Chem. Pharm. Bull. 53(3) 271—276 (2005)

mainly into semisolid formulations such as ointment, cream and lotion and dermal patches such as pressure sensitive adhesive tapes and cataplasma. These topical formulations contain many kinds of pharmaceutical additives. Alcohols, glycols, l-menthol, mineral and vegetable oils and surfactants as well as polymeric additives are prescribed for skin penetration enhancers, drug solubilizers, drug stabilizers, preservatives, excepients, and so on. Polymeric additives sometimes have unique characteristics in the topical formulations. They were used for increase in the compatibility, sustaining of the drug release from the formulations, and stabilization of the active drugs and formulations. Some polymeric additives may be added into a topical formulation for achievement of supersaturate system of drugs. In spite of the increased application of the polymeric additives, their effects and mechanism on the skin permeation of compounds have not been cleared yet. Poly(2-methacryloyloxyethyl phosphorylcholine-co-butylmetacrylate) (PMB) is an amphipathic copolymer of 2methacryloyloxyethyl phosphorylcholine and butylmethacrylate, as shown in Fig. 1. PMB solution seems to be a promising additive of topical formulations, since these polymers were reported to have a preventing effect on the skin roughness and moisturizing action due to their high affinity to the skin surface. In the present study, this unique polymer, PMB, was selected as a candidate polymeric additive for topical formulation. On the other hand, p-hydroxybenzoic acid esters (parabens) have been used broadly as a preservative in many topical formulations. Therefore their low skin permeations are ideal after topical application, whereas their high antibacterial effects are expected in the formulations during the shelf life. p-Hydroxybenzoic acid (p-HBA) and its esters (parabens) were selected as model compounds to evaluate the effect of PMB on their skin permeation because a series of these compounds has similar molecular weight (MW 138— 194) and different n-octanol–water partition coefficients (Kow). Physicochemical parameters of the compounds are shown in Table 1. The present study is aimed at clarifying various effects of PMB on topical formulation from following examinations. Skin permeation of parabens usually correlates with their partition coefficients from the formulation to skin. Then, in vitro skin permeation experiments of parabens were done using different concentrations of PMB, and the effect of PMB on the skin permeation of parabens was evaluated. The site of action of PMB in skin barrier was also estimated by a confocal laser scanning microscopy (CLSM) using fluorescein isothiocyanate (FITC) labeled PBM. Additionally, the effect of PMB on the antibacterial effect of parabens was examined against E. coli and S. aureus. March 2005 Chem. Pharm. Bull. 53(3) 271—276 (2005) 271