Solubility evaluation and thermodynamic modeling of beta-lapachone in water and ten organic solvents at different temperatures

Abstract

Although beta-lapachone is a promising drug with pharmacological activity, issues concerning its low aqueous solubility are known. The objective of this study was to measure the solubility of beta-lapachone in water and ten organic solvents at temperatures ranging from 298.15 K to 318.15 K under atmospheric pressure. The modified Apelblat model, the Buchowski-Ksiazaczak lambda h model, and the ideal model were used to correlate experimentally obtained solubility values. Moreover, thermodynamic analysis of beta-lapachone dissolution was performed based on experimental solubility data using the van't Hoff equation. The highest mole fraction solubility of beta-lapachone at 298.15 K was found in acetone (2.05 x 10(-2)), followed by acetonitrile (1.80 x 10(-2)), ethyl acetate (8.53 x 10(-3)), 1-butanol (7.43 x 10(-3)), 1-propanol (6.69 x 10(-3)), 2-butanol (5.65 x 10(-3)), methanol (5.40 x 10(-3)), ethanol (4.99 x 10(-3)), 2-propanol (3.76 x 10(-3)), propylene glycol (3.06 x 10(-3)), and water (2.85 x 10(-6)). Correlation results showed that the modified Apelblat model was more accurate than the Buchowski-Ksiazaczak lambda h model and the ideal model. Thermodynamic analysis indicated that beta-lapachone dissolution was endothermic and entropy driven process in all solvents studied. Data on solubility and thermodynamic properties in various solvents obtained in this study could be helpful in formulation development, purification, and crystallization of beta-lapachone. (C) 2018 Elsevier B.V. All rights reserved.