1: Pharm Res.  2003 Dec;20(12):1946-51.  

Transdermal delivery of timolol and atenolol using electroporation and
iontophoresis in combination: a mechanistic approach.

Denet AR, Ucakar B, Preat V.

Unite de Pharmacie Galenique, Universite Catholique de Louvain, UCL 7320, 1200
Brussels, Belgium.

PURPOSE: The purpose of this work was to study the effect of electroporation on
iontophoretic transport of two beta-blockers, timolol (lipophilic) and atenolol
(hydrophilic), and to have a better understanding of the mechanism of
combination. METHODS: The transdermal delivery of these beta-blockers through
human stratum corneum was studied in three-compartment diffusion cells. The
transport of mannitol was evaluated to assess the electroosmotic flow. RESULTS:
The iontophoretic transport of timolol was decreased by electroporation because
the high accumulation of the lipophilic cation timolol in the stratum corneum
resulted in a decrease of electroosmosis. In contrast, electroosmosis was not
affected by atenolol, and the iontophoretic transport of atenolol was increased
by electroporation. CONCLUSIONS: Using two different beta-blockers, we showed
that lipophilicity and positive charges affect the electrotransport of drugs.
Understanding the effect of the physicochemical properties of the drug, as well
as the electrical parameters, is thus essential for the optimization of
transdermal drug delivery by a combination of electroporation and iontophoresis.

PMID: 14725358 [PubMed - in process]