Correlation between in vivo microdialysis pharmacokinetics and ex vivo permeation for sinomenine hydrochloride transfersomes with enhanced skin absorption.

ABSTRACT

Transdermal drug delivery systems have drawn increasing attention in recent decades. Estimation of the correlation between ex vivo permeation and in vivo absorption (EVIVC) is an indispensable issue in the research and development of transdermal pharmaceutical products. In this paper, sinomenine hydrochloride (SH) transfersomes (SHTs) were prepared with sodium deoxycholate as edge activator, while SH liposomes (SHLs) were prepared as a control preparation. The transdermal permeation characteristics differences between them were explored by an ex vivo skin permeation experiment with Franz diffusion cell and an in vivo skin/blood pharmacokinetic experiment facilitated by double-sited microdialysis sampling technique. The curves of percentage absorbed versus time (absorption curves) under the skin and in the blood were plotted according to the percentages calculated by the deconvolution approach with the application of Wagner-Nelson model, and were correlated with the ex vivo permeation curves to evaluate a level A correlation, while a level C correlation evaluation was conducted based on the in vivo steady-state blood concentration (Css) and the ex vivo steady-state transdermal permeation rate. The ex vivo permeation test indicated that the cumulative transdermal permeated amount of SH at 36 h in SHTs was about 1.7 times of that in SHLs. The skin pharmacokinetic data showed that the Css and AUC0-t of SHTs were about 8.8 and 8.0 times of those of SHLs, respectively, and the MRT0-t of SHTs was shorter. The blood pharmacokinetic data showed that the Css and AUC0-t of SHTs were about 3.7 and 2.9 times of those of SHLs, respectively. The in vivo absorption curves were correlated well with the ex vivo permeation curves. The squares of correlation coefficient (R2) for SHTs and SHLs were 0.9153 and 0.9355 respectively in the skin, were 0.8536 and 0.7747 respectively in the blood. As to level C EVIVC, there was no significant difference between the predicted Css from ex vivo and the measured Cssin vivo. The transfersomes can be employed as effective vehicles to promote the transdermal absorption of SH, and it is feasible to predict the in vivo skin/blood pharmacokinetic properties of SHLs and SHTs based on the ex vivo skin permeation characteristics.