This research aimed to enhance the dissolution rate of mefenamic acid (MEF) by preparing a novel cocrystal containing MEF, paracetamol (PAR) and nicotinamide (NIC) via the Gas Anti-Solvent (GAS) process. Box−Behnken design of experiments was implemented to evaluate impacts of various process variables on the dissolution rate of MEF and find optimal conditions for the production ternary system cocrystal with the highest dissolution rate of MEF. The results showed that the fastest dissolution time (t_63.2) of 4.19 min was obtained when using the precipitation temperature of 25 °C, NIC−PAR−MEF molar ratio of 4.78:4.78:1 and % MEF saturation of 89.74 %. The obtained cocrystals from GAS at the optimal conditions exhibited an improved dissolution rate 16.40 times higher than that of unprocessed MEF. In order to obtain a product containing a ratio of MEF to PAR that is in line with commercially available drugs (MEF to PAR mass ratios are in the range of 0.4–1.54) and exhibiting a high dissolution rate of MEF, further experiments were conducted using different ratios of PAR to NIC. It was found that the GAS products prepared at 25 °C with the use of % saturation of MEF at 89.74 % and NIC−PAR−MEF molar ratio of 12:2.39:1 (OPT1) had t_63.2 value of 2.88 min and MEF to PAR mass ratio of 0.65. When using the NIC−PAR−MEF molar ratio of 9.56:1:1 (OPT2), the product had t_63.2 value of 3.30 min and MEF to PAR mass ratio of 1.52.

本研究旨在通过气体反溶剂 (GAS) 工艺制备含有 MEF、扑热息痛 (PAR) 和烟酰胺 (NIC) 的新型共晶，以提高甲芬那酸 (MEF) 的溶出速率。实施 Box-Behnken 实验设计，以评估各种工艺变量对 MEF 溶解速率的影响，并找到生产具有最高 MEF 溶解速率的三元体系共晶的最佳条件。结果表明，最快的溶解时间（t _63.2) 在使用 25 °C 的沉淀温度、4.78:4.78:1 的 NIC-PAR-MEF 摩尔比和 89.74% 的 MEF 饱和度时获得 4.19 分钟。在最佳条件下从 GAS 获得的共晶表现出比未加工的 MEF 提高 16.40 倍的溶解速率。为了获得与市售药物一致的 MEF 与 PAR 比例（MEF 与 PAR 质量比在 0.4-1.54 范围内）并表现出 MEF 高溶出度的产品，进一步实验使用PAR 与 NIC 的不同比率。发现在 25°C 下使用 89.74% 的 MEF 饱和度和 12:2.39:1 (OPT1) 的 NIC-PAR-MEF 摩尔比制备的 GAS 产品的 t 为_63.2值为 2.88 分钟，MEF 与 PAR 质量比为 0.65。当使用 NIC-PAR-MEF 摩尔比为 9.56:1:1 (OPT2) 时，产物的 t _63.2值为 3.30 分钟，MEF 与 PAR 的质量比为 1.52。