Superior Dissolution Behavior and Bioavailability of Pharmaceutical Cocrystals and Recent Regulatory Issues
Meng Xia, Bing Q. Zhu, Jian‐Rong Wang, Ze Yang, Xue Mei
Abstract
Cocrystallization has been used extensively to optimize the physicochemical properties of active pharmaceutical ingredients (APIs), such as stability, dissolution, and bioavailability. This review summarizes the history and development of cocrystals, the differences between pharmaceutical cocrystals and salts, and the mechanism underlying the improvement of dissolution through cocrystallization. The correlation of in vitro dissolution and in vivo absorption data (IVIVC) of cocrystals has been discussed as well. Subsequently, guidelines for regulatory classification of cocrystals by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are introduced. Finally, d-α-tocopherol is used as an example to demonstrate the potential of cocrystals in patent generation.