Release characteristics of anionic drug compounds from liquid crystalline gels: III. Chemical and iontophoretic enhancement of delivery across non-rate-limiting membranes

Abstract

This paper investigates the release and transport of a range of anionic drugs from liquid crystalline gels using chemical and physical enhancement techniques. Previous papers [Fitzpatrick, D., Corish, J., 2005. Release characteristics of anionic drug compounds from liquid crystalline gels. I. Passive release across non-rate limiting membranes. Int. J. Pharm. 301, 226–236; Fitzpatrick, D., Corish, J., 2006. Release characteristics of anionic drug compounds from liquid crystalline gels. II. The effects of ion pairing and buffering on the passive delivery of anionic drugs across non rate-limiting membranes. Int. J. Pharm.] have reported on the passive release profiles and those resulting from the incorporation of a chemical enhancer in the vehicle. This paper investigates the behaviour of the system under iontophoretic conditions and also under those of combined physical and chemical enhancement. The data presented here are directly comparable to previous work by Nolan et al. [ Nolan, L.M.A., Corish, J., Corrigan, O.I., Fitzpatrick, D., 2003. Iontophoretic and chemical enhancement of drug delivery. Part I. Across artificial membranes. Int. J. Pharm. 12, 41–55; Nolan, L.M.A., Corish, J., Corrigan, O.I., Fitzpatrick, D., 2006. Combined effects of iontophoretic and chemical enhancement on drug delivery. II. Transport across human and hairless murine skin. Int. J. Pharm., submitted for publication] which investigated the behaviour of cationic compounds under analogous conditions. The iontophoretic release of diclofenac in the presence of model enhancers is thoroughly investigated. It is also shown that a range of anionic drug molecules undergo an electrochemical change during the course of the experiments which leads to their poor detection. This may be a factor in the under reporting of iontophoretic delivery of anionic drugs in the literature. However, it has been shown that the transport of the drugs is greatly enhanced by the application of an iontophoretic current. Results of combined enhancement studies provide a positive basis on which to proceed with in vitro studies of the system across human skin.