硝苯地平生物黏附微球的制备及释药机制研究

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目的:制备硝苯地平生物黏附微球并考察其体外释药情况。方法:在单因素考察的基础上应用正交设计筛选硝苯地平生物黏附微球的最佳处方,因素为加热温度、聚乙烯醇(PVA)用量、司盘浓度和戊二醛用量,评价指标为累积释药率;考察优化处方所制微球的质量指标如体外黏附力和累积释药率等,研究其释药机制。结果:优化处方工艺为:加热温度60℃、PVA用量0.6 g、司盘浓度5%、戊二醛用量0.6 mL;优化处方所制微球体外黏附力较高,平均载药量约为15%,包封率约为85%,平均粒径约为20μm;微球可持续24 h释药,释药符合Higuchi方程,释药机制符合非Fick扩散机制,即以溶蚀和扩散2种模式释放。结论:硝苯地平生物黏附微球制备工艺简单,具有较好的体外黏附性能和缓释效果。 OBJECTIVE: To prepare nisoldipine bioadhesive microspheres and study its in vitro release. Methods: The optimum formulation of screening nifedipine bioadhesive microspheres was established by orthogonal design on the basis of single-factor study. The factors including heating temperature, PVA dosage, Span concentration and glutaraldehyde dosage, For the cumulative release rate; study the optimal formulation of microspheres quality indicators such as in vitro adhesion and cumulative release rate, study its drug release mechanism. Results: The optimized formulation process was as follows: the heating temperature was 60 ℃, the amount of PVA was 0.6 g, the concentration of spondylitis was 5% and the amount of glutaraldehyde was 0.6 mL. The microspheres prepared by optimized formulation had higher in vitro adhesion and the average drug loading was about 15% , The encapsulation efficiency was about 85%, and the average particle size was about 20μm. The microspheres sustained release for 24 h. The drug released conformed to the Higuchi equation. The drug release mechanism was in accordance with the non-Fick diffusion mechanism. Conclusion: The preparation process of nifedipine bioadhesive microspheres is simple, with good in vitro adhesion and sustained release.
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