酮康唑微囊的制备及其药剂学研究

Preparation of ketoconazole microcapsule and its pharmaceutical study

目的 :探讨酮康唑微囊 (Ketoconazolemicrocapsules)的工艺制备条件和质量控制方法 ,研究其成囊后的化学物理稳定性及其体外溶出度 ,为酮康唑微囊新剂型的研制打下基础。方法 :采用复凝聚法、单波长紫外分光光度法、正交法、加速和长期稳定性实验以及转篮法进行酮康唑微囊的制备工艺、定量分析、稳定性及体外溶出度的系列研究。结果 :所得到的微囊平均相对包封率可达 83 4 2 % ,平均粒径为 7 73μm。选定 2 6 9nm为酮康唑的含量测定波长 ,在人工胃液中 ,酮康唑在 0 0 5～ 0 15mg/ml范围内线性关系良好 ,其日间和日内RSD分别为 <0 4 0 %和 2 5 7%。在高温、高湿、强光照及长期室温放置条件下 ,微囊中酮康唑表现出稳定的化学物理性质 ;而在同样条件下 ,酮康唑原料易变色 ,含量变化也很大。酮康唑微囊在人工胃液中 ,90min内可达到最大溶出 ,其最高累积溶出百分率接近 90 0 % ,并且其溶出行为符合Weibull概率函数分布 ,相关参数为 :t1/2 =2 5min ,td=4 2min ,m =0 .6min。结论 :采用复凝聚法制备酮康唑微囊方法简便、易行 ;酮康唑微囊化后 ,可以显著提高其稳定性 ,微囊中酮康唑的质量控制方法简便、可靠 ,并且在人工胃液中有理想的溶出度。

Objective:To explore the preparation technique of ketoconazole microcapsules and the methods of quality control and to study the pharmaceutical characteristics.Methods:The complex coacervation,UV spectrometry,orthogonal design,accelerated and long-term tests and rotating basket method were all employed.Results:The average encapsulating rate of ketoconazole microcapsules was about 83.42%and the mean diameter was 7.73um.The wavelength for ketoconazole content assay was 269nm.In artificial gastric juice,the linear relation was good at the concentration ranging from 0.05mg/ml to 0.15mg/ml and the intraday and interday coefficient RSD were 2.57%and 0.40%,respectively.In the condition of high temperature,high humidity,strong light or long-term room temperature,the ketoconazole in microcapsules showed stable physical and chemical property,on the other hand,ketoconazole powder had a lot of changes in both concentration and color in the same condition.The dissolution of ketoconazole microcapsules in the simulated gastric fluid obeyed the Weibull Distribution. Approximate 90% ketoconazole was released from microcapsules within 90 minutes.The parameters were:t 2/1 =25min,t d=42min,m=0.6min;howerer,the ketoconazole powder released more than 95% ketoconazole within 10 minutes in the same solvent.Conclusion:The preparation of ketoconazole microcapsules is simple and has high loading rate.The way of quantitative assay of ketoconazole microcapsules is reliable and reproducible,the microencapsulation of ketoconazole can improve the stability of ketoconazole and the releasing of ketoconazole from the microcapsules is more sustained than that of ketoconazole powder.