Engineering pH-Dependent Orally Disintegrating Tablets for Modified Indomethacin Release: A Polymer-Based Approach

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Nihad Al-hashimi, Eman Zmaily Dahmash, Mouhamad Khoder, Raid Alany, Amr Elshaer
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Abstract

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.

Graphical Abstract

Graphical illustration for developing delayed release indomethacin loaded Eudragit L100 pellets embedded in orally disintegrating tablets

工程ph依赖性口腔崩解片改良吲哚美辛释放:聚合物为基础的方法
ph敏感聚合物由于其多用途的特性,在制药工业中得到了广泛的应用。本研究旨在通过在口腔崩解片(ODTs)中加入ph依赖性聚合物来延缓消炎药吲哚美辛(IND)的释放,并研究聚合物粒径对其释放的影响。当开发口腔崩解片(ODTs)的缓释制剂时,必须平衡颗粒的基质特性以保持完整性和缓释。采用不同尺寸的Eudragit L100通过挤压球化法制备含铟微球,然后将其嵌入odt基质中。不同粒径(45、60、93µm;p > 0.05)。颗粒的抗拉强度与YM成正比(p < 0.05),在压缩条件下提供足够的支撑以保持颗粒的完整性。与其他尺寸相比,63µm乌龙茶L100制成的颗粒具有合适的机械和药物性能平衡。63µm微丸的长径比为1.49±0.26,得率为61%,odt快速崩解时间为14±0.6 s,并可调节药物释放。此外,IND在酸性介质(pH 1.2)中表现出修饰释放,在缓冲介质(pH 6.8)中表现出立即释放。总的来说,保护颗粒的完整性对于延迟在酸性介质中的释放和在碱性介质中立即释放至关重要。新开发的配方将提高依从性并减少与IND和其他刺激性药物相关的副作用,特别是在老年人中。图示:口腔崩解片缓释吲哚美辛包埋乌龙茶L100微丸的研制
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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