Al-Hashimi Nihad, Dahmash Eman Zmaily, Khoder Mouhamad, Alany Raid, Elshaer Amr
Department of Pharmacy, School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston Upon Thames, KT1 2EE, UK.
Department of Chemical and Pharmaceutical Sciences, School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston Upon Thames, KT1 2EE, UK.
AAPS PharmSciTech. 2025 Mar 26;26(4):93. doi: 10.1208/s12249-025-03082-y.
The application of pH-sensitive polymers has been widely explored in pharmaceutical industry because of their versatile properties. This work aims to delay the release of indomethacin (IND), a commonly used anti-inflammatory drug, using a pH-dependent polymer within orally disintegrating tablets (ODTs) and to investigate the effect of the polymer particle size on the ODTs. When developing delayed-release formulations for orally disintegrating tablets (ODTs), it's essential to balance the pellet's matrix properties to maintain integrity and delayed release. Different sizes of Eudragit L100 were used to create IND-containing pellets via extrusion spheronization, which were then embedded into the matrix of ODTs. The particle sizes displayed good elastic properties with low Young's modulus (YM) values, and there was no significant difference between the different sizes (45, 60, 93 µm; p > 0.05). The tensile strength of the pellets was directly proportional to YM (p < 0.05), providing enough support to maintain their integrity under compression. Pellets made from 63 µm Eudragit L100 had a suitable balance of mechanical and pharmaceutical properties compared to other sizes. 63 µm pellets had an aspect ratio of 1.49 ± 0.26 and 61% yield, while their ODTs showed a fast disintegration time of 14 ± 0.6 s, while modifying the drug release. Furthermore, IND exhibited modified release in acidic media (pH 1.2) and immediate release in buffer media (pH 6.8). Overall, protecting pellet integrity was crucial to delay release in acidic media and enable immediate release in alkaline media. The newly developed formulation will improve compliance and reduce side effects associated with IND and other irritant drugs particularly in elderly populations.
由于pH敏感聚合物具有多种特性，其在制药行业中的应用已得到广泛探索。本研究旨在利用口服崩解片（ODT）中的pH依赖性聚合物延迟常用抗炎药物吲哚美辛（IND）的释放，并研究聚合物粒径对ODT的影响。在开发口服崩解片的延迟释放制剂时，平衡微丸的基质特性以保持完整性和延迟释放至关重要。使用不同尺寸的Eudragit L100通过挤出滚圆法制备含IND的微丸，然后将其嵌入ODT的基质中。这些粒径显示出良好的弹性性能，杨氏模量（YM）值较低，不同尺寸（45、60、93 µm）之间无显著差异（p > 0.05）。微丸的拉伸强度与YM成正比（p < 0.05），在压缩下能提供足够的支撑以保持其完整性。与其他尺寸相比，由63 µm Eudragit L100制成的微丸在机械性能和药物性能之间具有合适的平衡。63 µm微丸的长宽比为1.49±0.26，收率为61%，而其ODT的崩解时间很快，为14±0.6 s，同时改变了药物释放。此外，IND在酸性介质（pH 1.2）中表现出缓释，在缓冲介质（pH 6.8）中表现出速释。总体而言，保护微丸完整性对于在酸性介质中延迟释放和在碱性介质中实现速释至关重要。新开发的制剂将提高顺应性，并减少与IND和其他刺激性药物相关的副作用，特别是在老年人群中。
