Mitigating Drug Stability Challenges Through Cocrystallization

Abstract

Drug stability plays a significant role in the pharmaceutical industry from early-phase drug discovery to product registration as well as the entire life cycle of a product. Various formulation approaches have been employed to overcome drug stability issues. These approaches are sometimes time-consuming which ultimately affect the timeline of the product launch and may further require formulation optimization steps, affecting the overall cost. Pharmaceutical cocrystal is a well-established route to fine tune the biopharmaceutical properties of drugs without covalent modification. This article highlights the role of cocrystallization in mitigating the stability issues of challenging drug molecules. Representative case studies wherein the drug stability issue is addressed through pharmaceutical cocrystals have been discussed briefly and are summarized in tabular form. The emphasis has been made on the structural information of cocrystals and understanding the mechanism that improves the stability of the parent drug through cocrystallization. Besides, a guided strategy has been proposed to modulate the stability of drug molecules through cocrystallization approach. Finally, the stability concern of fixed-dose or drug combinations and the challenges associated with cocrystals are also touched.

Keywords: cocrystal; crystal engineering; degradation pathway; drug stability; structure–property relationship.