Aromatic iminosulfuranes, a novel class of transdermal penetration enhancers

Abstract

In this chapter we introduce iminosulfuranes, a new class of effective chemical penetration enhancers. This group of compounds can be easily synthesized from activated dimethyl sulfoxide (DMSO) and has been found to be chemically stable. Cytotoxicity studies using these iminosulfuranes on human keratinocytes and fibroblasts confirmed their safety at concentrations below 0.2 M. Penetration enhancement effects of several iminosulfuranes on hydrocortisone and caffeine were studied using hairless mouse skin and human skin -(4-bromobenzoyl)--dimethyliminosulfurane was reported as the most potent enhancer among all the tested iminosulfuranes for transdermal delivery of both hydrophobic and hydrophilic drugs. Mechanistic studies suggested that enhancement activity of iminosulfuranes was correlated to their partitioning and residence time in the lipid bilayer system. In addition, -(4-bromobenzoyl)- was rapidly converted to its active metabolite, 4-bromobenzamide, in skin tissues and this biotransformation could further increase hydrocortisone permeation through the skin. Moreover, the elimination of 4-bromobenzamide was inhibited by iodine and alkylating agents.