Effect of permeation enhancers on the release and permeation kinetics of meloxicam gel formulations through rat skin

Purpose: The main aim of this research was to study the effect of various penetration enhancers on the permeation of meloxicam gel through skin in order to avoid oral delivery side effects such as irritation of the gastrointestinal tract, and systemic toxicity and to achieve a better therapeutic effect. The influence of various penetration enhancers, such as isopropyl myristate, dimethyl sulfoxide, and various fatty acids from different subclasses like mono-unsaturated (oleic acid), and poly-unsaturated (linoleic acid), on the percutaneous absorption of meloxicam from Carbopol gels containing 40% propylene glycol was investigated. Methods: Skin permeation experiments were carried out using excised abdominal rat skin. The in vitro transdermal penetration of these formulations was evaluated using a Franz diffusion cell. Furthermore, a pharmacodynamic study of meloxicam was carried out to evaluate its anti-inflammatory activity on a carrageenan-induced rat paw edema model and a skin irritation study was also carried out on rabbits. Results: Oleic acid was found to be the most efficient enhancer for meloxicam, followed by linoleic acid. With 5% oleic acid, meloxicam gel showed a permeation rate of 33.06±0.81 µg·cm-2·h-1, which was 7-fold higher compared with control gel. In the paw edema test, 5% oleic acid and 5% linoleic acid were the most effective. Conclusion: The in vitro and in vivo studies showed that use of penetration enhancer allows local delivery of meloxicam at the inflammation site and also its systematic absorption.

Keywords: Meloxicam Penetration enhancers Gel formulations Oleic acid Linoleic acid Albino rats