| Autor: |
Welin-Berger, Katayoun, Neelissen, Jan A.M., Emanuelsson, Britt-Marie, Björnsson, Marcus A., Gjellan, Kirsti |
| Zdroj: |
Journal of Pharmaceutical Sciences; February 2003, Vol. 92 Issue: 2 p398-406, 9p |
| Abstrakt: |
The aim of this study was to evaluate the relevance of the in vitropermeation method used at our laboratory in predicting in vivodermal and transdermal absorption. Two different emulsions, a submicron oil-in-water (o/w) emulsion and a semisolid water-in-oil (w/o) emulsion, containing a model compound were investigated. The in vitropermeation rate of the compound from these emulsions was measured using static diffusion cells with human skin as membrane. The emulsions were allowed to remain in contact with the skin in the donor chamber for 15, 60, and 240min. The study was monitored for 240min and the steady state flux was calculated. The systemic concentration of the compound was measured in vivoas a function of time after dermal application to healthy volunteers with 15 and 60min of application. A short-lasting i.v. infusion study in healthy volunteers was used to simulate the i.v. bolus dose. Numerical convolution was used to predict the in vivoplasma concentration of the compound while the in vivoabsorption rate of the compound was estimated using numerical deconvolution. To establish correlation, the predicted in vivoflux was compared with the corresponding observed in vitroparameter after adjusting for the lag time. No major differences were seen in the systemic plasma levels between the two emulsions, which is in close agreement with the steady state flux measured in vitro. A linear correlation representing a point-to-point relationship was established for each of the investigated formulations and application times. The longer application time was predicted more accurately for both emulsions. |
| Databáze: |
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