POLYMERIZATION OF BENZALKONIUM CHLORIDE-TYPE MONOMER AND APPLICATION TO PERCUTANEOUS DRUG ABSORPTION ENHANCER

A novel type of polymeric transdermal penetration enhancer, which itself permeated through the skin only with difficulty, was synthesized, and its enhancing activity was ascertained by means of in vitroexperiments. Its enhancing mechanism was also investigated by DSC measurement. The polymeric enhancer was prepared by radical polymerization of a cationic surfactant monomer, p-vinylbenzyldimethylalkylammonium chloride containing a long alkyl group. The enhancing activity was evaluated by measurement of the amount of 5-fluorouracil (5-FU) permeated through the skin, using a two-chamber diffusion cell having an isolated rabbit abdominal skin mounted between half cells. Among the monomers having different alkyl groups, that possessing a hexadecyl group showed the most effective enhancement of permeation of 5-FU through the skin. Further, addition of the resulting polymers effectively enhanced the permeation of 5-FU. The extent of enhancing activity increased with decreasing molecular weight of the polymer. From the DSC results, it was evident that both the monomeric and the polymeric enhancer interacted with the lipid and protein portion in the stratum corneum; however, the polymer scarcely penetrated any deeper than the stratum corneum. It was discovered from these results that the enhancing activity of the polymeric material was closely related to the molecular weight, and that the polymerization of the penetration enhancer prevented irritation to the skin. © 1990.