Study of solubility and thermodynamic properties of amlodipine besylate in binary mixtures of n-methylpyrrolidone, 1-propanol, 2-propanol at different temperatures

Abstract

Introduction: Solubility data has extensive applications in various industries for purpose of dissolution, formulation, and crystallization processes. Various methods exist for altering drug solubility. Cosolvency is recognized as one of the simpler and more effective methods in this field. Objective: The aim of this research is to investigate the solubility and thermodynamic properties of amlodipine besylate in binary mixtures of (N-methylpyrrolidone + 1-propanol), and (N-methylpyrrolidone + 2-propanol) at different temperatures, and to predict solubility data using cosolvency models. Methods: In this study, the shake-flask method was employed for measurement of amlodipine besylate solubility in binary mixtures of solvents. In this process, an excess amount of the drug is added to vessels containing different compositions of solvents. After the solution reaches equilibrium at the specific temperature, the supernatant is separated from the remaining solid material using centrifugation or filtration. Then, after appropriate dilution, UV absorbance of the solution is measured at the drug's maximum wavelength, and the concentration of the samples are determined based on the calibration curve and dilution factors. Then, all acquired data are fitted to mathematical cosolvency models. The thermodynamic properties for dissolution and mixing are calculated using Gibbs and van’t Hoff equations. Results: The obtained data indicates that the solubility of amlodipine besylate increases with an increase in the mass fraction of the cosolvent (N-methylpyrrolidone) and with temperature increase. In both solvent-cosolvent systems, the highest solubility is observed in pure N-methylpyrrolidone at 313.2 K and, the lowest solubility in both systems is observed in pure 1-propanol and 2-propanol, respectively, at 298.2 K. Discussion and Conclusion: The present study demonstrated that with increasing temperature and increasing mass fraction of N-methylpyrrolidone, the dissolution of amlodipine besylate increases significantly. Additionally, the experimental data were compared with calculated data from various cosolvency models, and satisfactory results were obtained modeling accuracy.