In Vitro and In Vivo Percutaneous Absorption Studies of Ketotifen Patches

Abstract

The purpose of the study is to develop a suitable transdermal delivery system for ketotifen. The physicochemical properties and skin penetration of ketotifen were evaluated for the optimization of the method of patch preparation. The distribution coefficients of ketotifen were determined in octanol/phosphate buffer systems, the partition coefficient and pka value of ketotifen were obtained as 120 and 6.73, respectively. In vitro skin penetration of ketotifen solution was determined at 35°C in the Valia-Chien diffusion cell by using the abdominal skin of nude mouse. The results showed that ketotifen had an optimal skin permeability at pH 7.5. In addition, ketotifen had higher rate of penetration through stripped skin, it was suggested that the main barrier for percutaneous absorption of ketotifen is stratum corneum. Ketotifen patch was fabricated in a stainless mold containing Eudragit S-100 and PEG 400. Other components, tween, span and fatty acids were also incorporated into the patch as penetration enhancers. For animal study, a patch with area of 30 cm² was applied on the dorsal skin of rabbit. The plasma level, after 10 hrs administration were reached 60 ng/mL and maintained a constant level. The results proposed that ketotifen was successfully absorbed through the skin from the applied patch.