Near-infrared spectrometry for the quantification of dermal absorption of econazole nitrate and 4-cyanophenol

Joseph Medendorp, Jhansi Yedluri, Dana C. Hammell, Tao Ji, Robert A. Lodder, Audra L. Stinchcomb

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Purpose. The purpose of this study was to demonstrate the utility of near-infrared (NIR) spectroscopy for the in vitro quantification of econazole nitrate (EN) and 4-cyanophenol (4-CP) in hairless guinea pig skin. Methods. NIR spectra were collected from each of the following: EN and 4-CP powders, EN and 4-CP in solution, and skin samples following topical exposure to either 4-CP in water or EN in propylene glycol and topical creams. To predict drug concentration from NIR spectra, principal component regression (PCR), interval PCR, and uninformative variable elimination PCR were each used with a leave-one-out cross-validation, and results were compared. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts. Results. NIR results matched the HPLC results for the quantification of 4-CP and EN in skin exposed to saturated solutions and topical creams with an r 2 > 0.90, a standard error of estimation <7.0%, and a standard error of performance <8.0%. Conclusion. This experiment demonstrated that NIR closely parallels results obtained from tissue extraction and HPLC analysis, proving its potential utility for the rapid and noninvasive determination of topical bioavailability/bioequivalence of EN and quantification of the model chemical 4-CP. Investigation of drugs in human skin is now justified.

Original languageEnglish
Pages (from-to)835-843
Number of pages9
JournalPharmaceutical Research
Volume23
Issue number4
DOIs
StatePublished - Apr 2006

Bibliographical note

Funding Information:
This research was sponsored by the Food and Drug Administration, contract number D3922004.

Keywords

  • Dermal drug absorption
  • Interval principal component regression (iPCR)
  • PCR-uninformative variable elimination (PCR-UVE)
  • Topical bioequivalence

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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