Lucio David, Irache Juan Manuel, Font María, Martínez-Ohárriz María Cristina
Department of Chemistry, Faculty of Sciences, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain.
Int J Pharm. 2017 Sep 15;530(1-2):377-386. doi: 10.1016/j.ijpharm.2017.08.002. Epub 2017 Aug 2.
Glibenclamide is an antidiabetic drug showing low bioavailability as consequence of its low solubility. To solve this drawback, the interaction with cyclodextrins has been proposed. The formation of GB-βCDs inclusion complexes was carried out using different methods, βCD derivatives and drug-to-cyclodextrin ratios. The structures of the corresponding complexes have been studied by molecular modelling, X-ray diffraction and differential thermal analysis. The dissolution behavior of inclusion complexes has been compared to that of pure GB. Dimeric inclusion complexes were obtained with different CD disposals, head-to-head for βCD and head-to-tail for HPβCD and RMβCD. Amorphous inclusion complexes were obtained by employing methods of freeze-drying or coevaporation in ammonia-water. However, crystalline structures were formed by kneading and coevaporation in ethanol/water in the case of GB-βCD complexes. The arrangement of these structures depended on the GB:βCD ratio, yielding cage type structures for 1:3 and 1:5 ratios and channel-type structures for higher GB contents. The amount of GB released and its dissolution rate was considerably increased by the use of amorphous inclusion complexes; whereas, slower GB release rates were found from crystalline inclusion complexes formed by kneading or coevaporation in ethanol/water. In addition, it was found that the porous structure strongly conditioned the GB dissolution rate from crystalline products.
格列本脲是一种抗糖尿病药物，由于其低溶解度导致生物利用度较低。为了解决这一缺点，人们提出了其与环糊精的相互作用。使用不同的方法、β - 环糊精衍生物和药物与环糊精的比例来制备格列本脲 - β - 环糊精包合物。通过分子建模、X射线衍射和差示热分析研究了相应复合物的结构。将包合物的溶解行为与纯格列本脲的溶解行为进行了比较。获得了具有不同环糊精排列方式的二聚体包合物，β - 环糊精为头对头排列，羟丙基 - β - 环糊精和随机甲基化β - 环糊精为头对尾排列。通过冷冻干燥或在氨水中共蒸发的方法获得了无定形包合物。然而，在格列本脲 - β - 环糊精复合物的情况下，通过在乙醇/水中捏合和共蒸发形成了晶体结构。这些结构的排列取决于格列本脲与β - 环糊精的比例，对于1:3和1:5的比例产生笼型结构，对于更高的格列本脲含量产生通道型结构。使用无定形包合物可显著提高格列本脲的释放量及其溶解速率；而通过在乙醇/水中捏合或共蒸发形成的晶体包合物的格列本脲释放速率较慢。此外，发现多孔结构强烈影响晶体产物中格列本脲的溶解速率。
