Characterization of in Vitro Transdermal Iontophoretic Delivery of Insulin

Abstract

In-vitro studies were conducted to characterize the transdermal iontophoretic delivery of insulin, thus avoiding potential complications from various biological variations, which may be encountered during in-vivo studies. The proteolytic degradation of insulin in skin homogenates and degradation under the experimental conditions used was investigated. Appropriate adjuvants were incorporated to minimize the potential degradation problems of insulin. 125I-Insulin was observed to penetrate into and accumulate in the skin during the iontophoresis period. It was then released gradually from this depot, as a mixture of intact and 125-I labelled fragments, into the receptor medium. Drug desorption studies supported the theory of skin depot or reservoir formation. It was found that an electric field could be used to facilitate the desorption of drug from the depot. The post-application flux of insulin (or its fragments) from the skin depot formed during iontophoresis was monitored to study the factors affecting the iontophoretic delivery of insulin. Stripping and delipidization of the skin were noted to increase the skin permeation rate of insulin. The cumulative radioactivity permeated and accumulated in the skin was higher at pH 3.6 than at pH 7.4. The iontophoresis-facilitated transdermal delivery was observed to increase with increasing duration of current application and increasing donor concentration of insulin. Modulation of drug delivery by multiple applications was also found to be feasible.