【摘要】 目的制备乌拉地尔缓释微丸,并初步探讨其释药机制。方法湿法研磨对乌拉地尔进行减小粒径处理,制得粒径d₅₀值约为0.8μm的含药混悬液,结合流化床液相层积法制备载药微丸。以乙基纤维素（EC）和羟丙甲基纤维素邻苯二甲酸酯（HPMCP）为包衣材料制备缓释微丸。以体外释放度为指标筛选处方并与参比制剂进行相似性比较。结合模型拟合分析初步探讨其体外释药性能。结果制得微丸粒度0.67～0.85mm,形状圆整,衣膜光滑,载药量为21.5%,当EC与HPMCP混合质量比为1∶1、包衣增重为5%时在各溶出介质中均与参比制剂的体外溶出情况相似,微丸释放表现为多种因素共同影响的复杂机制。结论成功制备乌拉地尔缓释微丸,工艺简便可行,微丸释放机制以伴随衣膜结构松弛膨胀的扩散为主,并受部分渗透压作用影响。更多还原

【Abstract】 Objective To prepare urapidil sustained-release pellets and to explore its release mechanism. Methods Urapidil was pretreated by wet milling to prepare a drug-containing suspension with the particle size d₅₀ of 0.8 μm and combined with the technology of fluidized bed spray liquid layer deposition to prepare drug-loaded pellets with 21.5% drug loading. The ethyl cellulose（EC） and hydroxypropyl methyl cellulose phthalate（HPMCP） mixed at a certain proportion were used as the coating materials for the preparation of sustained release pellets. In vitro release properties were used as an indicator to select the prescription and compare the similarity with the reference preparation. Model fitting analysis combined with experiments of free membranes were carried out to explore the release mechanism. Results The pellets had a roundness shape and a smooth appearance with a particle size of 0.67–0.85 mm. When the ratio of EC to HPMCP was 1:1 and the coating weight was up to 5%, the dissolution of the pellets was similar to the reference preparations in every dissolution medium. The release of pellets showed a complex mechanism affected by various factors. Conclusion The preparation process is simple and feasible. Drug release from urapdil sustained-release pellets is mainly accompanied by the diffusion and relaxation of the membrane structure, and the contribution of osmotic pressure can be accepted as well.更多还原