Determination and Data Correlation of Solubility of Sofosbuvir Polymorphs in Ethyl Acetate + Toluene and Methyl tert-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.

Research on Solubility Measurement, Solvent Effects, Preferential Solvation, and Model Correlation of Sofosbuvir Form A in Different Pure and Binary Solvents

“…Based on the above discussion, these solvents were selected in this work. From investigation, sofosbuvir was found to have limited solubility in water or methyl tert -butyl ether/ethyl acetate + toluene mixtures with limited solvent composition. , The solubility behavior of sofosbuvir is not studied fully. The limited solubility data and lack of high-quality solubility restrict its form screening, production control, and clinical use.…”