Biorelevant release testing of biodegradable microspheres intended for intra-articular administration

Characterization of controlled release formulations used for intra-articular (IA) drug administration is challenging. Bio-relevant synovial fluids (BSF), containing physiologically relevant amounts of hyaluronic acid, phospholipids and proteins, were recently proposed to simulate healthy and osteoarthritic conditions. This work aims to evaluate the performance of different controlled release formulations of methylprednisolone (MP) for IA administration, under healthy and disease states simulated conditions. Microspheres differed in grade of poly(lactide-co-glycolide) and in the theoretical drug content (i.e. 23 or 30% w/w). Their performance was compared with the commercially available suspension of MP acetate (MPA). Under osteoarthritic state simulated condition, proteins increased the MPA release and reduced the MPA hydrolysis rate, over 48 h. Regarding microspheres, the release patterns over 40 days were significantly influenced by the composition of BSF. The pattern of the release mechanism and the amount released was affected by the presence of proteins. Protein concentration affected the release and the concentration used is critical, particularly given the relevance of the concentrations to target patient populations, i.e. patients with osteoarthritis.