IN-VITRO IN-VIVO DIFFERENCE IN ENHANCED SKIN PERMEATION OF NICARDIPINE HYDROCHLORIDE BY THE 1-MENTHOL-ETHANOL SYSTEM

The in vitro/in vivo difference in enhanced skin permeation of nicardi pine hydrochloride (NC) by simultaneous use of I-menthol and ethanol(M EW system, 1-menthol:ethanol:water = 5:40:55) was investigated in hair less rats. First, the cutaneous blood flow clearance (clearance from s kin to blood flow) of NC per unit area of skin (CL(CB)/A), which was c omparable to the permeability coefficient across skin (P-C), was calcu lated from intracutaneous and intravenous injection data using the dec onvolution method; the value was 1.67 mu l/h/cm(2). Two formulations c ontaining hTC and the MEW system, solution (SOL) and 15% hydroxypropyl cellulose gel (GEL), were used for in vitro and in vivo permeation ex periments. The in vitro P-C of NC via excised skin from SOL (23.3 mu l /h/cm(2)) was significantly higher than CL(CB)/A, and that from GEL (1 .48 mu l/h/cm(2)) was similar to CL(CB)/A. Consequently, the steady-st ate concentration of NC in skin during in vivo application of SOL was 6.6 times higher than corresponding in vitro data. In vivo P(C)s from SOL and GEL were however significantly lower than CL(CB)/A. These resu lts may be explained by the findings, using a laser Doppler flowmeter, that cutaneous blood flow was decreased by the application of MEW.