance models for solvent-mediated phase transformation of lansoprazole

Abstract

In this work, two new polymorphs (monohydrate and ethanol solvate) of lansoprazole were first discovered and fully characterized. The transformation between two polymorphs of lansoprazole was investigated both experimentally and theoretically. The ternary phase diagram of the two polymorphic forms of lansoprazole in the binary solvent mixtures of ethanol and water at 15 °C, 25 °C and 35 °C was determined and the thermodynamic model was established. Raman spectroscopy was used to in situ monitor the solvent-mediated transformation from monohydrate to ethanol solvate of lansoprazole, while the solution concentration was measured by UV spectroscopy. The population balance models were established to analyze and compare the dissolution, nucleation and crystal growth process during polymorphic transformation. By combining the experimental and simulation results, the rate-controlling step, the changing profiles of the suspension density and the solid compositions of both polymorphs were investigated and discussed. Furthermore, the effect of temperature on the transformation process was also analyzed.