Percutaneous absorption enhancer applied to membrane permeation-controlled transdermal delivery of nicardipine hydrochloride.
In the design of nicardipine hydrochloride-transdermal delivery systems (NC-TDS), the enhancing and regulating effects of penetration-enhancers and permeation controlling membranes were evaluated. Laurocapram (Azone) was selected as a model enhancer. Since its enhancing effect is considered to occur in the stratum corneum, its release from ethylene-vinyl acetate copolymers (EVAc), ethylene-vinyl alcohol copolymers (EVAl) or poly(2-hydroxyethylmethacrylate) (pHEMA) membranes was used as a criterion for membrane selection. The release rate was highest from pHEMA. Accordingly, a TDS consisting of a NC reservoir containing 1 w/v% Azone and a pHEMA membrane was prepared, and the effect of skin stripping on the plasma concentration of NC after NC-TDS administration was evaluated in rats. The increased ratio in drug plasma concentration caused by skin stripping was lower when the NC-TDS treatment was compared with a non-regulating NC-gel treatment. Our results suggest that the membrane permeation-controlled TDS of NC may be useful for long-term constant drug delivery with minimum dependence on skin conditions.
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
T
T
Seki
K
K
Sugibayashi
K
K
Juni
Y
Y
Morimoto
D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines; D005079:Excipients; D008297:Male; D008689:Methacrylates; D009529:Nicardipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011145:Polyvinyls; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption / Q000187:drug effects*
D001381:Azepines; D005079:Excipients; D008689:Methacrylates; D011145:Polyvinyls; C035229:laurocapram; C016438:ethylenevinylacetate copolymer; C020320:ethylene-vinyl alcohol copolymer; C005044:hydroxyethyl methacrylate; D009529:Nicardipine