D J Harrison1, K Knutson. 1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112, USA.
Abstract
PURPOSE: The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS: Mathematical modeling, applied to transdermal diffusion, was used to calculate receiver concentration data for single layer and bilayer membranes. The data were interpreted using two apparent flux values, Japp1 and Japp2. Japp1 has been used extensively in the literature, but did not account for accumulation in the receiver. Japp2 did take the accumulation into consideration. RESULTS: The results confirm that, generally, Japp1 values were not accurate estimates of the intrinsic flux. Japp2 values were significantly more accurate, especially prior to the maximum in receiver concentration. CONCLUSIONS: Japp2 was an accurate measurement of intrinsic flux over the entire experimental time period, except at time zero. It was more accurate because it accounted for solute accumulation in the receiver compartment. The accuracy of the Japp2 approximation was practically independent of receiver volume, flow rate and donor volume. For very slowly permeating drugs, or a very small receiver volume combined with a high flow rate, the Japp1 estimate accurately reflected the intrinsic flux. Early time data were required to properly account for accumulation in the receiver cell. If such data were not available, the inverse Laplace method of determining intrinsic flux was preferable to the Japp2 calculation.
PURPOSE: The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS: Mathematical modeling, applied to transdermal diffusion, was used to calculate receiver concentration data for single layer and bilayer membranes. The data were interpreted using two apparent flux values, Japp1 and Japp2. Japp1 has been used extensively in the literature, but did not account for accumulation in the receiver. Japp2 did take the accumulation into consideration. RESULTS: The results confirm that, generally, Japp1 values were not accurate estimates of the intrinsic flux. Japp2 values were significantly more accurate, especially prior to the maximum in receiver concentration. CONCLUSIONS: Japp2 was an accurate measurement of intrinsic flux over the entire experimental time period, except at time zero. It was more accurate because it accounted for solute accumulation in the receiver compartment. The accuracy of the Japp2 approximation was practically independent of receiver volume, flow rate and donor volume. For very slowly permeating drugs, or a very small receiver volume combined with a high flow rate, the Japp1 estimate accurately reflected the intrinsic flux. Early time data were required to properly account for accumulation in the receiver cell. If such data were not available, the inverse Laplace method of determining intrinsic flux was preferable to the Japp2 calculation.