Kaur Karanjit, Kim Kwonho
Drug Delivery Systems Research Laboratory, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439, USA.
Int J Pharm. 2009 Jan 21;366(1-2):140-8. doi: 10.1016/j.ijpharm.2008.09.006. Epub 2008 Sep 13.
Prednisolone (PDS) beads were coated sequentially with (i) innermost hydrophobic layer of Eudragit RS/RL, (ii) middle drug release-triggering layer of chitosan, organic acid and Eudragit RS/RL, and (iii) outermost enteric coating layer. Continuous dissolution studies were carried out in artificial gastric fluid (pH 1.2), followed by intestinal fluid (pH 6.8), and finally in colonic fluid (pH 4 and 6) with and without beta-glucosidase. While drug release was prevented in the gastric and small-intestinal fluids, a continuous release was observed in the colonic fluid. Succinic acid provided the fastest rate of release in the colonic fluid compared to citric, tartaric or malic acid. A combined mechanism of drug release is proposed, which considers the swelling of chitosan and Eudragit RS/RL in the presence of succinic acid possibly via electrostatic interaction between the amine groups of chitosan/quaternary ammonium groups of Eudragit RS/RL and the carboxyl groups of succinic acid in aqueous medium. The results of plasma pharmacokinetic studies in Sprague-Dawley rats showed that the developed system provided a significant delay (T(max) 9.3 h) in the absorption profile of PDS compared with simple enteric-coated (T(max) 4 h) or powder (T(max) 1 h) formulation that was taken as proof for the colon-targeted delivery.
泼尼松龙（PDS）微球依次包被：（i）最内层的乙基纤维素RS/RL疏水层；（ii）中间的壳聚糖、有机酸和乙基纤维素RS/RL药物释放触发层；（iii）最外层的肠溶衣层。在人工胃液（pH 1.2）、随后的肠液（pH 6.8）中，最后在含有和不含有β-葡萄糖苷酶的结肠液（pH 4和6）中进行连续溶出度研究。在胃液和小肠液中药物释放受到抑制，而在结肠液中观察到持续释放。与柠檬酸、酒石酸或苹果酸相比，琥珀酸在结肠液中提供了最快的释放速率。提出了一种药物释放的联合机制，该机制认为壳聚糖和乙基纤维素RS/RL在琥珀酸存在下可能通过壳聚糖的胺基/乙基纤维素RS/RL的季铵基团与琥珀酸的羧基在水性介质中的静电相互作用而膨胀。在Sprague-Dawley大鼠中进行的血浆药代动力学研究结果表明，与简单肠溶包衣（T(max) 4小时）或粉末（T(max) 1小时）制剂相比，所开发的系统使PDS的吸收曲线出现显著延迟（T(max) 9.3小时），这被视为结肠靶向递送的证据。
