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• W1969966404 abstract "The transdermal iontophoretic delivery of Leuprolide, a nonapeptide LHRH agonist was studied with the aim of understanding the mechanisms of iontophoresis. Permeation studies were carried out at pH 4.5 and 7.2, at which the average ionic valence of the drug molecule was roughly 2 and 1, respectively. Heat‐separated human epidermal membrane was subjected to constant voltage within the range of 250 to 1000 mV during the iontophoretic phase. Iontophoretic enhancement at pH 7.2 was greated than at 4.5. A model for iontophoretic enhancement was developed that takes into consideration the membrane alterations caused by iontophoresis depicted as increased porosity and the permeation through lipid pathways of the stratum corneum. Model‐based evaluation yielded that first, the porosity increased with the applied voltage to as much as three times the original at 1000 mV. Second, the lipid pathways contributed approx. 20% to the total permeation during the passive phase. Third, the electro‐osmotic flow contributed significantly to the enhancement and its direction was from anode to cathode at pH 7.2 and the opposite at pH 4.5. The magnitude of the electro‐osmotic flow was at pH 4.5 somewhat lower than at pH 7.2. Addition of a negatively charged water soluble peptide, Acetyl leucine leucinolyl phosphate as an adjuvant led to twofold increase in the enhancement factor at pH 4.5 and a decrease in the magnitude of the electro‐osmotic flow from cathode to anode. Repeated iontophoretic applications of 250 mV on the same skin specimen resulted in same enhancement every time and did not cause any barrier alterations when applied for 1 h every 24 h, which was not the case if the duration between the two iontophoretic applications was only 3 h." @default.
• W1969966404 created "2016-06-24" @default.
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• W1969966404 date "2003-01-01" @default.
• W1969966404 modified "2023-09-23" @default.
• W1969966404 title "In Vitro Transdermal Iontophoretic Delivery of Leuprolide—Mechanisms Under Constant Voltage Application" @default.
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• W1969966404 doi "https://doi.org/10.1002/jps.10257" @default.
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