Estimating maximal in vitro skin permeation flux from studies using non-sink receptor phase conditions

Yousef, Shereen, Liu, Xin, Mostafa, Ahmed, Mohammed, Yousuf, Grice, Jeffrey E., Anissimov, Yuri G., Sakran, Wedad and Roberts, Michael S. (2016) Estimating maximal in vitro skin permeation flux from studies using non-sink receptor phase conditions. Pharmaceutical Research, 33 9: 2180-2194. doi:10.1007/s11095-016-1955-8


Author Yousef, Shereen
Liu, Xin
Mostafa, Ahmed
Mohammed, Yousuf
Grice, Jeffrey E.
Anissimov, Yuri G.
Sakran, Wedad
Roberts, Michael S.
Title Estimating maximal in vitro skin permeation flux from studies using non-sink receptor phase conditions
Formatted title
Estimating maximal in vitro skin permeation flux from studies using non-sink receptor phase conditions
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 1573-904X
0724-8741
Publication date 2016-09-01
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s11095-016-1955-8
Open Access Status Not yet assessed
Volume 33
Issue 9
Start page 2180
End page 2194
Total pages 15
Place of publication New York, NY, United States
Publisher Springer New York LLC
Language eng
Abstract This study explored the impact of non-sink receptor conditions on the in vitro skin permeation test (IVPT) and sought to estimate equivalent sink condition IVPT data.
Formatted abstract
Purpose: This study explored the impact of non-sink receptor conditions on the in vitro skin permeation test (IVPT) and sought to estimate equivalent sink condition IVPT data.

Methods: Simulated diffusion model and experimental IVPT data were generated for ethyl salicylate across human epidermal membranes in Franz diffusion cells using six different receptor phases, with a 10 fold variation in ethyl salicylate solubility.

Results: Both simulated and experimental IVPT – time profiles were markedly affected by receptor phase solubility and receptor sampling rates. Similar sink condition equivalent estimated maximum fluxes were obtained by nonlinear regression and adjustment of linear regression estimates of steady state flux for relative saturation of the receptor phase over time for the four receptor phases in which the ethyl salicylate was relatively soluble. The markedly lower steady - state fluxes found for the other two phases in which ethyl salicylate was less soluble was attributed to an aqueous solution boundary layer effect.

Conclusions: Non-sink receptor phase IVPT data can be used to derive equivalent sink receptor phase IVPT data provided the receptor phase solubility and hydrodynamics are sufficient to minimise the impact of aqueous diffusion layers on IVPT data.
Keyword Aqueous boundary layer
Ethyl salicylate
In vitro permeation test
Receptor medium
Saturated solubility
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1049906
U01FD005232
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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