Shereen Yousef1,2, Xin Liu1, Ahmed Mostafa1,2, Yousuf Mohammed1, Jeffrey E Grice1, Yuri G Anissimov3, Wedad Sakran2, Michael S Roberts4,5. 1. Therapeutics Research Centre, School of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, Brisbane, Australia. 2. Departments of Pharmaceutics and Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Helwan, Egypt. 3. School of Natural Sciences, Griffith University, Brisbane, Australia. 4. Therapeutics Research Centre, School of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, Brisbane, Australia. m.roberts@uq.edu.au. 5. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. m.roberts@uq.edu.au.
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.
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.
Authors: Christofori M R R Nastiti; Thellie Ponto; Eman Abd; Jeffrey E Grice; Heather A E Benson; Michael S Roberts Journal: Pharmaceutics Date: 2017-09-21 Impact factor: 6.321
Authors: Heather A E Benson; Jeffrey E Grice; Yousuf Mohammed; Sarika Namjoshi; Michael S Roberts Journal: Curr Drug Deliv Date: 2019 Impact factor: 2.565