Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

Background

Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats.

Results

FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation.

Conclusion

Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs.