Solubility of celecoxib in N-methyl-2-pyrrolidone+water mixtures at various temperatures: Experimental data and thermodynamic analysis

Abstract

Solubility is one of the most significant physicochemical properties of drugs, and improving the solubility of drugs is still a challenging subject in pharmaceutical sciences due to requirements of enhancing their bioavailability. Celecoxib, according to the biopharmaceutics classification system (BCS), is a class 2 drug, possessing low water solubility (<5 μg·mL−1) and high permeability. Increasing the solubility of this group can lead to improved bioavailability, dose reduction and subsequently, increased efficiency and reduced side effects. In this study, celecoxib solubility was determined in binary mixtures of N-methyl-2-pyrrolidone (NMP)+water at 293.2, 298.2, 303.2, 308.2 and 313.2 K. The solubility of celecoxib is increased with the addition of NMP to the aqueous solutions and reaches a maximum value in neat NMP. In addition, increased temperature leads to enhanced solubility of celecoxib in a given solvent composition. The solubility data of celecoxib in NMP+water at different temperatures were correlated using different mathematical models including, the Jouyban-Acree model and a combination of the Jouyban-Acree and van’t Hoff models. Thermodynamic parameters, Gibbs energy, enthalpy and entropy of dissolution processes were performed based on Gibbs and van’t Hoff equations. Thermodynamic analysis allowed observing two main entropy or enthalpy-driven dissolution mechanisms, varying according to the composition of aqueous mixtures. Moreover, preferential solvation of celecoxib by water is observed in water-rich mixtures but preferential solvation by NMP was seen in mixtures with similar composition and also in NMP-rich mixtures.