On the search for in vitro in vivo correlations in the field of intra-articular drug delivery: administration of sodium diatrizoate to the horse.

This research study focuses on investigating the potential to establish in vitro (in the lab) and in vivo (in a living organism) correlations by using a model compound, Sodium Diatrizoate (DTZ), in the field of intra-articular (inside the joint) drug delivery. Their findings showed a high correlation between the disappearance of DTZ from an in vitro model and from the joint fluid following intra-articular administration of DTZ, implying that the in vitro model might predict the fate of drugs injected as solutions in an intra-articular manner.

Objective and Methodology

• The goal of this research was to determine whether there is a relationship between the disappearance profile of a model compound (DTZ) in vitro, and its disappearance profile in vivo, both following intra-articular administration.
• To achieve this, the researchers conducted in vitro experiments using the DTZ, applying its solutions to a rotating dialysis cell model. The disappearance of the DTZ from the donor compartment of this model was tracked and analyzed.
• In addition, in vivo experiments were performed on five horses, where an aqueous solution of DTZ was administered both intravenously and intra-articularly. The disappearance of DTZ from the synovial fluid, which is found in the joints, was monitored and compared with the in vitro results.

Findings

• The disappearance of DTZ in vitro significantly correlated (R(2)=0.99) with its disappearance in the synovial fluid post-intra-articular administration. In other words, how the DTZ behaved and disappeared inside the joint of a living organism was nearly identical to how it disappeared in the laboratory model.
• A further correlation (R(2)=0.91) was found between the appearance of the DTZ in the acceptor compartment of the in vitro model and the appearance serum data upon intra-articular administration of the compound.

Conclusion and implications

• These findings indicate that the rotating dialysis cell model may be a valuable tool to predict how drugs will behave once injected as solutions directly into the joints (intra-articular administration). This can particularly aid in formulation development and quality control during the early design phase of injectable depots.