Solubility Prediction and Dissolution Mechanism Analysis of Etodolac in Complex Polymer Solutions Based on Thermodynamic and Interfacial Mass Transfer Models

In this work, the solubilities and dissolution profiles of etodolac were determined in water with four polymers (PEG 6000, PEG 20000, PVP K25, and HPMC E3) at 300.15 305.15, 310.15, 315.15, and 320.15 K. The results show that all four polymers used in this work have solubilization effects on etodolac, and the solubilities of etodolac in medium increase with the increase in the temperature and polymer mass fraction in medium. From the point of view of the solubilization effect on etodolac, HPMC E3, PEG 6000, PVP K25, and PEG 20000 are in order from the best to the worst. A two-step chemical potential gradient model combined with PC-SAFT (Perturbed-Chain Statistical Associating Fluid Theory) and interfacial mass transfer model was used to model the dissolution profiles of etodolac. The results show that the dissolution mechanism of etodolac is affected by the temperature, stirring speed, type of polymer, and mass fraction of polymer in medium so as to regulate the dissolution rate of etodolac, which is expected to provide theoretical guidance for the screening of pharmaceutical excipients. Based upon the determined rate constants, the predicted dissolution profiles of the tablets under different conditions were in good accordance with the experimental data.