The effects of p-menthane monoterpenes and related compounds on the percutaneous absorption of propranolol hydrochloride across newborn pig skin: II. Infrared spectroscopic and thermal analysis investigations

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The effects of p-menthane monoterpenes and related compounds to increase the permeability of newborn pig stratum corneum were investigated using Fourier transformed infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). FTIR analysis on newborn pig stratum corneum that had been treated with hydro-alcoholic (40% ethanol v/v) mixtures of terpenes containing alcohols and ketones as functional groups revealed significant (p < 0.05) blue-shifts in the peak position of the C-H asymmetric stretching absorbance at 2918 cm -1 (carvacrol, carvone, R-carvone, S-carvone, menthol, menthone, menthyl acetate and thymol) and in the peak position of the symmetric stretching absorbances at 2850 cm-1 (carvacrol, menthyl acetate and thymol). Significant decreases in peak areas and heights of these peaks were also detected, with carvacrol consistently having the strongest effect, suggesting a disruption of the intercellular lipid bilayers. However, other terpenes (p-menthane, p-menthene, menthyl trifluoroacetate, γ-terpinene, α-terpinene, p-cymene, β-citronellol, menthyl chloride, citronellal, phellandrene and 1,4-cineole) on the other hand did not significantly change the C-H stretching absorbances. In addition, citronellal, citronellol, p-menthane and menthyl trifluoroacetate did not change either the peak areas and heights of these peaks. There were no significant differences in C-H asymmetric and symmetric stretching peak properties (peak position, peak area, peak height) between racemic menthol and its enantiomers and between racemic carvone and its enantiomers, indicating that the use of pure enantiomers or racemic mixtures of the same terpenes did not have a specific effect on the disruption of stratum corneum lipids. Furthermore, no peak shifts, peak height or peak area changes were observed in the amide I and amide II bands for all the terpenes studied, indicating that these terpenes do not modify the conformation of the proteins (keratin) in the stratum corneum. DSC experiments on representative terpenes (p-menthane, menthyl trifluoroacetate and carvacrol), after treatment of the stratum corneum with all selected terpenes, showed reductions in the endothermic DSC transition temperatures attributed to lipid melting (T2, 70°C and T3, 82°C). Again, carvacrol had the strongest effect. These FTIR and DSC findings suggest that terpenes containing hydroxyl or ketone groups interact with the highly ordered lipid structure of the stratum corneum, thus increasing membrane diffusivity. However, with the exception of the C-H asymmetric stretching peak position, changes in FTIR spectra or in the DSC thermograms of newborn pig stratum corneum caused by terpenes as penetration enhancers did not correlate highly with changes in skin permeability of propranolol hydrochloride (following linear or second order polynomial fit). This suggests that prediction of the penetration enhancing activity of the terpenes on the basis of CH-stretching peak properties alone is at best qualitative and that terpenes may have more than one mechanism of action.

Original languageEnglish
JournalS.T.P. Pharma Sciences
Issue number6
Pages (from-to)397-404
Number of pages8
Publication statusPublished - Nov 2003

    Research areas

  • Differential scanning calorimetry, Fourier transformed infrared spectroscopy, Terpenes

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