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Percutaneous Penetration Enhancement in Vivo Measured by Attenuated Total Reflectance Infrared Spectroscopy

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Abstract

A novel application of attenuated total reflectance IR Spectroscopy (ATR-IR) was used to monitor the outer several microns of the stratum corneum (SC) and, thereby, demonstrate enhanced percutaneous absorption in vivo in man. 4-Cyanophenol (CP) as a model permeant yielded a unique IR signal, distinct from those of the stratum corneum and the vehicle components. CP was administered for 1, 2, or 3 hr as a 10% (w/v) solution either in propylene glycol or in propylene glycol containing 5% (v/v) oleic acid. The absorbance at 2230 cm−1, which corresponded to C≡N bond stretching, diminished significantly faster when CP was codelivered with oleic acid. An IR absorbance due primarily to propylene glycol at 1040 cm−1 (C–O stretching) also disappeared more quickly following application of the enhancer-containing solution. In addition, only the formulations with oleic acid induced a higher wavenumber shift in the frequency of the asymmetric C–H bond stretching absorbance. This change indicates increased lipid-chain disorder, the mechanism by which oleic acid is believed to cause enhanced drug transport across the stratum corneum. Therefore, ATR-IR permits one to examine noninvasively the kinetics, extent, and mechanism of percutaneous penetration enhancement in vivo in human subjects.

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REFERENCES

  1. R. H. Guy and J. Hadgraft. Selection of drug candidates for transdermal drug delivery. In J. Hadgraft and R. H. Guy (eds.), Transdermal Drug Delivery: Developmental Issues and Re-search Initiatives, Marcel Dekker, New York, 1989, pp. 59–81.

    Google Scholar 

  2. R. J. Scheuplein and I. H. Blank. Permeability of the skin. Physiol. Rev. 51:701–747 (1971).

    Google Scholar 

  3. P. M. Elias. Plastic wrap revisited. Arch. Dermatol. 123:1405–1406 (1987).

    Google Scholar 

  4. W. J. Albery and J. Hadgraft. Percutaneous absorption: In vivo experiments. J. Pharm. Pharmacol. 31:140–147 (1979).

    Google Scholar 

  5. I. H. Blank. Factors which influence the water content of the stratum corneum. J. Invest. Dermatol. 18:433–440 (1952).

    Google Scholar 

  6. H. D. Onken and C. A. Moyer. The water barrier in human epidermis. Physical and chemical nature. Arch. Dermatol. 87:584–590 (1963).

    Google Scholar 

  7. P. M. Elias, E. R. Cooper, A. Korc, and B. A. Brown. Percutaneous transport in relation to stratum corneum structure and lipid composition. J. Invest. Dermatol. 67:291–301 (1981).

    Google Scholar 

  8. W. P. Smith, M. S. Christensen, and S. Nacht. Effect of lipids on the aggregation and permeability of human stratum corneum. J. Invest. Dermatol. 78:7–11 (1982).

    Google Scholar 

  9. M. L. Williams and P. M. Elias. The extracellular matrix of stratum corneum: Role of lipids in normal pathological function. CRC Crit. Rev. Ther. Drug Carrier Syst. 3:95–122 (1987).

    Google Scholar 

  10. S. H. White, D. Mirejovsky, and G. I. King. Structural features of mouse stratum corneum determined by X-ray diffraction. Biochemistry 27:3725–3732 (1988).

    Google Scholar 

  11. K. Knutsen, R. O. Potts, D. B. Guzek, G. M. Golden, J. E. McKie, W. J. Lambert, and W. I. Higuchi. Macro-and molecular physical-chemical considerations in understanding drug transport in the stratum corneum. J. Control. Rel. 2:67–87 (1985).

    Google Scholar 

  12. G. M. Golden, J. E. McKie, and R. O. Potts. Role of stratum corneum lipid fluidity in transdermal drug flux. J. Pharm. Sci. 76:25–28 (1987).

    Google Scholar 

  13. G. M. Golden, D. B. Guzek, A. H. Kennedy, J. E. McKie, and R. O. Potts. Stratum corneum lipid phase transitions and water barrier properties. Biochemistry 26:2382–2388 (1987).

    Google Scholar 

  14. V. H. W. Mak, R. O. Potts, and R. H. Guy. Oleic acid concentration and effect in human stratum corneum: Non-invasive determination by attenuated total reflectance infrared spectroscopy. J. Control. Rel. 12:67–75 (1990).

    Google Scholar 

  15. R. O. Potts, D. B. Guzek, R. R. Harris, and J. E. McKie. A noninvasive, in vivo technique to quantitatively measure water concentration of the stratum corneum. Arch. Dermatol. Res. 277:489–495 (1985).

    Google Scholar 

  16. D. A. W. Bucks. Prediction of Percutaneous Penetration, Ph.D. thesis, University of California, San Francisco, 1989.

  17. N. J. Harrick. Internal Reflection Spectroscopy, Harrick Scientific Corp., 1979.

  18. D. G. Cameron, J. K. Kauppinen, D. J. Moffatt, and H. H. Mantsch. Precision in condensed phase vibrational spectroscopy. Appl. Spectrosc. 36:245–250 (1982).

    Google Scholar 

  19. B. W. Barry. Dermatological Formulations: Percutaneous Absorption, Marcel Dekker, New York, 1983.

    Google Scholar 

  20. K. A. Walters. Penetration enhancers and their uses in transdermal therapeutic systems. In J. Hadgraft and R. H. Guy (eds.), Transdermal Drug Delivery: Developmental Issues and Research Initiatives, Marcel Dekker, New York, 1989, pp. 197–246.

    Google Scholar 

  21. H. L. Casal and H. H. Mantsch. Polymorphic phase behavior of phospholipid membranes studied by infrared spectroscopy. Biochim. Biophys. Acta 779:381–401 (1984).

    Google Scholar 

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Authors and Affiliations

  1. Departments of Pharmacy and Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, 94143

    Vivien H. W. Mak & Richard H. Guy

  2. Dermal Therapeutics Group, Pfizer Central Research, Groton, Connecticut, 06340

    Vivien H. W. Mak & Russell O. Potts

Authors
  1. Vivien H. W. Mak
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  2. Russell O. Potts
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  3. Richard H. Guy
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Mak, V.H.W., Potts, R.O. & Guy, R.H. Percutaneous Penetration Enhancement in Vivo Measured by Attenuated Total Reflectance Infrared Spectroscopy. Pharm Res 7, 835–841 (1990). https://doi.org/10.1023/A:1015960815578

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