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.
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.
Warner
Kevin S
KS
ZARS Pharma, 1142 W. 2320 S., Salt Lake City, UT 84119, USA. kwarner@zars.com
Shaker
Dalia S
DS
Molokhia
Sarah
S
Xu
Qingfang
Q
Hao
Jinsong
J
Higuchi
William I
WI
Li
S Kevin
SK
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*
D005079:Excipients; D008823:Micelles; D011760:Pyrrolidinones; D012826:Silicone Elastomers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003345:Corticosterone