The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. I. General...

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.