Skip to Content
Merck
  • In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.

In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.

Journal of medicinal chemistry (2007-02-16)
Giorgio Ottaviani, Sophie Martel, Pierre-Alain Carrupt
ABSTRACT

The development of in silico and in vitro tools to estimate or predict the passive human skin permeation and distribution of new chemical entities, useful in dermal drug delivery, in absorption studies of toxic compounds, and in the cosmetics industry, is presented. In vitro permeation parameters were measured using the artificial membrane PAMPA-skin. The Volsurf approach was then applied to extract pertinent descriptors from molecular interaction fields characterizing the molecular structure of tested compounds. Two useful three-dimensional solvatochromic models able to predict PAMPA permeation parameters directly from the molecular structure were obtained using the partial least squares analysis. The models also provide valuable information to understand the link between physicochemical and structural properties of tested compounds and their interactions with the artificial membrane PAMPA-skin and can be useful to rapidly estimate their permeation through the human skin.

MATERIALS
Product Number
Brand
Product Description

Supelco
Betamethasone, VETRANAL®, analytical standard
Supelco
Atrazine, analytical standard
Supelco
Phenol solution, certified reference material, 500 μg/mL in methanol
Sigma-Aldrich
Acridine, ≥96.5% (HPLC)
Supelco
Phenol solution, 5000 μg/mL in methanol, certified reference material
Sigma-Aldrich
Benzoic acid, purified by sublimation, ≥99%
Sigma-Aldrich
Thymol, FCC, FG
Supelco
Melting point standard 121-123°C, analytical standard
Supelco
Atrazine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Benzoic acid, Standard for quantitative NMR, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
(S)-(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid, 98%
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
Supelco
Thymol, analytical standard
Sigma-Aldrich
Phenol, puriss. p.a., ACS reagent, reag. Ph. Eur., 99.0-100.5%
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Sigma-Aldrich
4-Bromophenol, 99%
Sigma-Aldrich
Benzoic acid, ACS reagent, ≥99.5%
Sigma-Aldrich
Phenol, unstabilized, ReagentPlus®, ≥99%
Sigma-Aldrich
2,4,6-Trichlorophenol, 98%
Sigma-Aldrich
Phenylacetic acid, 99%
Sigma-Aldrich
Phenol, ACS reagent, ≥99.0%
Supelco
Atrazine, PESTANAL®, analytical standard
Sigma-Aldrich
2-Naphthol, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
Phenol, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.5-100.5% (GC)
Supelco
Benzoic acid, reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Phenol, puriss., ≥99.5% (GC), meets analytical specification of Ph. Eur., BP, USP, crystalline (detached)
Supelco
Phenol, PESTANAL®, analytical standard
Supelco
Naproxen, VETRANAL®, analytical standard
Sigma-Aldrich
Benzoic acid, natural, ≥99.5%, FCC, FG
Sigma-Aldrich
Phenol, unstabilized, purified by redistillation, ≥99%