Dose-dependent enhancement effects of azone on skin permeability.
In vitro permeability experiments have been combined with differential scanning calorimetry (DSC) studies in an attempt to address the dose-dependent influence of Azone on the permeability coefficients of solutes for hairless mouse stratum corneum. A spray technique was developed to deliver uniformly and quantitatively small amounts of Azone to the stratum corneum. Permeability data obtained for several model solutes of varying lipophilicity suggest lipid fluidization and polar route enhancement as the mechanisms of action for Azone. Alkanols and steroids, both of which are enhanced primarily by lipid fluidization, had different degrees of relative enhancement. This provides evidence that the stratum corneum barrier is heterogeneous, rather than a homogeneous slab barrier. Two effects of Azone on the stratum corneum were detected by DSC. A decrease in the area and a shift to lower temperatures were noted for the lipid endotherms with increasing doses of Azone. A lipid fluidizing effect would qualitatively account for the increases in the permeability coefficients noted for more lipophilic solutes. The stratum corneum keratin endotherm also appears to be altered in the presence of Azone. It is possible that alteration of the keratin structure could lead to the development of polar routes in the stratum corneum.
Lambert
W J
WJ
Department of Pharmaceutics, University of Utah, Salt Lake City 84112.
Higuchi
W I
WI
Knutson
K
K
Krill
S L
SL
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002855:Chromatography, Thin Layer; D003345:Corticosterone / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012869:Skin Absorption / Q000187:drug effects*; D013696:Temperature
D001381:Azepines; C035229:laurocapram; D003345:Corticosterone; D006854:Hydrocortisone