AIMTo establish an in situ perfused pig ear model for percutaneous absorption.

METHODSThe in situ perfused pig ear model for percutaneous absorption consisted of artificial gas, sample chamber, constant flow pump, constant temperature system, polytetrafluorethylene connective tube, porcine ear vein, porcine ear skin and special laminar flow apparatus. The perfused system viability was assessed by glucose utilization and lactate production. Ketoprofen isopropyl ester and methyl salicylate was used for validating this model. The concentrations of perfused sample were measured by HPLC.

RESULTSGlucose utilization and lactate production showed that this model was viable till 7 h. Ketoprofen isopropyl ester was completely metabolized to ketoprofen in situ in perfused pig ear model. The steady cumulative amount (Q) of ketoprofen from permeation and metabolism was linear with time (t), the equation of ketoprofen formation was Q = -0.024 + 0.120t, the rate of ketoprofen formation was 0.120 microgram.cm-2.h-1. Methyl salicylate was partially metabolized to salicylic acid. The steady cumulative amount (Q) of methyl salicylate from permeation was linear with time (t), the permeation equation of methyl salicylate was Q = -3.809 + 6.129t, the permeation rate of metyl salicylate was 6.129 micrograms.cm-2.h-1. The steady cumulative amount (Q) of salicylic acid from metabolism was also linear with time (t), the formation equation of salicylic acid was Q = -1.785 + 0.879t, the formation rate of salicylic acid was 0.879 microgram.cm-2.h-1.

CONCLUSIONThe in situ pig ear vein perfused model is a novel easy-handing and cost-efficient technique for percutaneous absorption and skin metabolism.