Enhanced transdermal delivery of evodiamine and rutaecarpine using microemulsion

Abstract

Objective: The purpose of this study was to improve skin permeation of evodiamine and rutaecarpine for transdermal delivery with microemulsion as vehicle and investigate real-time cutaneous absorption of the drugs via in vivo microdialysis. Methods: Pseudoternary phase diagrams were constructed to evaluate microemulsion regions with various surfactants and cosurfactants. Nine formulations of oil in water microemulsions were selected as vehicles for assessing skin permeation of evodiamine and rutaecarpine in ex vivo transdermal experiments. With a microdialysis hollow fiber membrane implanted in the skin beneath the site of topical drug administration, dialysis sampling was maintained for 10 hours and the samples were detected directly by high performance liquid chromatography. Real-time concentrations of the drugs in rat skin were investigated and compared with those of conventional formulations, such as ointment and tincture. Furthermore, the drugs were applied to various regions of the skin using microemulsion as vehicle. Results: In ex vivo transdermal experiments, cutaneous fluxes of evodiamine and rutaecarpine microemulsions were 2.55-fold to 11.36-fold and 1.17-fold to 6.33-fold higher, respectively, than those of aqueous suspensions. Different drug loadings, microemulsion water content, and transdermal enhancers markedly influenced the permeation of evodiamine and rutaecarpine. In microemulsion application with in vivo microdialysis, the maximum concentration of the drugs (evodiamine: 18.23 ± 1.54 ng/mL; rutaecarpine: 16.04 ± 0.69 ng/mL) were the highest, and the area under the curve 0-t of evodiamine and rutaecarpine was 1.52-fold and 2.27-fold higher than ointment and 3.06-fold and 4.23-fold higher than tincture, respectively. A greater amount of drugs penetrated through and was absorbed by rat abdominal skin than shoulder and chest, and a reservoir in the skin was found to supply drugs even after the microemulsion was withdrawn. Conclusion: Compared to conventional formulations, higher cutaneous fluxes of evodiamine and rutaecarpine were achieved with microemulsion. Based on this novel transdermal delivery, the transdermal route was effective for the administration of the two active alkaloids.

Developments in drug delivery of bioactive alkaloids derived from traditional Chinese medicine

“…The permeation rates of MS-loading huperzine A and ligustrazine phosphate were both markedly enhanced in comparison to the free drugs in treatment of amnesia (Shi et al., 2012a ). Moreover, both of evodiamine and rutaecarpine filled into MS showed larger bioavailabilities than the tinctures (Zhang et al., 2011 ). NLCs, consisting of solid and liquid lipids, are derived from SLNs (Tiwari & Pathak, 2011 ; Liu & Feng, 2015 ).…”

Preparation and evaluation of microemulsion-based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides

“…A close relationship between the hydration effect of the stratum corneum and the dermal permeation has previously been reported (20), and the thermodynamic activity of drugs in MEs was a significant driving force behind the release and penetration of drugs into the skin (20,21). The thermodynamic activity of drugs in ME with lower surfactant mixture content was demonstrated to be an important driving force for the release and the penetration of the drug into skin (22,23). The decreased concentration of surfactant in dispersed systems may also increase the rate of drug release and its permeation in the skin (24,25).…”