Lappaconitine solid dispersion monolithic osmotic tablet and lappaconitine push-pull osmotic pump: preparation and comparison of their release performance in vitro  

高乌甲素固体分散体单层渗透泵和高乌甲素双层渗透泵的制备及体外释药行为研究(英文)

作　　者：吴先闯[1] 王姣姣[2] 郝海军[2] 宋晓勇[1] 张永州[1] 刘瑜新[1] 张红芹 

机构地区：[1]河南大学淮河医院药学部,河南开封475000 [2]上海医药工业研究院,上海201203 [3]上海艾韦特医药科技有限公司,上海201203

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第6期413-422,共10页中国药学（英文版）

基　　金：Science and Technology Department of Henan Pro vince Fund Project(Grant No.144300510019)

摘　　要：Lappaconitine is a water-insoluble drug, which was used as model drug in this study. Currently, two osmotically controlled delivery systems that are widely used for water-insoluble drug are monolithic osmotic tablet （MOT） and push-pull osmotic pump （PPOP）. In the present study, lappaconitine solid dispersion monolithic osmotic tablet （lappaconitine-SD-MOT） and lappaconitine-PPOP were developed. The prepared lappaconitine-PPOP was able to delivery drug at the rate of approximate zero-order （r = 0.9931）, and the cumulative release was above 95.0%. The lappaconitine-SD-MOT showed a comparatively poor linearity when the data were plotted according to the zero-order equation （r = 0.9798）, and the cumulative release was 84.69%. Lappaconitine-PPOP exhibited better controlled drug release （higher regression value） compared with lappaconitine-SD-MOT. The similarity index （f2） between lappaconitine-PPOP and lappaconitine-SD-MOT was 49.1 （〈50）. A clear difference of drug release characteristics between the lappaconitine-SD-MOT and lappaconitine-PPOP was revealed. It indicated that the drug release performance of lappaconitine-PPOP could gain favorable zero-order kinetics and higher cumulative release compared with lappaconitine-SD-MOT. Therefore, these results suggested that PPOP was still a very effective device for the delivery of poorly water-soluble drug with zero-order pattern.高乌甲素水溶性较差,作为本研究模型药,对难溶性药物来说,目前主要采用单层渗透泵和双层渗透泵两种控释技术来制备渗透控释制剂。本研究分别制备了高乌甲素固体分散体单层渗透泵和高乌甲素双层渗透泵。高乌甲素双层渗透泵控释片可以近似零级释药速率进行释药(r=0.9931),累积释放度达到95.0%。而高乌甲素固体分散体单层渗透泵控释片与高乌甲素双层渗透泵相比(r=0.9931)零级释药特征相对较差(r=0.9798),累积释放度为84.69%。因此,高乌甲素双层渗透泵与高乌甲素固体分散体单层渗透泵相比,在控制药物释放方面更具优势(更高的零级释放拟合度)。高乌甲素双层渗透泵和高乌甲素固体分散体单层渗透泵相似因子f_2为49.1(<50.0),两种渗透泵控释制剂体外释放特征明显不同。高乌甲素双层渗透泵零级释药效果优于高乌甲素固体分散体单层渗透泵,且累积释放度也较高。因此,双层渗透泵技术在控制难溶性药物释放方面比单层渗透泵更具优势,但制备过程较为复杂。

关 键 词：LAPPACONITINE Solid dispersion Monolithic osmotic tablet Push-pull osmotic pumps 

分 类 号：R943[医药卫生—药剂学]