Development, in vitro and in vivo evaluation of film forming solutions for transdermal drug delivery of Zaltoprofen.

Abstract

Zaltoprofen (ZAL) is a non-steroidal anti-inflammatory drug (NSAID) with a short half-life (∼2.8 h) due to extensive first pass metabolism. In this context, 16 different polymeric film forming solutions (PFFS) of ZAL were developed using different grades of Eudragits, Polyvinylpyrrolidones, Kollicoat MAE 100 P and Hydroxypropyl cellulose as film formers, and polyethylene glycol 400 as a plasticizer in equal parts of ethanol and isopropyl alcohol used as solvents. Of these solutions, F13 composed of Kollicoat MAE 100 P emerged as an optimal PFFS as it quickly formed a saturated film (10.25 ± 0.75 min) that displayed low drying time (3.00 ± 0.46 min), and high in vitro adhesion (2.67 ± 0.58). Ex vivo permeation studies conducted in Franz diffusion cell across porcine skin indicated that F13 displayed significantly higher (p < 0.001) steady state flux (8.64 ± 1.72 µg.cm^-2.h^-1), shorter lag time (∼3 h) and better skin content (2.55 ± 0.62 µg/mg) compared to other PFFS. Fourier Transform Infrared Spectroscopy (FT-IR) proved the chemical integrity of ZAL in polymeric film formed from F13, while Differential scanning calorimetry (DSC) and X-ray Diffractometry (XRD) proved the "anti-recrystallization potential" of PFFS. Anti-inflammatory studies in rats indicated that F13 significantly inhibited (ANOVA, p < 0.001) carrageenan induced paw edema for nearly 12 h compared to topical diclofenac used as standard. In addition, significantly elevated (ANOVA, p < 0.001) analgesic effect was noted in the hot plate test in rats treated with F13 compared to the standard for 12 h proving the superior efficacy of F13. Thus, PFFS by virtue of "in situ evaporative metamorphosis" induced supersaturation can be an attractive platform to deliver ZAL transdermally.