阿苯达唑固体分散体及其肝动脉栓塞分散微球的研究

目的以具有优良成型性的壳聚糖（CS）为载体，选用阿苯达唑（ABZ）为模型药物，先制备成固体分散体，再进一步制备阿苯达唑壳聚糖微球（ABZ-LSD-CS），考察微球载药量、包封率、表面形态及理化特性，并考察微球在不同介质中的体外释放特性。方法以液体石蜡为油相，Span-80为乳化剂，戊二醛为交联剂，采用乳化-交联固化法制备ABZ-LSD-CS。应用扫描电镜（SEM）观察微球的表面形态，光学显微镜测量粒径大小及分布；采用红外光谱（FT-IR），X-射线粉末衍射（XRD）法和差示扫描量热（DSC）法表征微球特性，体外动态透析法测定微球在不同介质条件下的释药性能。结果制备出的微球形态圆整，粒径分布较均匀，平均粒径为（153±7）μm，载药量（20．92±0．15）％，包封率（25．37±0．22）％。微球在0．1mol／LHCl、pH3．5和7．4的PBS及生理盐水4种介质中的释放缓慢，其中在pH3．5的PBS中释放效果最好，符合Weibull释放模型。结论该实验制备的ABZ．CS-MS性能良好，具有较好的药物载药量和包封率，微球形态圆整，并且药物的释放时间延长，达到缓释的目的，制备工艺简单易行。

Studies on preparation of albendazole and its chitosan microspheres for hepatic artery embolization

Objective This article chooses chistosan with excellent formability as a carrier, alben- dazole as model drug to study the preparation technique of albendazole solid dispersions. And albendazole- loaded chitosan microspheres （ABZ-LSD-CS） were futher prepared. The encapsulation efficiency, drug- loading amount, average diameter, superficial shape, and physical and chemical properties were also in- vestigated. Methods Albendazole-loaded chitosan microspheres for embolization were achieved by emul- sification cross-linking process with liquid paraffin as oil phase, Span-80 as emulsifier, and glutaralde- hyde as cross linking agent. The surface characterization of the microspheres was identified with scanning electronic microscope （SEM）, and the particle size and distribution of microspheres were analyzed by op- tical microscope. （FT-IR） and XRD and DSC were used to characterize microspheres. In vitro dynamic dialysis method was used to determine the drug release property of microspheres in different media condi- tions. Results A novel microspheres with a global shape and narrow distribution were prepared. The av-erage diameter was about （ 153±7 ）μm, drug-loading amount was （20.92±0.15 ） %, and encapsulation efficiency was （25.37±0.22 ） %. The drug release behavior in 0.1 mol/L HC1, phosphate buffered sa- line （ pH = 3.5 ）, phosphate buffered saline （ pH = 7.4） and physiological saline was slow. The release in pH = 3.5 was best of all, which conformed to weibull distribution model. Conclusion The prepared ABZ-LSD-CS have a good property of high drug loading amount and entrapment efficiency, whose surfaces were smooth and round. The in vitro release time of drug was increased obviously, so that sustained drug re- lease was achieved. The preparation technique is very feasible.