title: Silicone elastomer uptake method for determination of free 1-alkyl-2-pyrrolidone concentration in micelle and hydroxypropyl-beta-cyclodextrin systems used in skin transport studies.
abstract: 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-beta-cyclodextrin (HPbetaCD). The free CS, HP, OP, DP, and DoP aqueous concentrations in the DSPE micelle and HPbetaCD 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 approximately 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.
authors: ZARS Pharma, 1142 W. 2320 S., Salt Lake City, UT 84119, USA. kwarner@zars.com
authors: Kevin S
authors: KS
authors: Warner
authors: Dalia S
authors: DS
authors: Shaker
authors: Sarah
authors: S
authors: Molokhia
authors: Qingfang
authors: Q
authors: Xu
authors: Jinsong
authors: J
authors: Hao
authors: William I
authors: WI
authors: Higuchi
authors: S Kevin
authors: SK
authors: Li
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003345:Corticosterone / Q000008:administration & dosage / Q000493:pharmacokinetics; D005079:Excipients / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008823:Micelles; D010539:Permeability; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D012826:Silicone Elastomers; D012867:Skin / Q000033:anatomy & histology / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects*; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D005079:Excipients; D008823:Micelles; D011760:Pyrrolidinones; D012826:Silicone Elastomers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003345:Corticosterone