Ensslin Simon, Moll Klaus Peter, Haefele-Racin Thomas, Mäder Karsten
Technical Research & Development, Novartis Pharma AG, Basel, Switzerland.
Pharm Res. 2009 Jun;26(6):1534-43. doi: 10.1007/s11095-009-9866-6. Epub 2009 Mar 12.
Aim of the study was to verify the safety of chlorpheniramine maleate pellets, coated with blends of poly(vinyl acetate) and poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer. Therefore, the impact of mechanical forces and storage conditions on the drug release was investigated.
Similar release profiles before and after compression of the pellets to tablets underlined the high film robustness. A damage of the film coat with a razor blade resulted in a premature release, but without a burst. After a similar damage with a needle, the release profile remained almost unchanged, which indicated a swelling based self repair mechanism of the film. Additional studies were dedicated to the storage stability at three different conditions. A slightly delayed release was obtained after 6 months storage at 25 degrees C and a marginally accelerated release was measured after storage at elevated temperatures. No drug migration into the coating layer was detected during storage by confocal Raman microscopy. (1)H-NMR analysis during storage demonstrated, that no polymer or drug degradation had occurred and the plasticizer concentration remained constant.
The polyvinyl based coating blend for modified release pellets demonstrated a high safety, due to their high robustness and compressibility as well as their satisfying storage stability.
本研究旨在验证用聚醋酸乙烯酯和聚乙烯醇-聚乙二醇接枝共聚物混合物包衣的马来酸氯苯那敏微丸的安全性。因此，研究了机械力和储存条件对药物释放的影响。
微丸压制成片剂前后相似的释放曲线突出了包衣膜的高稳定性。用剃须刀片划破包衣膜会导致药物提前释放，但不会出现突释。用针进行类似划破后，释放曲线几乎保持不变，这表明包衣膜存在基于溶胀的自我修复机制。另外还进行了在三种不同条件下的储存稳定性研究。在25℃储存6个月后释放略有延迟，在高温储存后释放略有加速。通过共聚焦拉曼显微镜在储存期间未检测到药物迁移到包衣层中。储存期间的¹H-NMR分析表明，未发生聚合物或药物降解，增塑剂浓度保持恒定。
用于控释微丸的聚乙烯基包衣混合物表现出高安全性，这归因于其高稳定性、可压缩性以及令人满意的储存稳定性。
