目的 制备帕罗西汀树脂复合物, 并对其结构、体外药物释放和掩味效果进行评价。方法 以药物利用率、载药量和反应速率常数作为响应因子, 利用完全析因设计筛选树脂复合物制备的工艺和处方参数(如反应温度, 搅拌速度, 溶液药物浓度, 树脂与药物质量比)。通过扫描电镜、差示扫描热分析、药物体外释放和掩味效果评价来表征和评价药物树脂复合物。结果 影响帕罗西汀树脂复合物制备的最重要因素是树脂药物比和反应温度, 且其在酸性或盐溶液条件下能完全释放(>96%)并具有良好的掩味效果。同时表征结果显示药物树脂复合物的构成机制主要是离子交换而非物理吸附。结论 通过处方、工艺优化可制备出性能良好的帕罗西汀树脂复合物, 并促进帕罗西汀混悬仿制制剂的开发。
Abstract
OBJECTIVE To prepare and characterize paroxetine resinate, and evaluate the in vitro drug release rate and taste-masking effect. METHODS A full factorial design was first conceived and applied to screen some process and formulation parameters (reaction temperature, stirring speed, drug concentration in solution and the ratio of resin to drug) on the key responses of resinationprocess, such as drug utilization ratio, drug loading and complexation constant. The paroxetine resinate was then characterized and evaluated by scanning electronic microscope (SEM), differential scanning calorimetry (DSC), in vitro drug release test and panel test of taste-masking. RESULTS The resin/drug ratio and reaction temperature were identified as the most important factors on paroxetine resinate preparation.The drug-resin complex was successfully formed via ion exchange mechanism rather than physical absorption with complete in vitro drug release (>96%) in acidic or salt solution and good taste-masking effect.CONCLUSION Paroxetine resinate with good performance can be prepared via optimization of process and formulation parameters, which will facilitate the development of generic paroxetine suspension.
关键词
离子交换树脂 /
帕罗西汀树脂复合物 /
完全析因设计 /
掩味效果
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Key words
ion exchange resin /
paroxetine resinate /
full factorial design /
taste-masking
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中图分类号：
R944
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