Design, characterization, and evaluation of an aceclofenac cocrystal for improved solubility and stability

Background: Co-crystallization enhances APIs by forming noncovalent interactions with coformers, thereby improving physicochemical properties. Aceclofenac was selected for its low solubility, whereas L-lysine serves as a coformer to enhance solubility and stability via hydrogen bonding. This strategy effectively improves the solubility, stability, and bioavailability of poorly soluble drugs. Methods: The aceclofenac–lysine co-crystal was synthesized using the Neat Grinding technique. The synthesized cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Hot stage microscopy (HSM), and Fourier transform infrared spectroscopy (FTIR). Dissolution behavior, stability, and in vivo anti-inflammatory activity were evaluated in comparison with pure aceclofenac. Results: PXRD and DSC confirmed a new crystalline phase, while FTIR revealed hydrogen bonding between aceclofenac and lysine. The cocrystal exhibited a 2.66-fold improvement in dissolution (91.84% vs. 34.41% at 90 min) and superior stability, maintaining >86% dissolution after six months at 40°C/75% RH, compared to ~30% for pure aceclofenac. In vivo studies demonstrated enhanced anti-inflammatory efficacy, with 81.50% edema inhibition versus 74.35% with the pure drug (p < 0.0001). Discussion: The ACF-lysine cocrystal achieved dissolution enhancement that maintained stability over six months, and demonstrated statistically significant improvement in anti-inflammatory efficacy, confirming superior therapeutic performance over pure aceclofenac. Conclusion: Co-crystallization with L-lysine effectively enhanced aceclofenac's biopharmaceutical and pharmacological performance. The aceclofenac-lysine co-crystal exhibited 2.66-fold faster dissolution, greater stability under accelerated storage, and significantly improved anti-inflammatory efficacy (81.50% vs. 74.35% edema inhibition; p < 0.0001) compared with pure aceclofenac. These results demonstrate the value of amino acid coformers in improving the solubility of poorly soluble drugs.