Ion pairs of risedronate for transdermal delivery and enhanced permeation rate on hairless mouse skin

Ion-paired solutions of risedronate (RIS) with L-arginine (ARG), L-lysine (LYS), and diethylenetriamine (DETA) were tested in vitro for their potential to enhance the penetration of RIS across the skin of hairless mouse. The xylene solubilities of RIS paired with ARG, LYS, and DETA in molar ratios of 1:2, 1:2, and 1:1 were 8.9%, 12.0%, and 2.1%, respectively, in comparison with the solubility in deionized water, but non-ion-paired RIS was not detected in xylene. In vitro permeation tests were performed on the skin of hairless mice, and the results indicated that ion-paired RIS could penetrate mice skin about 36 times more effectively than RIS alone. The cumulative amount of ion paired RIS after 24h resulted in 475.18 +/- 94.19 mu g/cm(2) and 511.21 +/- 106.52 mu g/cm(2) at molar ratio of 1:2 and 1:1. The cumulative amount of RIS alone was as low as 14.13 +/- 5.49 mu g/cm(2) in 24 h. The hairless mice showed no skin irritation after a single administration of RIS alone and ion-paired RIS (1:2 molar ratio with ARG, and 1:1 molar ratio with DETA). In this study, we found that RIS can be delivered transdermally, and the ion-paired system in an aqueous solution showed an enhanced flux through the skin barrier. (C) 2011 Elsevier B.V. All rights reserved.