Transdermal delivery of timolol by electroporation through human skin

The purpose was to achieve therapeutic fluxes of timolol by transdermal delivery using skin electroporation. The transdermal transport of timolol through human stratum corneum was studied in three compartment diffusion cells. The electrodes, buffer composition and pulse conditions were optimized. Timolol maleate concentration in the donor compartment was 40 mg/ml. Square wave pulses were applied. Electroporation enhanced the transdermal transport of timolol by 1-2 orders of magnitude as compared to passive diffusion. Even though the current application lasted for only 10 s, the transdermal transport remained high after pulsing for at least 6 h. Higher fluxes were obtained with Pt electrodes close to the skin and a phosphate buffer. 10 pulses of 400 V-10 ms were more efficient than 10 low voltage-long duration pulses. Therapeutic fluxes of timolol (>50 microg/cm(2) per h) through human stratum corneum were achieved by electroporation.