The Percutaneous Absorption And Pharmacokinetics Of Zaleplon

Zaleplon, one of excitomotors of ω₁ receptor of Benzodiazepine,was widely used for the treatment of insomnia in clinics. It has the special properties of fast effect, little adverse reaction. Although zaleplon is well absorbed, its absolute bioavailability is approximately 30% because it undergoes significant presystemic metabolism. There are several kinds of dosage forms marketed such as tablet and capsule. In order to avoid its presystemic metabolism by oral administration, the patch of zaleplon was formulated and studied.First, basic physical-chemical properties of drug were investigated. The results showed that zaleplon is little soluble in water and alcohol can improve its solubility. The partition coefficient of zaleplon in octanol/water is 1.55 which is near to the best ranger of LogP .So it can be considered to be a patch.In order to improve the steady-state flux of zaleplon, perpendicular diffusion cell was used to screen the permeation promoters. Vitro permeation experiments showed that the permeation kinetics of zaleplon across the rat skin was zero order and 10% Lauryl alcohol was selected to be the inhancer of the patch. Because it can increase the steady-state flux best.The method of evaporating organic solvent was established to make zaleplon the patch with acrylate PSA. Optimal formulation was acquired by orthogonal experiment. The fact that adhesion of patch was ideal was demonstrated by adhesion experiment.In order to observe the process using the zaleplon patch, we investigated the concentration of the drug in the serum and calculated. If the plasma concentration-time data was fit to two-compartment pharmacokinetic model,the C_max,K_a,V_c,T_1/(2α),T_1/(2β), CL,T_max,AUC were 0.62±0.12μg · mL^-1,0.68±0.20hr^-1,...