Department of Chemistry, C.S.G.I, Physical-Chemistry Section, University of Pavia, Via Taramelli 16, 27100 Pavia, Italy.
Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
J Pharm Sci. 2019 Apr;108(4):1529-1539. doi: 10.1016/j.xphs.2018.11.033. Epub 2018 Nov 23.
The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of biopharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. The functional groups involved in the interaction leading to cocrystals formation were investigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug.
本研究旨在合成那格列奈的共晶，那格列奈是生物药剂学分类系统 IIa 类的抗糖尿病药物，作为提高药物溶解度和溶解速率的策略。通过筛选程序，苯甲酰胺被选为合适的共晶形成剂，并制备了不同组成的二元混合物，并通过差示扫描量热法（DSC）进行分析。对 DSC 数据的深入分析可以获得共晶混合物和共晶的组成。强调并解释了这种分析的原理。通过 kneading 和溶剂蒸发制备共晶。通过 DSC 证明了它们的形成，并通过 X 射线粉末衍射、固态核磁共振和傅里叶变换红外光谱得到了确认。通过光谱技术研究了导致共晶形成的相互作用涉及的官能团。体外溶解曲线表明，共晶具有比纯药物更好的药物性能。
