Horiuchi Y, Hirayama F, Uekama K
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Pharm Sci. 1990 Feb;79(2):128-32. doi: 10.1002/jps.2600790211.
Release characteristics of two ethylated beta-cyclodextrins [heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (diethyl-beta-cyclodextrin) and heptakis(2,3,6-tri-O-ethyl)-beta-cyclodextrin (triethyl-beta-cyclodextrin)] as sustained-release drug carriers were evaluated using diltiazem hydrochloride, a water-soluble calcium antagonist. The release rate of diltiazem from compressed tablets was significantly retarded by the complexation with ethylated beta-cyclodextrin. Various environmental effects (such as pH, rotating speed, and additive in the dissolution medium) on the release rate were investigated, together with a microscopic observation of the tablet surface. The water penetration rate into the tablet was measured in order to gain insight into the release mechanism. The results suggested that diltiazem is released slowly from the hydrophobic matrix consisting of diethyl-beta-cyclodextrin following water penetration. When a single dose of tablets containing diethyl-beta-cyclodextrin complex was orally administered to dogs, the sustained-release pattern of the drug, without decrease in area under the plasma concentration-time curve, was produced for a long period. The release rate of diltiazem can be controlled by combining the ethylated beta-cyclodextrin complexes with the parent beta-cyclodextrin complex in different mixing ratios.
以水溶性钙拮抗剂盐酸地尔硫䓬为模型药物，评估了两种乙基化β-环糊精[七（2,6-二-O-乙基）-β-环糊精（二乙基-β-环糊精）和七（2,3,6-三-O-乙基）-β-环糊精（三乙基-β-环糊精）]作为缓释药物载体的释放特性。与乙基化β-环糊精络合后，盐酸地尔硫䓬从压制片中的释放速率显著减慢。研究了各种环境因素（如pH值、转速和溶出介质中的添加剂）对释放速率的影响，并对片剂表面进行了显微镜观察。测量了水进入片剂的渗透率，以深入了解释放机制。结果表明，水渗透后，地尔硫䓬从由二乙基-β-环糊精组成的疏水基质中缓慢释放。当给犬口服单剂量含二乙基-β-环糊精络合物的片剂时，药物的缓释模式得以维持，血浆浓度-时间曲线下面积无下降。通过将乙基化β-环糊精络合物与母体β-环糊精络合物以不同混合比例混合，可以控制地尔硫䓬的释放速率。
