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

Abstract

Although β-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 β-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 λh model, and the ideal model were used to correlate experimentally obtained solubility values. Moreover, thermodynamic analysis of β-lapachone dissolution was performed based on experimental solubility data using the van't Hoff equation. The highest mole fraction solubility of β-lapachone at 298.15 K was found in acetone (2.05 × 10−2), followed by acetonitrile (1.80 × 10−2), ethyl acetate (8.53 × 10−3), 1-butanol (7.43 × 10−3), 1-propanol (6.69 × 10−3), 2-butanol (5.65 × 10−3), methanol (5.40 × 10−3), ethanol (4.99 × 10−3), 2-propanol (3.76 × 10−3), propylene glycol (3.06 × 10−3), and water (2.85 × 10−6). Correlation results showed that the modified Apelblat model was more accurate than the Buchowski-Ksiazaczak λh model and the ideal model. Thermodynamic analysis indicated that β-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 β-lapachone.