Solubility parameter of lenalidomide for predicting the type of solubility profile and application of thermodynamic model

Abstract

The dissolving capacity of lenalidomide in pure and mixed solvents is limited. The purpose of this work is to enhance the solubility and study the solubility parameter of pure and mixtures (δ1) to characterize different types of solubility profiles. The solubility of lenalidomide in acetonitrile (MeCN), methanol (MT), ethanol (EA), ethyl acetate (EAC) and isopropanol (IPA) was experimentally determined at T = 293.15–333.15 K. Its solubility in binary mixtures of EA and EAC was also investigated. The polarity of lenalidomide is related to the tendency of the solubility data against the solubility parameter δ1 of pure and binary solvent mixtures. Consequently, the method of linear solvation energy relationships introduced by Kamlet, Abboud and Taft (KAT-LSER) was applied to analyze the effect of the solute-solvent intermolecular interactions on the solubility in pure solvents. In order to estimate maximum solubility in a specific co-solvent ratio, we also attempt to calculate the Hansen solubility parameter (HSP) of lenalidomide and to compare it with HSP of solvent mixture. Based on the experimental solubility data, two thermodynamic models including modified Apelblat equation and Jouyban-Acree model were then assessed. Meanwhile, a modification of the extended Hildebrand solubility approach (EHSA) including the Hildebrand solubility parameter (δ1) and the acidic and basic partial solubility parameters (δ1a and δ1b) of the solvent mixtures was used to simulate lenalidomide solubility in pure and binary mixture compositions.