Enhanced skin permeation of small molecules via retention of enhancer substances in matrix-type transdermal patches

Abstract

A long-standing approach to improve the transdermal drug permeation is to use chemical penetration enhancers. Those substances reduce the barrier properties of the skin, especially of the stratum corneum, and facilitate the transdermal permeation of drug substances. The incorporation of enhancer substances in transdermal patches would be highly desirable; however, due to the volatility of certain compounds this is extremely challenging.<br /> This work is focussed on the feasibility of transdermal systems containing volatile penetration enhancers (dimethyl sulfoxide and Transcutol^®). Different drug substances (Estradiol, Ibuprofen, Scopolamine, and Rotigotine) were used as model compounds to evaluate the release from the prepared systems and the transdermal permeation. Enhancers and drug substances were incorporated in matrix-type patches where the excipients are embedded in a self-adhesive matrix. The prepared patches contained various enhancer concentrations due to different drying temperatures and times that allowed a complete polymer solvents removal while retaining significant amounts of enhancer. The resulting patches were analysed for enhancer content, drug and enhancer release, drug and enhancer permeation through excised porcine skin, stability, and physicochemical properties.<br /> The skin permeation for Estradiol and Scopolamine was significantly increased by dimethyl sulfoxide (DMSO), Transcutol^® improved the permeation of Estradiol as well. The effects of the enhancer substances on the permeation behaviour of the different drugs were examined. The investigation revealed that the interaction between drug, enhancer and matrix polymer had a crucial influence on drug release and on drug permeation. For instance, the presence of DMSO had no influence on the release and permeation of Ibuprofen and Rotigotine but improved the drug delivery of the other drugs. Regarding stability, the presence of enhancer substance had the beneficial effect of inhibiting the drug recrystallization at even lowest concentrations. Storage stability was limited to six months and stabilizing attempts with silica particles did not improve the stability.<br /> Although the technical feasibility range is relatively narrow, such enhancer-containing matrixtype patches are able to significantly enhance drug permeation through the skin while ameliorating the product stability against recrystallization.