Zubair Anwar

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.