Formulation, Development & Evaluation of Dispersible Tablet of Ethionamide

Abstract

The current study is aimed to develop and evaluate dispersible tablets of Ethionamide, a second line anti-tubercular drug, for increasing patient compliance and therapeutic efficacy in the treatment of multidrug resistant tuberculosis (MDR-TB). However, ethionamide is not well tolerated due to adverse gastrointestinal effects and bioavailability problems. Accordingly, dispersible tablet formulations with different concentration of excipients such as Crospovidone (as superdisintegrant), PVP K-30, Maize starch and Microcrystalline cellulose were formulated by the direct compression method to achieve its quick disintegration and uniform drug dissolution. The prepared batches (F1–F7) were analyzed for weight variation, hardness, friability, thickness, drug content, disintegration time, dissolution test and stability studies. Furthermore, F6 had the best results from all prepared formulae with disintegration time of 45 ± 2 s, friability of only 0.763 ± 0.096% drug content of 99.75 ± 0.74%, and cumulative amount released within first 15 min to be (98.74%). Drug release kinetics was found to fit a Higuchi model (R² = 0.994) and the drug exhibited close to zero-order pattern of release (R² = 0.989), suggesting diffusion-controlled pattern of drug release. Stability studies as per ICH guidelines indicated that the optimized batch lost its physical and chemical integrity under accelerated conditions (40°C/75% RH) for 3 months.The study reveals that the optimized Formulation F6 of Ethionamide dispersible tablet is a fast disintegrating, stable and effective dosage form, which can be a potential way to improve patient compliance, especially in pediatric and geriatric patients who have difficulty in swallowing.

Introduction

The study focuses on developing Fast Dissolving Drug Delivery Systems (FDDS), specifically dispersible tablets of Ethionamide, to improve patient compliance and therapeutic efficacy in tuberculosis (TB) treatment. FDDS are advantageous for patients who have difficulty swallowing, such as pediatric, geriatric, or bedridden populations. TB remains a global health challenge, with treatment hampered by long durations, high pill burden, and poor adherence. Ethionamide, a second-line anti-tubercular drug, suffers from gastrointestinal intolerance and low bioavailability.

Formulation and Preparation:
Ethionamide dispersible tablets were prepared via direct compression, involving four stages: dry mixing, wet granulation with binder solutions, pre-lubrication, and final lubrication. Seven formulations (F1–F7) were designed with varying concentrations of excipients like crospovidone (super disintegrant), MCC (diluent), and sweeteners/flavors to optimize disintegration and patient acceptability.

Evaluation:
All formulations were assessed for physical and mechanical properties including weight variation, thickness, hardness, friability, disintegration time, fineness of dispersion, drug content, in vitro dissolution, and stability.

• Hardness: 3.2–3.5 kg/cm²

• Friability: <1%

• Weight variation: within USP limits

• Drug content: 96.45–99.75%

Key Findings:

• Formulation F6 showed the best overall performance with balanced hardness, minimal friability, uniform weight and thickness, highest drug content (99.75%), and the shortest disintegration time (45 ± 2 sec).

• Rapid disintegration of F6 is attributed to optimized super disintegrant concentration and binder levels, making it the most promising formulation for fast and effective Ethionamide delivery.

Conclusion

The current study confirmed that it could successfully design and evaluate dispersible tablet of Ethionamide to enhance bioavailability and patient compliance. All formulated formulations were found to comply with the pharmacopeial standards in regard to their physicochemical characteristics. Formulation F6 of the seven batches proved to be superior in terms of hardness, friability, drug content, rapid disintegration, and dissolution performance. The optimized formulation demonstrated a minimum disintegration time of 45 s and cumulative drug release of up to 98.74% in 15 min after tracer, based on Higuchi diffusion kinetics with the correlation coefficient R² = 0.994). The stability study demonstrated that F6 was stable at the accelerated and long-term storage conditions. Thus, it may be summarized that ethionamide dispersible tablets; in particular, formulation F6 can be employed as a potential patient friendly alternative to the conventional market preparation of ET, leading faster onset of action and improved compliance for managing MDR TB. This method is capable of minimizing treatment load, which means it might be useful for pediatric, geriatric and dysphagic patients.

References

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Copyright

Copyright © 2025 Atul Bopche, Dhruv Kumar Gupta, Gautam Kumar Verma, Harsh Patel, Harshit Singh, Hemant , Himani Farkare, Dr. Jagdish C. Rathi . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.