alexa Transdermal iontophoretic delivery of a liquid lipophilic drug by complexation with an anionic cyclodextrin.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Juluri A, Narasimha Murthy S

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Abstract Iontophoresis is now established as one of the methods of enhancing transdermal delivery of drugs. However, its application to enhance the delivery of highly lipophilic compounds is limited due to lack of any charge and poor water solubility of molecules. Propofol, a sedative and anesthetic drug was chosen as a model lipophilic drug in this study. Propofol was complexed with sulfobutyl ether-β-cyclodextrin (SCD), a β-cyclodextrin derivative carrying ionizable groups to render propofol amenable to iontophoresis. The phase solubility studies of propofol with SCD revealed an AL type curve indicating a stoichiometry of 1:1. The complex was characterized by UV-spectrophotometry and (1)HNMR. Transport studies were performed using Franz diffusion cells across porcine epidermis. The passive permeation flux of propofol was enhanced by fourfold due to complexation with SCD. Application of iontophoresis (0.5mA/cm(2)) to SCD-propofol solution enhanced the transport of propofol by an additional fourfold. The enhancement in the transport of propofol after complexation was found to be due to multiple mechanisms such as transport of intact complex, enhanced thermodynamic activity of drug at the interface and prolonged recovery of barrier disrupted due to iontophoresis. The pharmacokinetic studies were performed in Sprague-Dawley rats to assess the feasibility of transdermal iontophoretic delivery in vivo, of a lipophilic drug complexed with SCD. Copyright © 2014. Published by Elsevier B.V. This article was published in J Control Release and referenced in Journal of Bioequivalence & Bioavailability

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