ABSTRACT:
Introduction: Aqueous solubility is a critical determinant of the bioavailability and therapeutic efficacy of orally administered drugs, particularly for those classified under BCS Class II and IV. Diclofenac, BCS Class-II drug suffers from poor aqueous solubility, leading to low bioavailability and variable therapeutic outcomes. Objectives: This study explores the use of co-crystallization techniques as an approach to enhance the solubility of diclofenac by using anhydrous caffeine as co-former, also known for its synergistic effects with diclofenac.
Methods: Co-crystals of diclofenac sodium and anhydrous caffeine were prepared using five distinct methods: neat grinding, solvent-assisted grinding, crystallization by melting, solvent evaporation, and anti-solvent approaches. The co-crystals were characterized using infrared spectroscopy, melting point analysis, X-ray diffraction, and DSC. Solubility studies were conducted to evaluate the enhancement in aqueous solubility.
Results: Characterization studies confirmed the successful formation of co-crystals through all five methods. The co-crystals exhibited reduced melting points compared to pure diclofenac sodium, indicating enhanced solubility. IR spectroscopy revealed shifts in characteristic peaks, suggesting the formation of hydrogen bonds and other non-covalent interactions. XRPD analysis confirmed changes in crystallinity, with a trend toward amorphous characteristics. Solubility studies demonstrated a significant increase in the aqueous solubility of diclofenac co-crystals, with the solvent-assisted grinding method yielding the highest solubility of 66mg/ml, compared to 13.62mg/ml for pure diclofenac sodium. Discussion and Conclusion: The solvent-assisted grinding method proved to be the most effective, producing co-crystals with the better solubility. These findings highlight the potential of co-crystallization as a viable approach to address the solubility challenges associated with poorly soluble drugs like diclofenac and offering a promising strategy to improve bioavailability and reduce dosage requirements.
Cite this article:
Vijeth Nagesh Bhat, Rakshitha Munishwarachari, Pallavi Renu Gopal, Sonal Dubey. Co-crystallization of Diclofenac with Caffeine Anhydrous to Enhance Aqueous Solubility. Asian Journal of Pharmaceutical Research. 2026; 16(4):378-4. doi: 10.52711/2231-5691.2026.00055
Cite(Electronic):
Vijeth Nagesh Bhat, Rakshitha Munishwarachari, Pallavi Renu Gopal, Sonal Dubey. Co-crystallization of Diclofenac with Caffeine Anhydrous to Enhance Aqueous Solubility. Asian Journal of Pharmaceutical Research. 2026; 16(4):378-4. doi: 10.52711/2231-5691.2026.00055 Available on: https://www.asianjpr.com/AbstractView.aspx?PID=2026-16-4-2
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