Percutaneous penetration of methyl nicotinate from ointments using the laser Doppler technique: bioequivalence and enhancer effects.
Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry "Topical dermatologic corticosteroids: In Vivo bioequivalence" applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.
Remane
Yvonne
Y
Institute for Pharmacy, Department of Pharmaceutical Technology, University of Hamburg, Bundesstr. 45, 20146, Hamburg, Germany.
Leopold
Claudia S
CS
Maibach
Howard I
HI
D000293:Adolescent; D000328:Adult; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D005026:Ethylene Glycols / Q000008:administration & dosage; D006801:Humans; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008875:Middle Aged; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D009824:Ointments; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption; D013810:Therapeutic Equivalency
D005026:Ethylene Glycols; D009539:Nicotinic Acids; D009824:Ointments; D014677:Pharmaceutical Vehicles; C008473:methyl nicotinate; C010111:carbitol; D004121:Dimethyl Sulfoxide