Bruni Giovanna, Berbenni Vittorio, Maggi Lauretta, Mustarelli Piercarlo, Friuli Valeria, Ferrara Chiara, Pardi Francesca, Castagna Federica, Girella Alessandro, Milanese Chiara, Marini Amedeo
a C.S.G.I. - Department of Chemistry, Physical-Chemistry Section , University of Pavia , Pavia , Italy.
b Department of Drug Sciences , University of Pavia , Pavia , Italy.
Drug Dev Ind Pharm. 2018 Feb;44(2):243-250. doi: 10.1080/03639045.2017.1386208. Epub 2017 Oct 17.
To improve the pharmaceutical behavior of the oral antidiabetic agent gliclazide through the synthesis of multicomponent crystals with tromethamine.
Multicomponent crystals were prepared by solvent evaporation method, kneading, and combining mechanical and thermal activation. DSC, FT-IR spectroscopy, X-ray diffraction, SEM-EDS, and SSNMR were used to investigate their formation. Measurements of solubility and dissolution rate were carried out for the pharmaceutical characterization.
The formation of multicomponent crystals of gliclazide and tromethamine was confirmed by all the techniques. In particular, FT-IR and NMR measurements revealed that the interaction between drug and coformer leads to significant changes of the hydrogen bond scheme, and that almost all the functional groups of the two molecules are involved. The dissolution profile of the new phase is significantly better than that of both pure gliclazide and of the reference commercial product Diabrezide.
The new system shows an improved pharmaceutical behavior and could be formulated in a dosage form to obtain a rapid and complete release of the drug available for absorption.
通过与 tromethamine 合成多组分晶体来改善口服抗糖尿病药物格列齐特的药学行为。
采用溶剂蒸发法、捏合以及机械和热活化相结合的方法制备多组分晶体。利用差示扫描量热法（DSC）、傅里叶变换红外光谱法（FT-IR）、X 射线衍射法、扫描电子显微镜-能谱分析法（SEM-EDS）和固体核磁共振法（SSNMR）研究其形成过程。进行溶解度和溶出速率测定以进行药物表征。
所有技术均证实了格列齐特与 tromethamine 多组分晶体的形成。特别是，FT-IR 和核磁共振测量表明药物与共形成剂之间的相互作用导致氢键模式发生显著变化，且两个分子的几乎所有官能团都参与其中。新相的溶出曲线明显优于纯格列齐特和参比市售产品 Diabrezide。
新体系显示出改善的药学行为，可制成剂型以实现药物的快速完全释放从而可供吸收。
