Solubility and thermodynamic properties of hydrate lenalidomide in phosphoric acid solution.

Solubility is important in designing the delivery of the pharmaceuticals and in designing the crystallization process for purification. It is significant to understand the thermodynamics of the stable polymorph and the metastable polymorphs. Lenalidomide can be used for the treatment of multiple myeloma and myelodysplastic syndromes. The lenalidomide solubility of metastable hydrate forms B and E were determined at 0.1 MPa with phosphoric acid solutions in the temperature ranging from 303.15 to 343.15 K. The solubility increased from 8.00 × 10−6 (B) to 9.99 × 10−3 (E) with the rise of temperature and the concentration of phosphoric acid. The solubility has been correlated by the UNIQUAC model, and the molecular interactions between different components in the solution were estimated. To further explain the solubility and understand the molecular interactions in the solutions, the molecular dynamics simulation was used to calculate lattice energy, solvation free energy, and Gibbs energy of solution during the dissolution process. • Phosphoric acid effectively improves the poor solubility of lenalidomide. • Solubility of lenalidomide polymorph was measured in phosphoric acid solution. • Thermodynamic analyses of polymorph were performed based on UNIQUAC model. • Molecular simulation revealed the solubility data of lenalidomide polymorph. [ABSTRACT FROM AUTHOR]