Previous investigations in our laboratory demonstrated how the polar head group and alkyl chain of amphiphilic chemical skin permeation enhancers contribute to enhancer potency. In those studies enhancers with n-alkyl chain lengths of eight or less were investigated. In order to investigate enhancers with longer n-alkyl chain lengths, enhancer-solubilizing agents should be considered. Corticosterone (CS) flux enhancement along the lipoidal pathway of hairless mouse skin (HMS) was determined with the enhancers 1-hexyl- (HP), 1-octyl- (OP), 1-decyl- (DP), and 1-dodecyl-2-pyrrolidone (DoP) solubilized in 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy(polyethylene glycol-2000] (DSPE) micelles or in hydroxypropyl-β-cyclodextrin (HPβCD). The free CS, HP, OP, DP, and DoP aqueous concentrations in the DSPE micelle and HPβCD systems were determined using a partitioning method. Comparisons of the enhancer potencies based on the free concentration of the enhancers revealed a nearly semi-logarithmic linear relationship between enhancer potency and the carbon number of the alkyl chain length with a slope of ∼0.55. The observed n-alkyl chain length dependency in the aqueous phase is consistent with the hydrophobic effect. This study shows that longer chain enhancers may be studied by employing a solubilizing system, and free enhancer concentration in these systems can be determined with the aid of the silicone elastomer uptake method.
Article
Silicone Elastomer Uptake Method for Determination of Free 1-Alkyl-2-Pyrrolidone Concentration in Micelle and Hydroxypropyl-b-Cyclodextrin Systems Used in Skin Transport Studies
Pharmaceutical Science and Research
Document Type
Article
Publication Date
1-1-2008
Disciplines
Abstract
Citation Information
Warner, K. S., Shaker, D. S., Molokhia, S., Xu, Q., Hao, J., Higuchi, W. I., & Li, S. K. (2008). Silicone elastomer uptake method for determination of free 1‐alkyl‐2‐pyrrolidone concentration in micelle and hydroxypropyl‐β‐cyclodextrin systems used in skin transport studies. Journal of Pharmaceutical Sciences, 97(1), 368-380.
The Version of Record is available from the publisher at http://onlinelibrary.wiley.com/doi/10.1002/jps.21094/pdf.
Journal of Pharmaceutical Sciences, Vol. 97, 368–380 (2008)
© 2007 Wiley-Liss, Inc. and the American Pharmacists Association