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  • Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.

Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.

Expert opinion on drug delivery (2014-06-21)
Qi-en Che, Peng Quan, Mao Mu, Xinfu Zhang, Hanqing Zhao, Yu Zhang, Song You, Yi Xiao, Liang Fang
ABSTRACT

The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers. The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated in vitro using side-by-side diffusion cells. With the melting temperature-membrane transport model, the flux ratio of enantiomer/racemate was calculated from their thermodynamic properties obtained by differential scanning calorimetry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) study was performed to evaluate the interaction between the enantiomers and the SC. New fluorescent probes were designed and utilized in confocal laser scanning microscopy (CLSM) study for visualization of the enantioselective permeation of the enantiomers through the intact rabbit skin. The flux of (S)-ibuprofen through normal skin was significantly higher than that of (RS)-ibuprofen and (R)-ibuprofen (p < 0.05), whereas in damaged skin, there was no significant difference (p > 0.05). The predicted flux ratio of (S)-ibuprofen/(RS)-ibuprofen (2.50) was in close agreement with the experimentally determined ratio (2.48). These results were supported by ATR-FTIR and CLSM studies that indicated that a chiral environment of the skin led to the enantioselective permeation of enantiomers. The chiral nature of the SC and the different physicochemical properties of the enantiomers should be taken into account in the assessment of different skin permeability of the racemate and enantiomers. The synthetic fluorescent probes used in this study could visualize the enantioselective permeation of the chiral compounds across the skin.

MATERIALS
Product Number
Brand
Product Description

Supelco
Ibuprofen sodium salt, ≥98% (GC)
Supelco
Ibuprofen, Pharmaceutical Secondary Standard; Certified Reference Material
Ibuprofen for peak identification, European Pharmacopoeia (EP) Reference Standard
USP
Ibuprofen, United States Pharmacopeia (USP) Reference Standard
Supelco
Ibuprofen
Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Sigma-Aldrich
Ibuprofen, meets USP testing specifications
Ibuprofen, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(S)-(+)-Ibuprofen, ReagentPlus®, 99%
Supelco
Ibuprofen solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®