Effect of selected fluorinated drugs in a "ringing" gel on rheological behaviour and skin permeation.
The purpose of the present study was to investigate the influence of different drugs exhibiting different solubility on the viscoelastic properties and on the skin diffusion profile of a ringing gel. In a preliminary rheology study with the placebo gel predominating elastic properties were confirmed and a temperature influence was indicated. Fluconazole, fludrocortisone-acetate, flumethasone-pivalate, flutamide and flufenamic-acid each 1% (w/w) were incorporated into the preparation and oscillatory measurements were performed at temperatures of 25, 28, 32 and 37 degrees C. In all drug containing formulations a high elastic G' value predominated the viscous G'' value. The highest G' value could be obtained with the incorporated flumethasone-pivalate. Additionally in almost all cases the G' values decreased with increasing temperature compared to the placebo gel. Additionally in vitro standard diffusion experiments using Franz-type cells and porcine skin were performed. Following rank order of the cumulative drug release after 48 h was obtained: fluconazole>flufenamic-acid>flumethasone-pivalate>flutamide>fludrocortisone-acetate. Furthermore an excellent chemical stability of all incorporated drugs was confirmed over 10 weeks.
Höller
Sonja
S
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, Vienna, Austria.
Valenta
Claudia
C
D000818:Animals; D004058:Diffusion; D004355:Drug Stability; D015725:Fluconazole / Q000737:chemistry / Q000493:pharmacokinetics; D005438:Fludrocortisone / Q000737:chemistry / Q000493:pharmacokinetics; D005439:Flufenamic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D005443:Flumethasone / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D017611:Fluorine Compounds / Q000737:chemistry*; D005485:Flutamide / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D009821:Oils / Q000737:chemistry; D010232:Paraffin / Q000737:chemistry; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012881:Skin Temperature; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013552:Swine; D014783:Viscosity; D014867:Water / Q000737:chemistry
D017611:Fluorine Compounds; D005782:Gels; D009821:Oils; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D014867:Water; C005565:flumethasone pivalate; D005439:Flufenamic Acid; D005485:Flutamide; D010232:Paraffin; C015418:paraffin oils; D015725:Fluconazole; D005443:Flumethasone; D005438:Fludrocortisone