In situ formed suspensions for local sustained action of celecoxib following intra-articular administration

摘要

In vitro release of celecoxib from in situ formed suspensions intended for intra-articular (IA) delivery has been investigated using a rotating dialysis cell model. The appearance of celecoxib in the acceptor phase after instillation of a concentrated drug solution in PEG 400 into the small aqueous donor compartment was followed by reverse phase HPLC. After an initial fast release a constant flux was observed. Likewise, a similar constant flux was found for a preformed aqueous suspension of the drug. The highly comparable fluxes observed indicate that the solid celecoxib precipitated from the in situ formed suspension exhibited an aqueous solubility similar to that of parent celecoxib used for the preformed aqueous suspension. Results from the in vivo experiments in horses revealed that solid materials was observed within the synovium of the radiocarpal joint 10 days after IA administration of an in situ formed suspension of celecoxib. In the field of IA drug administration the in situ suspension forming drug delivery principle appears promising for the provision of local prolonged drug action. However, for clinical use the reproducibility of the precipitation step in the biological matrix may still need improvement.