Statistical optimization for production of mefenamic acid–nicotinamide cocrystals using gas anti-solvent (GAS) process
Statistical optimization for production of mefenamic acid–nicotinamide cocrystals using gas anti-solvent (GAS) process
复制标题
使用气体反溶剂（GAS）工艺生产甲芬那酸-烟酰胺共晶的统计优化
DOI：
10.1016/j.jiec.2018.01.017
复制
发表时间：
2018
影响因子：
6.1
通讯作者：
Manop Charoenchaitrakool
中科院分区：
文献类型：
--
作者：
Napada Wichianphong;Manop Charoenchaitrakool
本研究旨在利用气体反溶剂（gas）工艺制备MEF - nic共晶，以提高MEF的溶解速率。采用Box-Behnken设计，考察起始溶液中工作温度、共聚物与药物的摩尔比和药物饱和百分比在25-45℃、3-5℃和70-90%范围内的影响。实验设计分析表明，共晶与药物的摩尔比和药物饱和度是影响共晶溶出速度的重要参数。在45℃条件下，共体与药物比为5，药物饱和度为70%是最快溶出时间的最佳条件。此外，在最佳气体蒸发条件下获得的MEF - nic共晶的溶解速度比纯MEF高38倍，比传统慢速蒸发法获得的共晶的溶解速度高1.6倍。
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.