Chadha Renu, Rani Dimpy, Goyal Parnika
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
Pharm Res. 2017 Mar;34(3):552-563. doi: 10.1007/s11095-016-2075-1. Epub 2016 Dec 29.
To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties.
Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters.
The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL.
The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.
通过机械化学途径制备格列齐特（GL，一种BCS II类药物分子）的超分子共晶体，以改善其物理化学和生物药剂学性质。
使用液体辅助研磨筛选出两种与具有GRAS状态的共形成物形成的GL共晶体，即癸二酸（GL-SB；1:1）和α-羟基乙酸（GL-HA；1:1）。使用热分析和分析技术对制备的共晶体进行表征，随后评估其抗糖尿病活性和药代动力学参数。
通过DSC和PXRD表征了新的、单一且纯的晶型的生成。由PXRD确定的晶体结构表明两种共晶体均存在于三斜（P-1）晶体系统中。由Material Studio确定的氢键网络得到了FTIR和SSNMR位移的有力支持。与GL相比，这两种新的固体形式均显示出改善的溶解度、IDR、抗糖尿病活性和药代动力学参数。
这些物理化学和生物药剂学性质的改善证实了超分子共结晶在开发具有有趣网络和性质的药物晶体材料方面可能是有用的这一事实。
