Experimental measurement, thermodynamic analysis and molecular simulation of topiramate solubility in fourteen mono-solvents at various temperatures

A novel antiepileptic drug of topiramate (TPM) has remarkably boosted the human health to against epilepsy. Herein, the solubility of TPM was measured in fourteen mono-solvents through a method of laser monitoring at temperatures from 278.15 to 323.15 K in this work. Moreover, the electrostatic potential surfaces and quantum chemistry calculation at molecular level were applied to explain the solubility differences. The multiple factors such as the polarity of solvent, active sites interaction, the molecular size and free volume all affect the solubility of TPM. Not only the solubility data of TPM were obtained, but also the thermodynamic properties of TPM in various solvents were studied. The solid–liquid phase equilibrium solubility of TPM was regressed and corrected by five thermodynamic models including λ-h, NRTL, NRTL-SAC, UNIQUAC models and modified Apelblat equation, and the classical van't Hoff equation was employed to analyze the thermodynamic properties during the process of TPM dissolution. This research will provide basic data for the production of TPM in the pharmaceutical industry.