Solubility and apparent thermodynamic analysis of pomalidomide in (acetone plus ethanol/isopropanol) and (ethyl acetate plus ethanol/ isopropanol) and its correlation with thermodynamic model

Co-solvency has been extensively utilized as a very helpful dissolving technique for the poorly soluble pharmaceutical compounds. The dissolution of pomalidomide racemic mixture in four mixtures including (acetone + ethanol), (acetone + isopropanol), (ethyl acetate + ethanol) and (ethyl acetate + isopropanol) over the temperature from 278.15 K to 318.15 K was studied and correlated using the Jouyban-Acree model. In the acetone mixture, the increases occurred monotonously with the increasing mass fraction of acetone, while it increases to a maximum value with the rising concentration of ethyl acetate, and then decreases in ethyl acetate systems. The correlation result was evaluated by relative average deviation (RAD), which indicates that the Jouyban-Acree model can provide a reasonable correlation. The different types of interaction on the solubility were analysed by a multiple linear regression analysis (MLRA). In addition, apparent thermodynamic analysis indicates that the dissolution process of pomalidomide in four mixtures selected is an endothermic and entropy driven process. More importantly, the co-solvency on the dissolution process for pomalidomide is an important aspect of its purification and recrystallization. (C) 2020 Published by Elsevier Ltd.

Automated summary

This study investigated the dissolution of pomalidomide racemic mixture in various solvent mixtures using co-solvency technique and correlated the results using the Jouyban-Acree model. The findings revealed different impact patterns of various solvent mixtures on the solubility of pomalidomide, and the correlation provided a reasonable explanation through multiple linear regression analysis. Additionally, the dissolution process was determined to be endothermic and entropy driven.