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Pharmaceutical Research

, 24:186 | Cite as

Near Infrared Spectrometry for the Quantification of Human Dermal Absorption of Econazole Nitrate and Estradiol

  • Joseph P. Medendorp
  • Kalpana S. Paudel
  • Robert A. Lodder
  • Audra L. Stinchcomb
Research Paper

Abstract

Purpose

The purpose of this study was to demonstrate the use of near-infrared (NIR) spectrometry for the in vitro quantification of econazole nitrate (EN) and estradiol (EST) in human skin.

Methods

NIR spectra were collected from EN and EST powders to verify the presence of NIR chromophores. One percent EN cream, a saturated solution of EN, or 0.25% EST solution was applied to human skin. NIR spectra were collected and one-point net analyte signal (NAS) multivariate calibration was used to predict the drug concentrations. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts.

Results

NIR spectroscopy measured dermal absorption from saturated solutions of EN on human skin with an r2 = 0.990, standard error of estimation (SEE) = 2.46%, and a standard error of performance (SEP) = 3.55%, EN cream on skin with an r2 = 0.987, SEE = 2.30%, and SEP = 2.66%, and 0.25% solutions of EST on skin with an r2 = 0.987, SEE = 3.30%, and SEP = 5.66%. Despite low permeation amounts of both drugs through the stratum corneum into human tissue, the NIR signal-to-noise ratio was greater than three, even for the lowest concentrations.

Conclusion

NIR analyses paralleled the results obtained from HPLC, and thus could serve as a viable alternative for measuring the topical bioavailability/bioequivalence of different EN and EST formulations. Because these experiments were conducted in human tissue, this research suggests an all-optical in vivo method of measurement for dermal absorption could be developed.

Key words

chemometrics dermal drug absorption econazole estradiol net analyte signal  topical bioequivalence 

Notes

Acknowledgment

This research was sponsored by the Food and Drug Administration, contract number D3 922004.

References

  1. 1.
    L. K. Pershing, J. L. Nelson, J. L. Corlett, S. P. Shrivastava, D. B. Hare, and V. Shah. Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products. J. Am. Acad. Dermatol. 48(5):740–751 (2003).CrossRefPubMedGoogle Scholar
  2. 2.
    M. Kreilgaard, M. B. Kemme, J. Burggraaf, R. C. Schoemaker, and A. F. Cohen. Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics. Pharm. Res. 18(5):593–599 (2001).CrossRefPubMedGoogle Scholar
  3. 3.
    D. Wierenga and C. R. Eaton. Phases of product development—drug development and approval process. Alliance Pharmaceutical Corporation. Retrieved March 23, 2006. <http://www.allp.com/drug_dev.htm>.
  4. 4.
    F. Pirot, Y. N. Kalia, A. L. Stinchcomb, G. Keating, A. Bung, and R. H. Guy. Characterization of the permeability barrier of human skin in vivo. Proc. Natl. Acad. Sci. USA 94:1562–1567 (1997).CrossRefPubMedGoogle Scholar
  5. 5.
    A. L. Stinchcomb, F. Pirot, G. D. Touraille, A. L. Bunge, and R. H. Guy. Chemical uptake into human stratum corneum in vivo from volatile and non-volatile solvents. Pharm. Res. 16(8):1288–1293 (1999).CrossRefPubMedGoogle Scholar
  6. 6.
    M. B. Reddy, A. L. Stinchcomb, R. H. Guy, and A. L. Bunge. Determining dermal absorption parameters in vivo from tape strip data. Pharm. Res. 19(3):292–298 (2002).CrossRefPubMedGoogle Scholar
  7. 7.
    J. Medendorp, J. Yedluri, D. C. Hammell, T. Ji, R. A. Lodder, and A. L. Stinchcomb. Near infrared spectrometry for the quantification of dermal absorption of econazole nitrate and 4-cyanophenol. Pharm. Res. 23(4):835–843 (2006).CrossRefPubMedGoogle Scholar
  8. 8.
    A. Urbas, M. W. Manning, A. Daugherty, L. A. Cassis, and R. A. Lodder. Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE−/− mouse. Anal. Chem. 75:3650–3655 (2003).CrossRefPubMedGoogle Scholar
  9. 9.
    B. Dai, A. Urbas, and R. A. Lodder. Sensor batteries: implantable sensor batteries. NIR News 17(1):14–15 (2006).Google Scholar
  10. 10.
    Introduction to NIR technology. Analytical Spectral Devices, Inc. Retrieved February 12, 2006. http://www.asdi.com/ASD-600510_NIR-Introduction.pdf.
  11. 11.
    H. M. Boelens, W. T Kok, O. E. Noord, and A. K. Smilde. Performance optimization of spectroscopic process analyzers. Anal. Chem. 76:2656–2663 (2004).CrossRefPubMedGoogle Scholar
  12. 12.
    A. Lorber. Error propagation and figures of merit for quantification by solving matrix equations. Anal. Chem. 58:1167–1172 (1988).CrossRefGoogle Scholar
  13. 13.
    K. S. Booksh, and B. R. Kowalski. Theory of analytical chemistry. Anal. Chem. 66(15):782a–791a (1994).CrossRefGoogle Scholar
  14. 14.
    A. Lorber, K. Faber, and B. R. Kowalski. Net analyte signal calculation in multivariate calibration. Anal. Chem. 69(8):1620–1626 (1997).CrossRefGoogle Scholar
  15. 15.
    W. Fountain, K. Dumstorf, A. E. Lowell, R. A. Lodder, and R. J. Mumper. Near-infrared spectroscopy for the determination of testosterone in thin-film composites. J. Pharm. Biomed. Anal. 33(2)1:181–189 (2003).CrossRefPubMedGoogle Scholar
  16. 16.
    R. A. Lodder, M. Selby, and G. Hieftje. Detection of capsule tampering by near-infrared reflectance analysis. Anal. Chem. 59:1921–1930 (1987).CrossRefGoogle Scholar
  17. 17.
    I. T. Jolliffe. Principal Component Analysis. Springer, Berlin Heidelberg New York, 2002.Google Scholar
  18. 18.
    R. Leardi and L. Norgaard. Sequential application of backward interval partial least squares and genetic algorithms for the selection of relevant spectra regions. J. Chemom. 18:486–497 (2004).CrossRefGoogle Scholar
  19. 19.
    O. E. Noord. Elimination of uninformative variables for multivariate calibration. Anal. Chem. 68:3851–3858 (1996).CrossRefGoogle Scholar
  20. 20.
    K. C. Moon, R. C. Wester, and H. I. Maibach. Diseased skin models in the hairless guinea pig skin: in vivo percutaneous absorption. Dermatologica 180:8–12 (1999).CrossRefGoogle Scholar
  21. 21.
    R. Panchagnula, K. Stemmer, and W. A. Ritschel. Animal models for transdermal drug delivery. Methods Find. Exp. Clin. Pharmacol. 19:335–341 (1997).PubMedGoogle Scholar
  22. 22.
    L. L. Ferry, G. Argentieri, and D. H. Lochner. The comparative histology of porcine and guinea pig skin with respect to iontophoretic drug delivery. Pharm. Acta Helv. 70:43–56 (1995).CrossRefPubMedGoogle Scholar
  23. 23.
    X. Jia, Z. Zhu, and C. Li. Immune and biochemical analysis of protein of homogenates of three different kinds of skin. Zhonghua Zheng Xing Shao Shang Waike Za Zhi 12(1):51–53 (1996).Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Joseph P. Medendorp
    • 1
  • Kalpana S. Paudel
    • 1
  • Robert A. Lodder
    • 1
  • Audra L. Stinchcomb
    • 1
  1. 1.Department of Pharmaceutical SciencesCollege of Pharmacy, University of KentuckyLexingtonUSA

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