Salicylamide

The poor water solubility of nevirapine (NVP) significantly restricts its bioavailability.To address this challenge, this work proposes an efficient method for screening NVP multicomponent crystals using the full interaction map (FIM) and the Conductor-like screening model for real solvents (COSMO-RS) model.Two NVP salts and two NVP cocrystals with enhanced solubility were prepared using liquid-assisted grinding method and solvent evaporation method, namely nevirapine-5-sulfosalicylate (NVP-5SA), nevirapine-2,6-dihydroxybenzoate (NVP-2,6DBA), nevirapine-2,3-dihydroxybenzoic acid cocrystal (NVP-2,3DBA) and nevirapine-2,5-dihydroxyterephthalic acid cocrystal (NVP-2,5DTA).Systematic characterization, structural anal., solubility measurement, dissolution evaluation and theor. calculations were conducted on these multicomponent crystals.Notably, the solubility of NVP-5SA and NVP-2,6DBA increased to 5.32 and 3.90-fold resp. compared with NVP in phosphate buffer (pH = 6.8).The structures of four multicomponent crystals were characterized using single crystal X-ray diffraction.Quantum chem. calculations, including Hirshfeld surface anal., atoms in mols. theory, independent gradient model based on Hirshfeld partitioning, and mol. electrostatic potentials surface, were employed to study mol. interactions at the microscopic level.The lattice energy (EL) and hydration-free energy (EHF) of NVP and its four multicomponent crystals were calculated, and the relationships between these parameters and the changes of m.p. and dissolution behavior were analyzed.So, the variations and origins of these physicochem. properties were rationalized and explained on the at. scale.Meanwhile, the efficiency of the novel combined coformers screening method was verified.