Effect of skin permeation enhancers on transdermal delivery of zaltoprofen from polymeric film forming solutions

Polymeric film-forming solutions (PFS) of Kollicoat MAE 100 P were developed using the high-speed dispersion technique for transdermal delivery of Zaltoprofen (ZAL). Azone, oleic acid-propylene glycol, d-Limonene, and 1,8-cineole were explored as skin permeation enhancers in PFS F1, F2, F3 and F4, respectively. The PFS F3, was found to display a significantly shorter (p < 0.05) drying time (4.04 ± 0.48 min) and crystallizing time (12.10 ± 0.90 min) compared to other PFS. The characteristic Infra Red peaks of ZAL were clearly evident in the spectra of the PFS, confirming chemical integrity of ZAL in PFS. X-ray Diffractometry (XRD) and Differential Scanning Calorimetry (DSC) of the films formed collectively indicated that ZAL was dispersed in an amorphous state in the polymeric matrix. In vitro permeation of PFS conducted in a Franz diffusion cell indicated that the PFS F3 and F4 significantly enhanced (p < 0.0001) the flux of ZAL by ∼3 and ∼1.92 folds, respectively, compared to enhancer-free PFS across porcine skin. Pharmacokinetic studies in rats indicated that PFS F3 significantly increased (p < 0.001) the Cmax and Area Under the Curve by ∼2.32 and ∼2.31 folds, respectively, compared to ZAL transdermal patch. Further, pharmacodynamic studies in rats indicated that PFS F3, significantly reduced (p < 0.001) the pain compared to normal control for 24h, thereby displaying extended analgesic effect. Histological evidence proved the safety of F3 as it did not induce any structural changes in the epidermis as well as the dermis. The studies proved that PFS composed of d-Limonene as SPE can safely deliver ZAL transdermally.