Basic studies on controlled transdermal delivery of nicardipine hydrochloride using ethylene-vinyl acetate and ethylene-vinyl alcohol copolymer membranes.

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Abstract
The permeability of a model drug, nicardipine hydrochloride (NC), through ethylene-vinyl acetate copolymer (EVAc) or ethylene-vinyl alcohol copolymer (EVA1) 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 EVA1 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 EVA1 beads was determined as an index of solvent penetration. 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 EVA1 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 EVA1 membrane is mainly affect by the solvent penetration into the membrane. Finally, the effect of EVA1 membrane on the permeation of NC through the intact or damaged skin was measured. The NC permeation through a piled layer of EVA1 membrane and full-thickness skin was similar to that through a piled layer of EVA1 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.