Solubility, Correlation, Dissolution Thermodynamics and Preferential Solvation of Meloxicam in Aqueous Mixtures of 2-Propanol

Background: Meloxicam is an analgesic drug widely used in current therapeutics. Because the very low equilibrium solubility of meloxicam in neat water, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database of pharmaceuticals in mixed solvents useful for liquid dosage forms design. Methods: Flask shaken method and UV-vis spectrophotometry were used for solubility determinations. Jouyban-Acree model was used for solubility correlation. By using the van’t Hoff and Gibbs equations the respective apparent thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy, were calculated. Further, based on the inverse Kirkwood-Buff integrals the preferential solvation parameters of meloxicam by 2-propanol were calculated. Results: Meloxicam solubility increases with temperature arising and maximum value is observed in the mixture x1 = 0.70 at all temperatures. Jouyban-Acree model correlates the meloxicam solubility very well. Dissolution processes were endothermic in all cases and entropy-driven in the interval 0.20 ≤ x1 ≤ 1.00. Non-linear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 x1 0.40 and variant negative and positive slopes in the other mixtures. Meloxicam is preferentially solvated by water in water-rich mixtures, apparently solvated by water in 2-propanol-rich mixtures, but preferentially solvated by 2-propanol in the interval 0.19 x1 0.78. Conclusion: Solid-liquid equilibrium of meloxicam in {2-propanol + water} mixtures has been studied at several as contribution to preformulation studies of homogeneous liquid pharmaceutical dosage forms.