Electrically enhanced and controlled drug delivery through buccal mucosa

Aleksandra E. Mościcka-Studzińska 1Kinga Czarnecka Tomasz Ciach 1

1. Warsaw University of Technology, Faculty of Chemical and Process Engineering, L.waryńskiego 1, Warszawa 00-645, Poland

Abstract

The majority of drugs is administrated orally. Patient compliance is very high with this administration route, but bioavailability is often low - from the reason of first pass hepatic effect (e.g. Naltrexone NaCl) and unpredictable - from variable absorption conditions in digestive system.  This popular drug form may also lead to negative gastrointestinal side effects (e.g. Galantamine HBr) or to cirrhosis additionally. Because patients usually don’t accept injections there is a necessity to work out efficient, painless drug administration technique which will provide a high bioavailability of active substance and reduce the side effects. There is a need to determine new rout of administration and to work out therapeutic system which makes possible to optimize doses and provides an improvement of life comfort for sufferings.

The aim of this work was to determine the possibility of transmucosal iontophoretic  delivery of cationic drug and to investigate ex vivo Galantamine HBr and Naltreksone HCl administration via buccal mucosa by applying the iontophoresis and to define of initial donor drug concentration (in the presence and without of competitive cations) and current density influences on drug flux.

The ex vivo iontophoresis through porcine buccal mucosa were conducted at room temperature in a horizontal two-chamber permeation cell with silver/silver chloride electrodes. Chambers contents were stirred to prevent concentration polarization. The donor was a drug solution in artificial saliva buffer or in distilled water. The acceptor was a phosphate buffer saline. The drug concentration was measured by spectrophotometry.

Drug transfer rate was estimated as a molar flux. The increase of current resulted in the increase of drug flux - it was a straight dependence in the range of 0.4 – 1.5 mA/cm2, but over this range it deviated from a straight line. From first and second Faraday’s laws the theoretical maximum drug flux was calculated for the system in which the charge is carried by drug cations only. This value was compared to measured drug flux. The result was shown as a drug transport current efficiency which depends on current density. This function reaches plateau above the value 1.5 mA/cm2. The drug flux was independent on drug concentration in the absence of competitive cations in donor solution in whole range of solubility; however the drug flux was an exponential function of drug concentration in the presence of small inorganic cations, which came from a buffer.

The present work shows that it is possible to deliver a therapeutic dose of drug using the iontophoresis in spite of that the percentage current efficiency reached only the level of 2-10 % under the experimental conditions. Iontophoresis enables control and enhance drug delivery through buccal mucosa. The initial drug concentration and current density provide an easy way to control the rate of drug delivery. These results suggest possibility of design and construction of an intraoral implant for systemic controlled drug delivery.

This work is a part of IntelliDrug Project and was financially supported by European Commission, 6th Framework Programme (www.biomedlab.ichip.pw.edu.pl).

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Presentation: Oral at VI Multidyscyplinarna Konferencja Nauki o Leku, by Aleksandra E. Mościcka-Studzińska
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2008-03-14 19:21
Revised:   2009-06-07 00:48
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