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ORIGINAL RESEARCH ARTICLE

Characterization and in vitro stability of tolfenamic acid-loaded carboxymethylcellulose ethanolic hydrogels

Syeda Ayesha Ahmed un Nabi1 ,  Muhammad Ali Sheraz1 ,  Sofia Ahmed1 ,  Sadia Hafeez Kazi1 ,  Raahim Ali1 ,  Safoora Tariq1 ,  Zubair Anwar2* ,  Arif Sabah3
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1 Department of Pharmaceutics, Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Sindh, Pakistan
2 Department of Pharmaceutical Chemistry, Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Sindh, Pakistan
3 Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi, Sindh, Pakistan
INNOSC Theranostics and Pharmacological Sciences, 025170027 https://doi.org/10.36922/ITPS025170027
Received: 21 April 2025 | Revised: 14 January 2026 | Accepted: 23 January 2026 | Published online: 15 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Tolfenamic acid (TA) is a fenamate nonsteroidal anti-inflammatory drug with expanding therapeutic potential, but its clinical use is limited by systemic side effects and the lack of topical formulations. Developing a stable topical gel may enable localized delivery of TA while minimizing systemic exposure. In the present study, simple hydroalcoholic gel formulations of TA with carboxymethylcellulose sodium (CMC) were prepared, with or without propylene glycol (PG), at pH 6.5. Before the formulation step, the interactions and compatibility of the TA/CMC (1:1) physical mixtures were studied using Fourier transform infrared spectroscopy and high-performance liquid chromatography. The formulated gels were stored at room temperature (27 ± 2°C) for six months and evaluated for their physical and chemical stability. The results indicated that gels prepared without PG showed greater moisture evaporation, resulting in higher viscosity, spreadability, and swelling index, with lower weight loss. No syneresis was observed in either gel formulation under different conditions, except under acidic conditions, where syneresis was observed. Microscopic evaluation of the formulations revealed polymorphic changes of the drug in the gels during storage. Both gels demonstrated optimal chemical stability, with negligible degradation throughout the study. Release kinetic studies indicated that TA followed the Higuchi model, with almost 100% drug release within 2.5 h.

Keywords
Tolfenamic acid
Gel formulation
Humectant
Stability
Interaction
Release kinetics
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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