Statistical optimization for production of mefenamic acid–nicotinamide cocrystals using gas anti-solvent (GAS) process

Abstract This study aims to produce mefenamic acid–nicotinamide (MEF–NIC) cocrystal using gas anti-solvent (GAS) process in order to improve dissolution rate of MEF. Box–Behnken design was used to investigate the effects of three operating parameters: operating temperature, coformer-to-drug molar ratio and %drug saturation in the starting solution in the ranges of 25–45 °C, 3–5 and 70–90%, respectively. The analysis of experimental design showed that coformer-to-drug molar ratio and %drug saturation are significant parameters affecting the dissolution rate of the cocrystals. At a temperature of 45 °C, a coformer-to-drug ratio of 5 and a %drug saturation of 70% were found to be the optimal conditions for achieving the fastest dissolution time. Additionally, the sieved MEF–NIC cocrystal obtained from the optimal GAS conditions showed an enhanced dissolution rate 38 times greater than that of pure MEF and 1.6 times greater than cocrystal from a traditional slow evaporation method.