Flow-Through System Effects on in Vitro Analysis of Transdermal Systems

The development of transdermal therapeutic systems (TTS) often involves in vitro evaluation of formulations and prototypes using flow-through diffusion cells. The apparent flux obtained from such methodologies does not accurately represent the actual (intrinsic) permeation of the compound through the skin. Flow-through system parameters, i.e., fraction collector tube volume, receiver cell volume, flow rate, and sampling interval, modify the flux yielding an apparent flux. Both finite-dose flux profiles and infinite-dose diffusional lag times are modified by these parameters. In this study, a transfer function is derived which describes the effect of these parameters. The intrinsic flux is calculated from apparent flux data using the transfer function and experimental flow-through system parameters. This allows the calculation of permeant flux profiles devoid of modification by the experimental methodology.