The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. I. General characteristics.
A single-pass perfused rabbit ear was employed as the model for studying percutaneous absorption of clonazepam in an open perfusion system. Clonazepam at 1.5% concentration (w/w) was suspended in a gel containing 1% (w/w) neutralized Carbopol 934 vehicled by a 50% water solution of propylene glycol and applied to the skin, in a thermostatically controlled chamber, after 10 min pretreatment with a lauryl alcohol enhancer. At 32 degrees C, the amount of clonazepam which diffused into the effluent after a 3 h lag phase was constant for 3 h and the flux averaged 0.486 mcg/h/cm2, whereas at 25 degrees C, the flux averaged 0.424 mcg/h/cm2. The amount of drug diffusing into the effluent was a function of the contact surface area and was independent of the rate of perfusion up to values of 1 ml/min. The apparent diffusion coefficient, Ds, and the partition coefficient, KM, were 2.75/10(6)/cm/h and 5.21, respectively.
Celesti
L
L
Department of Pharmaceutical Chemistry and Technology, University of Siena, Italy.
Murratzu
C
C
Valoti
M
M
Sgaragli
G
G
Corti
P
P
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002998:Clonazepam / Q000493:pharmacokinetics*; D004058:Diffusion; D004431:Ear, External / Q000378:metabolism*; D004487:Edema / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D014677:Pharmaceutical Vehicles; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D012869:Skin Absorption / Q000502:physiology*
D014677:Pharmaceutical Vehicles; D011506:Proteins; D002998:Clonazepam