Chlorpropamide의 Cyclodextins와의 Inclusion Complex에 관한 연구

Abstract

經口糖尿病治療樂으로 사용되는 難溶性藥物인 chlorpropamide와 α-cyclodextrin, β-cyclodextrin 및 tri-O-methyl-β-cyclodextrin을 각각 같은 mole比로 凍結乾燥法에 의해 solid complex를 調製하였으며 溶解度 測定, spectroscopy(UV, IR), differential scanning calorimetry 및 粉末 X-ray diffractometry에 의하여 검토한 결과, chlorpropamide가 세종류의 cycledextrin과 1:1의 inclusion complex를 형성함을 확인하였다. 그리고 각 inclusion complex의 溶出特性을 검토한 결과, chlorpropamide의 溶出이 현저하게 증가하였으며, intrinsic dissolution rate는 chlorpropamide에 비하여 chlorpropamide와 α-cyclode-xtrin의 inclusion complex에서 51배 증가하였고 chlorpropamide와 β- cyclodextrin의 inclusion complex는 12배로 증가하였다.;Inclusion complexations of α-cyclodextrin, β-cyclodextrin and tri-O-methyl-β-cyclodextrin with chlorpropamide in aqueous solution and in the solid state were studied by the solubility method, spectroscopy (UV, IR), differential scanning calorimetry and powder X-ray diffractometry, and all their molar ratios were found to be 1:1. The solid complexes of chlorpropamide with three kinds of cyclodextrins were prepared by a freeze-drying method, and their dissolution behaviors were examined. As a result, the release of chlorpropamide from the inclusion complexes was significantly improved. The intrinsic dissolution rate of chlorpropamide in cyclodextrin inclusion complexe was about 51 times ( α-cyclodextrin inclusion complex) and 12 times ( β-cyclodextrin inclusion complex) larger than that of intact chlorpropamide.