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

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.

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Materials

The materials that were used to prepare the pellets, ODTs and to study IND release studies were as follows: In the pellets preparation: The model drug was IND (Tokyo Chemical Industry, Japan), the polymer was Eudragit L100 (Evonik, Germany), plasticizer was sorbitol (Sigma-Aldrich, France), and deionized water was used as a granulation fluid. Rhodamine B (Research Chemicals Ltd., UK) as a colouring agent. In ODTs preparation: Low-substituted Hydroxypropyl Cellulose powder (LHPC) (Shin-Etsu Chemical Co., Ltd., Japan) was used as a binder during powder mixing and disintegrant to prepare ODTs, Stearic acid Magnesium Salt (Sigma-Aldrich, Germany) as a lubricant for tablets compression; Lactose monohydrate (Sigma-Aldrich, Netherlands) as a cushioning agent. The following materials were used for HPLC and in-vitro release studies: Acetic acid glacial (VWR International, France). Acetonitrile (HPLC – SUPER GRADIENT, VWR chemicals, France). Methanol (VWR chemicals, France). Disodium hydrogen phosphate (Alfa Aesar, Great Britain). Sodium hydroxide and sodium chloride (Fischer Scientific, UK). Potassium phosphate monobasic (Honeywell Fluka, Spain).

Al-hashimi, N., Dahmash, E.Z., Khoder, M. et al. Engineering pH-Dependent Orally Disintegrating Tablets for Modified Indomethacin Release: A Polymer-Based Approach. AAPS PharmSciTech 26, 93 (2025). https://doi.org/10.1208/s12249-025-03082-y