Nechipadappu Sunil Kumar, Tekuri Venkatadri, Trivedi Darshak R
Department of Chemistry, Supramolecular Chemistry Laboratory, National Institute of Technology, Karnataka (NITK), Srinivas Nagar, Surathkal, Mangaluru, Karnataka 575025, India.
Department of Chemistry, Supramolecular Chemistry Laboratory, National Institute of Technology, Karnataka (NITK), Srinivas Nagar, Surathkal, Mangaluru, Karnataka 575025, India.
J Pharm Sci. 2017 May;106(5):1384-1390. doi: 10.1016/j.xphs.2017.01.033. Epub 2017 Feb 7.
Two novel pharmaceutical co-crystals of anti-inflammatory drug flufenamic acid (FFA) with 2-chloro-4-nitrobenzoic acid (CNB) and ethenzamide (ETZ) have been synthesized by solvent evaporation method as well as by solvent drop-assisted grinding method. The synthesized co-crystals were characterized thoroughly by various spectroscopic methods and crystal structures were determined by single-crystal x-ray diffraction technique. In FFA-CNB co-crystal, robust supramolecular acid-acid homosynthon was observed. FFA-ETZ co-crystal is formed via robust supramolecular acid-amide heterosynthon. In FTIR spectra, a significant shift in the carbonyl stretching frequency was observed for the co-crystals due to the presence of intermolecular hydrogen bond. H nuclear magnetic resonance study suggests the presence of hydrogen bond in the solution state of FFA-ETZ co-crystal; however, it was absent for FFA-CNB co-crystal. Solubility study in Millipore water revealed that the solubility of FFA is increased by 2-fold when it is in the form of FFA-CNB co-crystal and no increment in the solubility of FFA was observed in FFA-ETZ co-crystal. About 5-fold increment in the solubility of FFA was observed in both the co-crystals in 0.1 N HCl (pH 1) solution. The synthesized co-crystals were found to be non-hygroscopic at ∼75% relative humidity and stable for a period of 6 months at ambient temperature (∼25°C).
通过溶剂蒸发法以及溶剂滴加辅助研磨法合成了抗炎药物氟芬那酸（FFA）与2-氯-4-硝基苯甲酸（CNB）和乙磺酰胺（ETZ）的两种新型药物共晶体。通过各种光谱方法对合成的共晶体进行了全面表征，并通过单晶X射线衍射技术确定了晶体结构。在FFA-CNB共晶体中，观察到了强大的超分子酸酸同合成子。FFA-ETZ共晶体是通过强大的超分子酸-酰胺异合成子形成的。在傅里叶变换红外光谱中，由于分子间氢键的存在，共晶体的羰基伸缩频率发生了显著位移。氢核磁共振研究表明，FFA-ETZ共晶体在溶液状态下存在氢键；然而，FFA-CNB共晶体中不存在氢键。在微孔水中的溶解度研究表明，FFA以FFA-CNB共晶体形式存在时，其溶解度增加了2倍，而在FFA-ETZ共晶体中未观察到FFA溶解度的增加。在0.1 N HCl（pH 1）溶液中，两种共晶体中FFA的溶解度均增加了约5倍。发现合成的共晶体在相对湿度约75%时不吸湿，在室温（约25°C）下可稳定6个月。
