On the search for in vitroin vivo correlations in the field of intra-articular drug delivery: Administration of sodium diatrizoate to the horse

Abstract

Development of suitable in vitro release models for formulation development as well as quality control purposes has to be initiated in the early design phase of injectable depots. Optimally, construction of an in vitro release model may lead to the establishment of in vitro in vivo correlations. By using a model compound (sodium diatrizoate, DTZ), the purpose of this study was to investigate the possibility of establishing in vitro in vivo relations between the DTZ disappearance profile obtained from the donor compartment of the rotating dialysis cell model and the joint disappearance profile following intra-articular administration. In vitro experiments were conducted by applying solutions of DTZ to the donor compartment. In the invivo experiments, five horses were subjected to both intravenous and intra-articular administration of an aqueous solution of 3.9mg DTZ/kg. A strong relation (R2=0.99) was obtained between the disappearance data from the donor compartment of the in vitro model and the disappearance data from the synovial fluid after intra-articular administration of DTZ. Furthermore, a relation (R2=0.91) between the appearance data obtained from the acceptor compartment and the deconvolved appearance serum data upon intra-articular administration of DTZ was obtained. The correlations obtained in this study hold promise that the rotating dialysis cell model has a role in the prediction of the intra-articular fate of drugs injected as solutions.