ACCURATE DETERMINATION OF SKIN FLUX FROM FLOW-THROUGH DIFFUSION CELL DATA

Purpose. The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flo w-through diffusion cell may be accurately and easily determined by ac counting for the accumulation in the receiver chamber. Methods. Mathem atical modeling, applied to transdermal diffusion, was used to calcula te receiver concentration data for single layer and bilayer membranes. The data were interpreted using two appar J(app1) has been used exten sively in the ent flux values, J(app1), and J(app2). J(app1) has been used extensively in the literature, but did not account for accumulati on in the receiver. J(app2) did take the accumulation into considerati on. Results. The results confirm that, generally, J(app1) values were not accurate estimates of the intrinsic flux. J(app2) Values were sign ificantly more accurate, especially prior to the maximum in receiver c oncentration. Conclusions. J(app2) was an accurate measurement of intr insic flux over the entire experimental time period, except at time ze ro. It was more accurate because it accounted for solute accumulation in the receiver compartment. The accuracy of the J(app2) approximation was practically independent of receiver volume, flow rate and donor v olume. For very slowly permeating drugs, or a very small receiver volu me combined with a high flow rate, the J(app1) estimate accurately ref lected the intrinsic flux. Early time data were required to properly a ccount for accumulation in the receiver cell. If such data were not av ailable, the inverse Laplace method of determining intrinsic flux the J(app2) calculation.