Solubility of meloxicam in (Carbitol® + water) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation

Abstract

The equilibrium solubility of meloxicam (3) in {Carbitol® (1) + water (2)} mixtures at several temperatures from 293.15 K to 313.15 K has been determined and correlated by means of some well-known thermodynamic correlation models. Solubility increases 1144 times, from x3 = 1.137 × 10−6 in neat water to x3 = 1.300 × 10−3 in neat Carbitol® at 298.15 K. By using the van't Hoff and Gibbs equations the respective apparent thermodynamic quantities of the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy, were calculated. Apparent dissolution enthalpies vary from a minimum of 7.7 kJ mol−1 in neat water to a maximum of 32.3 kJ mol−1 in the mixture x1 = 0.10. Moreover, apparent dissolution entropies vary from a minimum of −88.0 J mol−1 K−1 in neat water to a maximum of 9.9 J mol−1 K−1 in the mixture x1 = 0.10. Non-linear enthalpy–entropy relationship was observed for meloxicam in the plot of enthalpy vs. Gibbs energy exhibiting negative slope in the composition region 0.00 < x1 < 0.10 and variant but mainly positive slopes in the other mixtures. Hence, the driving mechanism for meloxicam transfer process from more polar to less polar solvent systems is the entropy in water-rich mixtures and the enthalpy in the other solvent compositions. Furthermore, the preferential solvation of meloxicam by Carbitol® and water was analysed by using the inverse Kirkwood-Buff integrals. Meloxicam is preferentially solvated by water molecules in water-rich mixtures exhibiting a maximum in the mixture x1 = 0.10 with δx1,3 = −3.19 × 10−2 but preferentially solvated by Carbitol® molecules in mixtures 0.12 < x1 < 1.00 exhibiting a maximum in the mixture x1 = 0.20 with δx1,3 = 6.87 × 10−2.