COCRYSTAL FORMATION OF PARACETAMOL WITH INDOMETHACIN AND MEFENAMIC ACID: AN EFFICIENT APPROACH TO ENHANCE SOLUBILITY

Objective: Drug molecules with limited aqueous solubility are rather challenging in formulation development and may pose the risk of insufficient exposure and thus poor efficacy in patients upon oral administration. Co-crystallization is the process to enhance the physical properties of the molecule, especially the solubility. Mefenamic acid and indomethacin belong to nonsteroidal anti-inflammatory agents (NSAIDs) and are often combined with paracetamol in various formulations. Co-crystallization technique was used to combine two drugs in a single solid phase and thus to achieve a newer approach for combination therapy. Using the newer approach co-crystals of mefenamic acid and indomethacin with paracetamol were prepared. Method: Co-crystallization of two drugs was carried out in different solvent systems using different methods like solvent evaporation, grinding, antisolvent addition and ultrasound assisted techniques. COOH---N and COOH---O heterosynthons were used as an element in the co-crystal design strategy. Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD) techniques were employed to support the formation of cocrystals and to find out the optimized ratio of components of co-crystals. Results and Conclusion: Synthesis of co-crystals of mefenamic acid and indomethacin with paracetamol was successfully carried out by different methods from which solvent evaporation method was found to be the best amongst all methods for the selected APIs. Ethanol proved to be the best solvent for the formation of co-crystals among the selected solvent system. The results from DSC and X-ray Powder Diffraction analysis revealed the formation of co-crystals of indomethacin and mefenamic acid with paracetamol.