Solubility of pioglitazone hydrochloride in aqueous solutions of ethanol, propylene glycol, and N-methyl-2-pyrrolidone at 298.2°K

Abstract

Solubility of drugs is a limiting factor to develop liquid drug formulations and also to improve their bioavailability. One of the common methods to increase the aqueous solubility of low soluble drugs is to use the salt forms of drugs. Using hydrochloride form of PGZ, the aqueous solubility is increased from 0.04 (1,3) to 0.7 mM. PGZ-HCl is still a low soluble drug, and additional solubilization method should be employed. In this work, experimental molar solubility and the density of the saturated solutions of PGZ-HCl in aqueous binary mixtures of ethanol, NMP, and propylene glycol at 298.2°K were reported. The solubility of PGZ-HCl was increased with the addition of the cosolvents, and the maximum solubilities are observed at 0.80, 0.90, and 1.00 volume fractions of the cosolvents, respectively. In order to provide a computational method to calculate the solubilities, the Jouyban-Acree model was fitted to the results of these measurements, and solubilities were back-calculated with employing the solubility data in monosolvents in which the overall mean deviation of the models was 11.6%. Two previously trained version of the model were used to predict the solubility of PGZ-HCl in water-cosolvent mixtures employing the experimental solubility data in monosolvents in which the overall prediction error was 57.0%.