1Department of Pharmaceutics, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Nanded, Maharashtra, India-431715
2S.R. Institute of Pharmacy, Udgir, Maharashtra, India-413517
3Siddharth College of Pharmacy and Research Centre, Boradpada, Badlapur West, Thane, Maharashtra, India-421503
4Sayali Charitable Trust Pharmacy College, Chhatrapati Sambhajinagar, Maharashtra, India-431002
5Dr. Bhanudas Dere Pharmacy College, Sangamner, Maharashtra, India-422611
Correspondence Author:
Shivpuje Shivraj S.
Research Scholar, Department of Pharmaceutics, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Nanded, Maharashtra, India-431715
Email: ssshivpuje147@gmail.com
Poor aqueous solubility continues to hinder the development of many oral drug formulations, restricting both their bioavailability and therapeutic performance. One approach that has attracted increasing attention is co-crystallization, which can alter key physicochemical properties of a compound without changing its pharmacological profile. In this review, we examine how molecular docking and related computational methods can be used to guide the rational choice of co-formers in co-crystal design. Docking studies shed light on binding strength, hydrogen-bond preferences, and other intermolecular interactions, thereby helping to narrow down the pool of potential drug–co-former combinations. We highlight examples involving carboxylic acids, amino acids, and GRAS-listed co-formers, while also pointing out where computational predictions fall short of experimental outcomes, particularly due to limited co-former diversity. Experimental techniques such as PXRD, DSC, and SCXRD are considered alongside current regulatory guidance from the FDA and EMA, since both scientific feasibility and regulatory acceptance are critical to successful development. We conclude by discussing the need to combine docking with molecular dynamics, crystal structure prediction, and machine learning approaches, which together may yield more reliable predictions. Unlike earlier reviews that typically emphasize either computational or experimental perspectives, our aim is to integrate both, and to place them within the broader regulatory context, in order to provide a practical framework for co-former selection.
Keywords: Pharmaceutical co-crystals, molecular docking, co-former selection, drug solubility, computational pharmaceutics, regulatory perspectives.
How to cite this article: Shivpuje SS, Patwekar SL, Pawde PS, Bansode SS, Pohekar AS, Waman RL. Co-Former Selection And Optimization Strategies For Solubility Enhancement Of Drugs: A Review. Int J Drug Deliv Technol. 2026;16(6s): 682-693; DOI: 10.25258/ijddt.16.6s.94
Source of support: None
Conflict of interest: None