Transdermal absorption of celiprolol and bisoprolol in human skin in vitro

Two beta-blockers, celiprolol and bisoprolol, which have a priori interesting properties to be considered in the search of a possible candidate for a transdermal therapeutic system (TTS) were assayed. In vitro permeation studies were conducted at 32 +/- 1 degrees C across human abdominal skin. Franz glass diffusion cells were used in the static mode (n = 7). The amounts of drug permeated from receptor solution at predetermined times were analysed by reversed-phase HPLC with UV detection. From the penetration profiles obtained for each drug, the main permeation parameters, permeability coefficient (K-p), flow (J) and lag time (T-lag) were estimated as a measure of the intrinsic permeability across human skin. Mean K-p value was higher for celiprolol (0.59 +/- 0.22 cm h(-1)) than bisoprolol (0.27 +/- 0.15 x 10(-3) cm h(-1)), although both were very low. Mean J value was also higher for celiprolol (2.72 +/- 0.92 mu g h(-1) cm(-2)) than bisoprolol (1.19 +/- 0.60 mu g h(-1) cm(-2)), Mean T-lag value was 20.43 +/- 8.43 h for celiprolol and 32.13 +/- 39.34 h for bisoprolol. Both provide plasma concentrations at steady state that would be far from their therapeutic concentration. The results indicate the need for appropriate enhancers to improve their diffusion across human skin. (C) 1998 Elsevier Science B.V. All rights reserved.