Preparation and evaluation of biodegradable flubiprofen gelatin micro-spheres for intra-articular administration

Purpose: A controlled release delivery system that localizes flurbiprofen (FP) in synovial joint is prefered to treat inflammation in rheumatoid arthritis (RA). The purpose of this study is to develop and characterize FP-loaded gelatin microspheres and evaluate FP plasma concentrations following intra-articular injection into healthy rabbits.

Methods: Flurbiprofen gelatin microspheres (FP-GMS) were prepared by a emulsion-congealing method. The RP-HPLC method was established to determine the FP concentraion in plasma. The particle size of FP-GMS with optimized formulation was 2.5?～?12.3?µm with a mean size of gelatin microspheres of 7.53?µm. The drug loading efficiency was 5.02% (w/w). The dissolution profile of the FP-GMS was depicted by Higuchi kinetics.

Results: The half time for 50% release of FP from FP-GMS (t₅₀) was 5.58?h. A total of 96% original FP was remained in the microspheres after being stored under 75% humidity and 37°C for 3 months. The pharmacokinetics study demonstrated that the mean resident time (MRT) of FP in the FP-GMS group was prolonged vs. the injection group significantly (p?<?0.01) after intra-articular administration into healthy rabbit hind joints. The T_p of FP-GMS group was prolonged by 2.03-times and the C_max was decreased by 5.57-times vs. that of the injection group, respectively. The FP plasma concentration in FP-GMS was 8-fold higher than that of the FP injection group at 8?h. In addition, FP was rapidly cleared from blood circulation within 8?h with the injection group while FP was retained for more than 24?h with the FP-GMS group.

Conclusions: These data indicate that the simple emulsion-congealing method can be used to encapsulate water soluble drugs such as FP for the treatment of inflammatory disease within the joint cavity.