Basic Studies on Controlled Transdermal Delivery on Nicardipine Hydrochloride Using Ethylene-Vinyl Acetate and Ethylene-Vinyl Alcohol Copolymer Membranes

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The permeability of a model drug, nicardipine hydrochloride (NC), through ethylene-vinyl acetate copolymer (EVAc) or ethylene-vinyl alcohol copolymer (EVAl) membrane as a rate controlling layer was examined as one step in the development of a well-designed membrane permeation-controlled transdermal therapeutic system (TTS). The membrane permeability of NC from various suspensions in ethanol (EtOH)-methyl ethyl ketone (MEK)-water mixed solvents was affected by the solvent composition as well as the membrane composition. The NC permeation through EVAc membrane increased with increase in the MEK content in the solvent, whereas that through the EVAl membrane showed a convex curve against MEK content. As solvent penetration into the membranes may be important for the NC permeation, the extent of swelling of EVAc or EVAl beads was determined as an index of solvent pentration. The relationship between the solvent composition and degree of swelling of the copolymer was similar to that between the solvent composition and the logarithm of the product of the steady-state permeation rate of NC through EVAc or EVAl membrane and thickness of the membrane. It was found from the results of the permeation and swelling experiments that the permeability of NC through EVAc or EVAl membrane is mainly affected by the solvent penetration into the membrane. Finally, the effect of EVAll membrane on the permeation of NC through the intact or damaged skin was measured. The NC permation through a piled layer of EVAl membrane and full-thickness skin was similar to that through a piled layer of EVAl membrane and damaged skin. This result suggests that the application of these membranes would be useful in making a well-designed TTS which shows little inter- and/or intra-subject variation in skin permeation of NC.
公益社団法人日本薬学会の論文
1988-07-25

Basic Studies on Controlled Transdermal Delivery on Nicardipine Hydrochloride Using Ethylene-Vinyl Acetate and Ethylene-Vinyl Alcohol Copolymer Membranes

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