Solubility, solution thermodynamics and molecular interactions of osimertinib in some pharmaceutically useful solvents

A key factor in dosage form development is selection of a suitable solvent for the solubility of drugs. Solubility data of osimertinib (OSM) are scarce in the research literature. In current study, thermodynamic solubility of OSM in eight different pharmaceutically useful solvents namely, water, ethanol, propylene glycol (PG), ethyl acetate (EA), isopropyl myristate (IPM), dichloromethane (DCM), Transcutol-HP (THP), and polyethylene glycol-400 (PEG-400) at the temperature from (298.2 to 318.2) K under air pressure of 0.1 MP were determined. The solid state characterization confirmed no transformation of OSM into polymorphs. The mole-fraction solubility of OSM was obtained greatest in PEG-400 (7.33 x 10(-3)) and least in water (3.69 x 10(-5)) at 318.2 K. The solubility data of OSM was regressed by "Apelblat and van't Hoff models" with overall deviations of 1.64 and 2.37%, respectively. Ideal solubility was calculated much higher than experimental solubilities of OSM at different temperatures. The activity coefficients were calculated with the help of ideal solubilities, and found highest molecular interaction between OSM and PEG-400. Thermodynamic parameters confirmed endothermic and entropy driven dissolution in all investigated solvents. (C) 2019 Elsevier B.V. All rights reserved.