Formulation And Evaluation of Mefenamic Acid Cocrystals for Taste Masking and Solubility Enhancement

Background: Mefenamic acid (MA), a BCS Class II drug, exhibits poor aqueous solubility and an intensely bitter taste, which limit its oral bioavailability and patient compliance, especially among pediatric and geriatric populations. To address these challenges, the present study focused on the formulation and evaluation of cocrystals of mefenamic acid with selected coformers citric acid, sucralose, saccharin, mannitol, and aspartame. Objective: To enhance the solubility and mask the bitterness of mefenamic acid through cocrystallization with coformers. Methods: Cocrystals were prepared in a 1:1 molar ratio, among that MA: Mannitol and MA: Aspartame shows significant enhancement in solubility but aspartame is sweeter than mannitol therefore it was screened for further study. The prepared cocrystals were characterized using FTIR, DSC and PXRD. In vitro dissolution studies were conducted and taste masking was evaluated using a human sensory panel. Results: All cocrystals showed evidence of hydrogen bonding in FTIR and distinct new endothermic peaks in DSC thermograms, confirming cocrystal formation. PXRD patterns exhibited new diffraction peaks and suppression of original peaks, indicating the formation of new crystalline phases. Among all coformers, the MA: Aspartame (1:2) cocrystal exhibited the most favorable profile, achieving 90.72% drug release in 60 minutes compared to 49.04% for pure MA. Taste evaluation results showed complete elimination of bitterness in the MA: Aspartame cocrystal versus high bitterness for the pure drug. Although MA: Mannitol showed slightly higher solubility enhancement, although aspartame’s stronger sweetness provided significantly better taste masking. Statistical analysis confirmed the difference was highly significant (p < 0.001). Conclusion: The cocrystallization of mefenamic acid with aspartame (1:2) successfully improved both solubility and palatability, making it the most effective formulation among the tested coformers. This approach holds promise for developing patient-compliant oral dosage forms of poorly soluble and bitter-tasting drugs.