Preparation of a polymer containing hexadecylpyridinium bromide groups and its utilization as a transdermal drug penetration enhancer

Abstract

A novel polymeric transdermal penetration system was investigated. The polymer was synthesized by the reaction of poly(4-vinylpyridine) and hexadecyl bromide, and its enhancing activity on drug penetration was evaluated by means of in vitro experiments. The amount of 5-fluorouracil (5-FU) that permeated through the skin was determined by using a two-chamber diffusion cell, in which isolated rabbit abdominal skin was mounted. Addition of the polymer effectively enhanced the penetration rate of 5-FU. The permeability coefficient was 2–8 times as much as that in the absence of the polymer. The enhancing activity increased with increase in the degree of quaternization. The mechanism was investigated by differential scanning calorimetry of whole skin and stratum corneum treated with the polymer. Through this investigation, it was shown that, although the polymer interacted with the lipids and proteins of the membranes of the stratum corneum, it may not penetrate into deeper layers of the skin. The absence of irritation of the polymer to the skin was confirmed by the Draize test.