The present work deals with the preparation of drug–drug cocrystals of mefenamic acid (MEF) with paracetamol (PAR) using gas antisolvent (GAS) process with an aim to improve the dissolution rate of MEF. Box–Behnken experimental design was used to optimize the GAS process variables for minimal dissolution time of MEF. A mathematical model was developed to study the effects of operating temperature, PAR-to-MEF molar ratio and %MEF saturation in the ranges of 25 °C–45 °C, 3:1–5:1 and 70–90%, respectively. PAR-to-MEF ratio and %MEF saturation were found to be the main parameters affecting the dissolution time. The fastest dissolution time (t_63.2), 11.38 min, was obtained at the optimal conditions of a temperature of 34.9 °C, PAR-to-MEF ratio of 4.3:1 and MEF saturation of 86.8%. Optimized cocrystals by GAS showed that the dissolution rate of MEF improved by 6.0, 5.3 and 2.3-fold when compared to pure MEF, sieved cocrystals prepared by a traditional slow evaporation technique and sieved marketed combination drugs, respectively. GAS cocrystallization thus offers an efficient way to enhance the dissolution rate of the poorly water-soluble drug.

目前的工作涉及使用气体反溶剂（GAS）工艺制备与扑热息痛（PAR）制成的甲芬那酸（MEF）药物-药物共晶体，旨在提高MEF的溶出度。Box–Behnken实验设计用于优化GAS工艺变量，以最大程度地减少MEF的溶解时间。开发了一个数学模型来研究在25°C–45°C，3：1-5：1和70-90％范围内的工作温度，PAR与MEF摩尔比和％MEF饱和度的影响。发现PAR与MEF之比和％MEF饱和度是影响溶解时间的主要参数。最快的溶解时间（t _63.2），在34.9°C的最佳条件下，PAR与MEF的比例为4.3：1，MEF饱和度为86.8％的最佳条件下获得了11.38分钟的时间。通过GAS优化的共晶表明，与纯MEF，通过传统慢速蒸发技术制备的筛分共晶和通过筛分的市售组合药物相比，MEF的溶出速率分别提高了6.0、5.3和2.3倍。因此，GAS共结晶提供了一种提高水溶性差的药物溶解速率的有效方法。