LAUSR

Abstract In recent years, various polymorphic forms have been identified, including solvates of carvedilol. In this study, the solubility values of a thermodynamically stable form (Form I) of carvedilol in acetone, 1-butanol, dichloromethane, ethanol, ethyl acetate, glycerol, methanol, 1-propanol, 2-propanol, propylene glycol, polyethylene glycol (PEG) 400, and tetrahydrofuran were measured at temperatures ranging from 288.15 K to 308.15 K through a solid-liquid equilibrium by using the shake-flask technique. The solubility of carvedilol was lowest in glycerol and greatest in PEG 400, followed by tetrahydrofuran. Based on KAT-LSER model analysis, the sensitivity of the solute-solvent interaction was higher than the solvent-solvent interaction. The specific hydrogen bonding interactions were more important than nonspecific dipolarity/polarizability interactions. The experimentally determined solubility data of carvedilol was well regressed by the modified Apelblat model and the Buchowski-Ksiazczak λh model. The dissolution process of carvedilol was endothermic and spontaneous in the experimental temperature range. Tetrahydrofuran was used as the solvent for the preparation of carvedilol nanoparticles using supercritical antisolvent precipitation. The average particle size of carvedilol nanoparticles (550.8–903.5 nm) was varied using the initial drug concentration in tetrahydrofuran. The solubility data and estimated equations for carvedilol (Form I) in the twelve pure solvents require research and development for the purification and production of micro/nanoparticles.