盐酸多西环素牙周用微球温敏性凝胶的制剂学研究简

目的构建盐酸多西环素牙周用微球温敏性凝胶缓释系统。方法通过乳化一交联固化法制备盐酸多西环素羧甲基壳聚糖微球（DXY-CMCTS-MS）。采用壳聚糖和卢．甘油磷酸钠（β-GP）制备凝胶。用扫描电镜和光学显微镜观察微球表面形态；体外动态透析法测定释药性能。结果制备的DXY—CMCTS—MS形态圆整，粒径分布较为均匀，平均粒径约25μm，载药量18．9％，包封率64．6％。DXY微球凝胶在室温下为自由流动的液体，37℃的平均凝胶时间为（1．1±0．3）min，明显低于凝胶剂的凝胶时间。微球凝胶复合载体的释药速度明显低于微球剂，体外释药曲线符合Higuchi拟合方程。结论盐酸多西环素微球温敏凝胶复合载体的处方和制备工艺可行，作为牙周用缓释制剂值得进一步研究。

Pharmaceutical Studies on Doxycycline Hydrochloride Microspheres/ Temperature-sensitive Gel Applied to Periodontal Pockets

Objective To develop a doxycycline hydrochloride sustained delivery system for periodontal pockets based on microspheres and temperature-sensitive gel. Methods Carboxymethyl chitosan microspheres loaded with doxyeycline hydrochloride （DXY-CMCTS-MS） were prepared by emulsification cross-linking methods. Chi- tosan/glycerophosphate disodium （glycerophosphate,GP） was used to prepare temperature-sensitive gel. The sur- face morphology of the microspheres was observed under a scanning electron microscope （SEM） and optical micro- scope. The dynamic dialysis method was used to determine the release characteristics of doxycycline hydroehloride in vitro. Results DXY-CMCTS-MS with a sphere shape and narrow distribution was prepared. The average diameter was about 25 μm, the drug loading rate was 18.9% and the encapsulation efficiency was 64.6%. Microspheres/ gel were a freely flowable liquid at room temperature and could form gel in （ 1.1±0.3 ） rain at 37 %, much fsater than hydrogel. Microspheres/gel released drugs much more slowly than microspheres alone. The release profiles con- formed to Higuchi equation. Conclusion This preparation technique is simple and practical, worthy of further studies as sustained preparations for periodontal drug delivery.