Correlation between stratum corneum/water-partition coefficient and amounts of flufenamic acid penetrated into the stratum corneum

J Pharm Sci. 2002 Aug;91(8):1915-21. doi: 10.1002/jps.10183.

Abstract

The stratum corneum of various donors differs in particular in the composition of the lipoidal phase. Considering the drug amounts penetrating into the stratum corneum a simple methodology to correlate these differences in the stratum corneum composition with the drug amounts detectable within the stratum corneum is desirable. Penetration experiments investigating several incubation times were carried out with three different skin flaps using the Saarbruecken penetration model and the lipophilic model drug flufenamic acid. The drug amounts within the stratum corneum were obtained with the tape-stripping technique, while the drug amounts present in the deeper skin layers were achieved by cryosectioning. The stratum corneum/water-partition coefficient was determined with the same three skin flaps to characterize the lipoidal stratum corneum phase in general, and the differences were attributed to the different amounts of ceramides and sterols. In addition, for the lipophilic drug flufenamic acid, a direct linear correlation was found between the stratum corneum/water-partition coefficients and the drug amounts penetrated into the stratum corneum for all investigated time intervals (correlation coefficients of r(30 min) = 0.998, r(60 min) = 0.998 and r(180 min) = 0.987). In contrast to the stratum corneum/water-partition coefficients, the determination of a corresponding relationship for the stratum corneum and the deeper skin layers failed due to the reason that steady-state conditions could not be achieved for the deeper skin layers during the investigated time intervals. In summary, the stratum corneum/water-partition coefficients offer the possibility to predict drug amounts within the stratum corneum of different donor skin flaps without a time consuming determination of the lipid composition of the stratum corneum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Chemical Phenomena
  • Chemistry, Physical
  • Female
  • Flufenamic Acid / pharmacokinetics*
  • Humans
  • In Vitro Techniques
  • Lipids / chemistry
  • Skin / chemistry
  • Skin / metabolism*
  • Skin Absorption*
  • Solubility

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipids
  • Flufenamic Acid