知识与财富的链接
目的:基于有机酸诱导原理制备盐酸普萘洛尔延时脉冲微丸,并研究其体外释药行为。方法:以低渗型丙烯酸树脂为包衣材料,采用空白丸心上药法制备含有机酸的载药微丸,考察处方因素对药物释放的影响,应用Box-Behnken效应面设计优化处方。通过有机酸与包衣膜相互作用试验探索其体外释药机制。结果:药物与琥珀酸分层的微丸具有较理想的脉冲释药特征,最优处方体外释药时滞约为4h,时滞后2h累积释放量90%以上,其体外释放曲线符合logistic模型。有机酸能够降低衣膜的玻璃化转变温度并促进其水化,从而提高包衣膜渗透性而加速释放。结论:所得微丸具有良好的体外脉冲释放效果。
OBJECTIVE To prepare pulsatile release pellets of propranolol hydrochloride with proper lag time based on organic acid induction, and investigate the in vitro drug release. METHODS Pulsatile release pellets were prepared by coating the blank seeds with drug and organic acid, followed by coating with Eudragit®RS. The effect of pellet formulation on in vitro release was evaluated. The formula was then optimized by Box-Behnken design. The release mechanism was explored by investigating the organic acid-film interactions. RESULTS Pellets with drug and succinic acid in separate layers showed ideal pulsatile release characteristics. The optimized pellets showed a lag time of about 4 h and a cumulative release of over 90% at 6 h. Logistic model could be used to fit the release profile. Organic acid increased the permeability of the outer coating and thus the drug release, by promoting film hydration and reducing Tg. CONCLUSION The obtained pellets display good pulsatile release behavior in vitro.
