Liu Zan, Wang Weiwei, Chen Hao, Liu Jianping, Zhang Wenli
a Department of Pharmaceutics , China Pharmaceutical University , Nanjing , P.R. China.
Pharm Dev Technol. 2016;21(4):405-14. doi: 10.3109/10837450.2015.1016616. Epub 2015 Feb 24.
Actually, reflecting drug release from polymer-coated pellets remains a challenge. In this study, sticking of pellets caused by Eudragit®L30D-55 was observed during the release process, leading to change in drug release. Talcum powder (talc) was used in esomeprazole magnesium pellets to prevent sticking and modify release of pellets. Three methods including talc incorporated in enteric layer, physically mixed and coating resulted pellets were employed to prevent the sticking. The release of pellets was modified by addition talc into subcoat. The dispersion coefficient (Fd) and release profiles were determined in phosphate buffer solution (pH 6.8 and 6.0) and distilled water. It was found that the first manner made Fd increase to about 0.75, but the latter two methods could completely prevent sticking. Also, the second manner was more simple and readily scaled up. In addition, talc in subcoat significantly slowed the drug release in water, but the slowing release effect is less pronounced at pH 6.0 and 6.8. These different effects of talc were attributed to a different release mechanism in three media. The release profiles in water were fitted to Nuttanan model, and the K designated as "diffusive resistance constant" was linearly increased with talc levels in subcoat (R(2)=0.9874).
实际上，反映聚合物包衣微丸的药物释放情况仍然是一个挑战。在本研究中，观察到在释放过程中由尤特奇®L30D - 55引起的微丸粘连，导致药物释放发生变化。在埃索美拉唑镁微丸中使用滑石粉来防止粘连并改变微丸的释放。采用三种方法，包括将滑石粉掺入肠溶层、物理混合以及对制成的微丸进行包衣，以防止粘连。通过在隔离层中添加滑石粉来改变微丸的释放。在磷酸盐缓冲溶液（pH 6.8和6.0）和蒸馏水中测定分散系数（Fd）和释放曲线。发现第一种方法使Fd增加到约0.75，但后两种方法可以完全防止粘连。此外，第二种方法更简单且易于放大生产。另外，隔离层中的滑石粉显著减缓了药物在水中的释放，但在pH 6.0和6.8时缓释效果不太明显。滑石粉的这些不同作用归因于在三种介质中不同的释放机制。水中的释放曲线符合努塔纳模型，被指定为“扩散阻力常数”的K随隔离层中滑石粉含量呈线性增加（R(2)=0.9874）。
