Dissolution Mechanism of Pharmaceuticals and Formulations by Nonequilibrium Thermodynamic Modeling

The dissolution characteristics of active pharmaceutical ingredients (APIs) are extremely critical for their development. This chapter systematically reviews the chemical potential gradient model, perturbed chain statistical associating fluid theory (PC-SAFT), and statistical rate theory used for the analysis and prediction of the dissolution mechanism of API. By reviewing some published work, the chapter addresses the dissolution analysis of pure APIs and API/polymer formulations, as well as the effect of API load, API type, and polymer that have a significant impact on their dissolution, followed by the model prediction of API dissolution. The chemical potential gradient model combined with PC-SAFT has wide application prospects in the analysis of API dissolution mechanism and prediction of dissolution kinetics. Besides, it is helpful to achieve high-throughput screening of formulations by establishing the quantitative relationship between API release rate and intermolecular interaction parameters.