Department of Pharmaceutical Engineering, Wuhan Bioengineering Institute, Yangluo Economic Development Zone, Han-Shi Road 1, Wuhan, China.
Drug Dev Ind Pharm. 2011 May;37(5):606-12. doi: 10.3109/03639045.2010.533277.
The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin-epichlorohydrin polymer (β-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with β-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A(L), which indicated the formation of 1:1 complex between glipizide and β-CDP. β-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-β-CD. The dissolution rate of drug from the β-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/β-CDP systems was higher than that from the corresponding ones with HP-β-CD, which indicated that β-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide /β-CDP inclusion complex after oral administration to beagle dogs.
本研究旨在评估一种新型改性环糊精衍生物——水溶性β-环糊精-表氯醇聚合物（β-CDP）作为一种有效的药物载体，以提高作为难溶性模型药物的格列吡嗪的溶解速率和口服生物利用度。通过共蒸发法制备了格列吡嗪与β-CDP 的包合物，并通过相溶解度、溶解和差示扫描量热法进行了表征。溶解度曲线被分类为 A(L)型，表明格列吡嗪与β-CDP 形成了 1:1 的络合物。与 HP-β-CD 相比，β-CDP 具有更好的提高格列吡嗪水溶解度的性能。药物从β-CDP 配合物中的溶解速率明显大于相应的物理混合物，表明无定形配合物的形成增加了格列吡嗪的溶解度。此外，格列吡嗪/β-CDP 体系中药物溶解速率的增加高于相应的 HP-β-CD 体系，表明β-CDP 可为难溶性药物提供更大的增溶能力。此外，体内研究表明，口服给予比格犬后，格列吡嗪/β-CDP 包合物可显著提高格列吡嗪的生物利用度。
