Transport characteristics in a novel in vitro release model for testing the performance of intra-articular injectables

Abstract

There is a need for bio-predictive and well-characterized in vitro release models in the development of intra-articular depot formulations. Here, the commercially-available Scissor system, a membrane-based two-compartment release testing instrument, was applied to characterize the transport and release of the drug diclofenac employing conditions intended to mimic transport in the synovial joint. The fate of hyaluronic acid and human serum albumin, the main bio-relevant components incorporated in the system, was investigated. A promising strategy for providing sustained drug release upon intra-articular administration are lipid-based preformulations forming non-lamellar liquid crystalline phases in situ. The usefulness of the Scissor system for investigating the initial drug release from these delivery systems was evaluated. The diclofenac release rate upon injection of an aqueous solution was influenced by the composition of the injection site matrix, i.e. the hyaluronic acid content. Hyaluronic acid and human serum albumin were found to escape from the donor compartment into the acceptor medium through the employed polycarbonate membrane. Sustained diclofenac release was obtained by formation of highly viscous liquid crystalline phases upon injection of the lipid-based preformulations. The study shows the feasibility and potential of the Scissor system for testing initial release of intra-articular depot formulations of low-molecular-weight drug compounds.