Vemula Sateesh Kumar, Narala Sagar, Uttreja Prateek, Narala Nagarjuna, Daravath Bhaskar, Kalla Chamundeswara Srinivasa Akash, Baisa Srikanth, Munnangi Siva Ram, Chella Naveen, Repka Michael A
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.
Pharmaceutics. 2024 Sep 27;16(10):1265. doi: 10.3390/pharmaceutics16101265.
A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work.
The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon.
Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit S 100 coating, and 93.96% in extended release up to 24 h in the colonic region.
Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.
采用制粒机结合热熔挤出技术（HME）来制备酮洛芬（KTP）的结肠靶向微丸。酮洛芬的热稳定性以及在上消化道的副作用使其更适合此项研究。
在羟丙甲纤维素HME 4M存在的情况下，使用酶触发聚合物果胶低甲氧基（Pectin LM）制备微丸，随后进行pH依赖型聚丙烯酸树脂S 100包衣，通过减少药物在上消化道（GIT）的释放，使药物在结肠实现最大程度的释放。采用Box-Behnken设计（BBD）对不同自变量（如Pectin LM（A）、羟丙甲纤维素HME 4M（B）和聚丙烯酸树脂S 100（C））的比例进行响应面优化，以降低药物在上消化道的早期释放并延长其在结肠的释放。
固态表征研究表明，酮洛芬以固溶体状态存在于热熔挤出的聚合物基质中。通过考虑设计空间获得的制备优化后的KTP微丸的预期响应显示，在2小时内药物释放率为1.20%，借助聚丙烯酸树脂S 100包衣，在滞后阶段的前5小时内释放率为3.73%，在结肠区域长达24小时的缓释过程中释放率为93.96%。
因此，开发聚丙烯酸树脂包衣的热熔挤出微丸可能是实现酮洛芬结肠特异性释放的一种重要方法。
