The effect of surfactants on the skin penetration of diazepam.
The percutaneous permeation of diazepam was investigated in rat skin after application of a water-propylene glycol (50:50% v/v) using a diffusion cell technique. The effect of various surfactants (sodium lauryl sulfate (SLS), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with different concentrations on skin permeability were evaluated. Flux, K(p), lag time and enhancement ratios (ERs) of diazepam were measured over 10 h and compared with control sample (containing no surfactant). Furthermore, diazepam solubility in presence of surfactants was determined. The in vitro permeation experiments with rat skin revealed that the surfactant enhancers varied in their ability to enhance the flux of diazepam. Benzalkonium chloride which possessed the highest lipophilicity (logP=1.9) among cationic surfactants provided the greatest enhancement for diazepam flux (7.98-fold over control). CTAB (logP<1) at a concentration of 1% w/w exhibited no significant increase in flux of diazepam compared to control (1.16-fold over control). The results also showed that the highest ER was obtained in presence of 1% w/w surfactant with the exception of SLS and CTAB. The increase in flux at low enhancer concentrations is normally attributed to the ability of the surfactant molecules to penetrate the skin and increase its permeability. Reduction in the rate of transport of the drug present in enhancer systems beyond 1% w/w is attributed to the ability of the surfactant to form micelles and is normally observed only if interaction between micelle and the drug occurs. The results showed that the nature of enhancer greatly influences cutaneous barrier impairment.
Shokri
J
J
Drug Applied Research Centre, School of Pharmacy, Tabriz Medical Sciences University, Tabriz, Iran.
Nokhodchi
A
A
Dashbolaghi
A
A
Hassan-Zadeh
D
D
Ghafourian
T
T
Barzegar Jalali
M
M
D000279:Administration, Cutaneous; D000465:Algorithms; D000818:Animals; D003975:Diazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D005079:Excipients; D018757:GABA Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D011409:Propylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013501:Surface-Active Agents / Q000494:pharmacology*
D005079:Excipients; D018757:GABA Modulators; D007202:Indicators and Reagents; D011409:Propylene Glycols; D013501:Surface-Active Agents; D003975:Diazepam