Lontophoretic delivery of apomorphine in vitro: physicochemic considerations.
OBJECTIVE
To examine the mechanisms of transdermal iontophoretic delivery of apomorphine.


METHODS
Anodal iontophoresis of R-apomorphine across human stratum corneum was determined in vitro. The effects on the flux of the following parameters were studied: stability of drug, pH of donor solution, concentration of NaCl, and type of Na+ co-ions.


RESULTS
Ascorbic acid was effective to prevent apomorphine degradation. The iontophoretic transport of apomorphine was strongly influenced by the pH of the donor formulation. Increasing the pH from 3 to 6 resulted in an increase in the iontophoretic apomorphine flux from 27.9+/-4.4 nmol/cm2*h to 78.2+/-6.9 nmol/cm2*h. Upon decreasing NaCl concentration from 8 to 2 g/L, the iontophoretic flux was not significantly changed. Replacing NaCl in the donor formulation by tetraethylammonium chloride or tetrabutylammonium chloride resulted in 1.3 fold greater steady-state flux.


CONCLUSIONS
For optimized apomorphine iontophoretic delivery, a constant pH of the donor formulation is of great importance. The results suggest that although flux enhancement during iontophoresis is largely due to the electrical potential gradient, secondary effects, such as convective flow and electroosmosis may also contribute.
Li
G L
GL
Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, The Netherlands.
Danhof
M
M
Bouwstra
J A
JA
D000279:Administration, Cutaneous; D000975:Antioxidants / Q000737:chemistry; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000737:chemistry*; D001058:Apomorphine / Q000008:administration & dosage* / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis
D000975:Antioxidants; D000978:Antiparkinson Agents; D001058:Apomorphine