Piper Betle: A Promising Tool for Drug Permeation Enhancement of Naproxen Sodium Transdermal Gel Formulation

The main objective of present investigation was to study the influence of Piper betle on the permeation of Naproxen sodium gel when applied on skin. This route avoids the side effects of NSAIDS on oral administration like irritation of the gastrointestinal tract, and systemic toxicity and improves the patient compliance and therapeutic efficacy. The leaves of P. betle were subjected to maceration using successive solvent extraction with solvents like n-hexane, chloroform, methanol and water. All four extracts were screened for preliminary phytochemical tests. The carbopol gel formulations containing Naproxen sodium (1% w/w) and selected concentrations (1% / 2% w/w) of synthetic penetrations enhancers or four herbal extracts were prepared as various batches. These formulations were subjected to characterization tests of colour, pH, viscosity, spreadability. Formulations were subjected to ex-vivo permeation of the drug across rat skin using Franz diffusion cell. The permeation using herbal extracts was compared with synthetic penetration enhancer, Transcutol P(TP). The formulation containing 2% w/w of N- hexane extract (NHE) showed better % cumulative release (47.97%) and flux (157.072 µg/cm2.h), as compared to synthetic enhancer transcutol P (43.11% CR and flux as 141.15 µg/cm2..h) and other extracts. Histopathology shows focal stripping of stratum corneum and normal adnexal structure in both these formulations (containing NHE & TP). But mild degeneration of epidermis and dermis was seen along with hemorrhage in skin treated with formulation containing TP. The results suggest that Piper betle may be safer and better option for increasing the skin permeability of Naproxen sodium as compared to synthetic penetration enhancers.