Distribution of khellin in excised human skin following iontophoresis and passive dermal transport

• Published in: Journal of controlled release Vol. 60; no. 2-3; pp. 261 - 268
• Main Authors: Marconi, B, Mancini, F, Colombo, P, Allegra, F, Giordano, F, Gazzaniga, A, Orecchia, G, Santi, P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05-08-1999; Elsevier
• Subjects: Biological and medical sciences; Cardiovascular system; Chromatography, High Pressure Liquid; Dermal iontophoresis; Diffusion; Electroosmosis; General pharmacology; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iontophoresis; Khellin; Khellin - pharmacokinetics; Medical sciences; Osmosis; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photochemotherapy; Skin - metabolism; Skin distribution; Time Factors; Vasodilator Agents - pharmacokinetics; Vasodilator agents. Cerebral vasodilators; Khellin; Skin distribution; Dermal iontophoresis; Photochemotherapy; Electroosmosis; Human; Pharmaceutical technology; Vasodilator agent; Biological transport; Permeation; Passive transport; Partition coefficient; Permeability; Iontophoresis; Distribution; Skin; Derm; Diffusion
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(99)00080-2

The aim of this work was to study in vitro khellin distribution into human skin after passive or iontophoretic transport. The experiments were performed on excised human skin, using vertical Franz-type diffusion cells. The effects of current application and reservoir pH were studied. At the end of the experiments the skin was sliced thinly and the drug was extracted and analyzed by HPLC. The results showed that khellin is able to penetrate through stratum corneum, to reach basal epidermis and upper dermis. The application time proved to be an important parameter. Current application (30 min; 0.5 mA/cm2), with a donor at pH 7.0, favored khellin accumulation even if the drug is not ionized. On the contrary, the use of a formulation at pH 3.2 inhibited drug accumulation. Leaving the drug reservoir in contact with the skin for 30 min after current application led to a dramatic increase of khellin concentration. A combination of dermal iontophoresis and passive diffusion is then a useful technique to govern khellin distribution in the skin.