Characterization of the rotating dialysis cell as an in vitro model potentially useful for simulation of the pharmacokinetic fate of intra-articularly administered drugs

Abstract

The rotating dialysis cell consisting of a donor and an acceptor compartment with volumes of 10 and 1000 ml, respectively, separated by a dialysis membrane is proposed as an in vitro model potentially useful for simulation of the events influencing drug residence time in the knee joint cavity after intra-articular instillation. The purpose of this study was to characterize the rotating dialysis cell model with respect to basic model and drug related factors affecting the rate of drug appearance in the acceptor phase after initial instillation of the solutes into the donor cell. A total of 15 model compounds were included in the study and it was revealed that the transport processes were governed by (i) the volume of the donor solution and (ii) the molecular weight of the diffusants. A relationship between the donor volume-independent permeability coefficient and the molecular weight of the diffusants has been established. Additionally, the model was robust with release kinetics being insensitive to changes in pH, ionic strength, viscosity of the release medium, and revolution speed of the donor cell. The characteristics of the rotating dialysis cell model suggest that it may be a useful tool in the design of innovative depot injectables in the area of local joint delivery.