Determination and Data Correlation of Solubility of Sofosbuvir Polymorphs in Ethyl Acetate + Toluene and Methyl <i>tert</i>-Butyl Ether Binary Solvents at the Temperature Range from 268.15 to 308.15 K

Abstract

A gravimetric method was used to experimentally determine the (solid + liquid) equilibrium of sofosbuvir of crystalline forms A and B in both ethyl acetate + toluene and methyl tert-butyl ether (MTBE) + toluene binary solvents systems at atmosphere pressure. Experiments were carried out at a temperature range of 268.15−308.15 K. Results show that the solubility of sofosbuvir increases with temperature, and the solubility of form B was higher than that of form A. The modified Apelblat model, the CNIBS/Redlich−Kister model, and the combined version of Jouyban−Acree model were employed to correlate the measured solubility data, respectively. Furthermore, an examination of the solid-state stability of the two polymorphs was conducted, finding that form A and form B exhibit good solid-state stability under high temperature, high humidity, and strong light exposure conditions.

Keywords

• sofosbuvir
• polymorph
• solubility
• binary solvents
• data correlation