Capillary zone electrophoresis for the estimation of transdermal iontophoretic mobility.
The objective of the study was to investigate the relationship between transdermal iontophoretic flux--specifically, the electromigratory component--and electrophoretic mobility as determined by capillary zone electrophoresis (CZE). First, the steady-state iontophoretic transport rates of a series of dipeptides across porcine skin were determined in vitro. Co-iontophoresis of acetaminophen was used to quantify the respective contributions of electroosmosis (EO) and electromigration (EM). Second, the electrophoretic mobilities of the dipeptides and three other cationic drugs (lidocaine, propranolol, and quinine) were determined, under equivalent experimental conditions, using CZE. Analysis of the transport data using the results of the CZE experiments revealed a linear dependence (r2 > 0.9) between EM flux and electrophoretic mobility. The CZE measurements also provided insight into the charge state of "zwitterionic" dipeptides, H-Glu-epsilon-Lys-OH and H-Tyr-Gln-OH, revealing that these molecules had partial net negative charges under the formulation conditions, accounting for the absence of anodal iontophoretic delivery. The results suggest that CZE might (i) enable identification of ionization states of complex molecules, (ii) serve as a preliminary screen to identify electrically mobile compounds suitable for iontophoretic delivery, and (iii) prove useful for predicting the EM contribution to transdermal iontophoretic flux.
Abla
Nada
N
School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
Geiser
Laurent
L
Mirgaldi
Myriam
M
Naik
Aarti
A
Veuthey
Jean-Luc
JL
Guy
Richard H
RH
Kalia
Yogeshvar N
YN
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D019075:Electrophoresis, Capillary; D066298:In Vitro Techniques; D007478:Iontophoresis; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008954:Models, Biological; D015394:Molecular Structure; D009995:Osmosis; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
D004151:Dipeptides; D000082:Acetaminophen; D008012:Lidocaine; D011433:Propranolol; D011803:Quinine