Film forming topical dermal spray of meloxicam attenuated pain and inflammation in carrageenan-induced paw oedema in Sprague Dawley rats

Abstract

Meloxicam, a selective COX-2 inhibitor, is well known for ameliorating pain associated with osteoarthritis, rheumatoid arthritis, and mastitis. However, indigestion and stomach upset are most common side effects allied with this drug and raises a concern for its topical delivery Film forming topical dermal spray (FFTDS) was ascertained as the most suitable topical formulation; fabricated for augmenting inflammation and pain. Meloxicam FFTDS was designed with ethanol and DMSO as solvents. Menthol and Eudragit E 100 were used as penetration enhancer and film forming polymer respectively. FFTDS was evaluated for appearance, pH, viscosity, spray pattern, stickiness, water washability, drug assay, and stability. In vivo studies were performed in rats by inducing carrageenan-mediated inflammation and evaluated for COX-2 and caspase-1 expression, pro-inflammatory cytokine levels by Western blot and ELISA. FFTDS exhibited 41.63% paw volume which was insignificantly (P > 0.05) different to the oral dispersion with 33.67% paw volume and significantly (P < 0.05) lower than carrageenan induced paw oedema of 64.68%. ELISA of FFTDS resulted in 4, 2.5 and 1.7 folds decrease in IL-1β, IL-6 and TNF-α levels respectively and significant (P < 0.05) decline in COX-2 and caspase-1 expression as compared to positive control group. Histopathology for paw tissues were also performed. Results revealed marked diminution in inflammation in addition to localization of moderate oedema. Our study thus revealed the potential of FFTDS in alleviating pain and inflammation, showing promising delivery of meloxicam to the site of action via topical route.