Pharmaceutical cocrystals beyond enteral drug delivery: from concept to translation

Over the past decade, significant research efforts have been dedicated to the development of oral cocrystal dosage forms, giving rise to the launch of groundbreaking medications such as Entresto® and Steglatro®. Numerous scholars have thoroughly examined the rational design and fabrication of pharmaceutical cocrystals, as well as their potential for property enhancement. However, the field pertaining to cocrystal development beyond enteral applications has rarely been comprehensively reviewed, despite such an untapped niche could represent a significant scientific leap to revolutionize the current cocrystal research domain. The stagnation in clinical translation of cocrystal beyond enteral applications, particularly in pulmonary, nasal, and topical delivery, hinders the full realization of its potential for targeted therapy delivery to specific disease sites. Hence, this review aims to explore the feasibility of developing sophisticated non-enteral cocrystal formulations within the confines of our current expertise and understanding. It will begin with an overview of the updated landscape in cocrystal development, followed by a discussion on the importance and merits of redirecting attention towards non-enteral preparation of cocrystals. The critical knowledge gaps that discourage scientists from initiating research in cocrystal beyond enteral use will also be clarified. Finally, future perspectives will be provided to propose innovative approaches to close the knowledge gaps. We believe the insights gained herein offer scientists a guide for formulating non-enteral cocrystal dosage forms in a judicious and effective manner, with the ultimate goal of accelerate the progress of next generation cocrystals for more complicated medical conditions.