Influence of physicochemical properties on the in vitro skin permeation of the enantiomers, racemate, and eutectics of ibuprofen for enhanced transdermal drug delivery


  • Xudong Yuan,

    1. Department of Chemistry, Medical Technology, and Physics, School of Science, Monmouth University, West Long Branch, New Jersey 07764
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  • Anthony C. Capomacchia

    Corresponding author
    1. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602
    • Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602. Telephone: +706-542-5339; Fax: +706-542-5358
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Physicochemical properties of chiral ibuprofen are significant to formulation scientists because its enantiomers and eutectics possess lower melting points than its racemate. The influence of these properties on transdermal formulation development, especially the relative effect of lowered melting point, on skin permeation must be carefully assessed to provide the most efficacious formulation. Thermodynamic properties and crystalline structures of the enantiomers, eutectics, and racemate of chiral ibuprofen were investigated by differential scanning calorimetry and X-ray powder diffraction. The effect of melting point lowering on membrane permeation rates was mathematically modeled. Model was validated by in vitro skin permeation experiments using different preparations of racemic ibuprofen, enantiomer, and eutectic. Both enantiomer and eutectic formed a two-phase liquid system containing an emulsifiable aqueous phase and an oily phase in the presence of aqueous isopropyl alcohol (aIPA). The eutectic emulsion had the highest permeation rate, a 2.21-fold increase in flux compared with saturated aIPA solutions of the racemate with a 2.03-fold increase in flux. Results from the two-phase liquid system supported those from the mathematical models, albeit somewhat lower, and confirmed their use in predicting maximum flux utilizing thermodynamic data. Study data also supported the idea that eutectic formation, for ibuprofen and probably other chiral drugs, may be one of the best ways to develop topical formulations for improved percutaneous absorption to avoid the use of permeation enhancers or synthetically modifying chemical structure. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1957–1969, 2013