IONTOPHORETIC DELIVERY OF APOMORPHINE I - IN-VITRO OPTIMIZATION AND VALIDATION

Purpose. To investigate the feasibility of transdermal iontophoretic d elivery of apomorphine in patients with Parkinson's disease, transderm al transport rates were optimized and validated across human stratum c orneum and freshly dermatomed human skin in vitro. Method. In all expe riments R-apomorphine hydrochloride was applied in the anodal compartm ent. The effect on the flux of the following parameters was studied, u sing a flow through transport cell: current density, pH, concentration , ionic strength, osmolarity, buffer strength, temperature and skin ty pe. Results. Transdermal transport of apomorphine was directly control led by the presence or absence of current. Passive delivery was minima l and no depot effect was observed. A linear relationship was found be tween current density and steady-state flux. At room temperature the l ag time was 30 to 40 minutes. A maximal steady-state flux was obtained when the donor concentration approached maximum solubility. By increa sing the temperature of the acceptor chamber to 37 degrees C, the stea dy-state flux was increased by a factor of 2.3 and the lag time decrea sed to +/-3 minutes. No effect of osmolarity and buffer strength, and only a small effect of ionic strength and pH on the transport rate wer e observed. The flux through dermatomed human skin was decreased compa red to stratum corneum. This effect was shown not to be caused by skin metabolism. Conclusions. The results obtained in vitro indicate that the iontophoretic delivery of apomorphine can be controlled and manipu lated accurately by the applied current. The in vitro flux furthermore depends on the donor composition, temperature and skin type. Under op timized conditions, transport rates resulting in therapeutically effec tive plasma concentrations are feasible, assuming a one to one in vitr o/in vivo correlation.