Osteoarthritis (OA), the most common form of arthritis, is characterized by chronic inflammation, degeneration of articular cartilage and whole joints. Local delivery by intra-articular (IA) injection of small molecules is an established treatment to relieve pain and improve joint motion, requiring month-lasting release of therapeutic drug doses. We incorporated anti-inflammatory drug celecoxib in poly (D, L-lactic acid) microparticles using two spray-drying approaches – either as a solid drug solution or embedded as milled nano drug. Differential scanning calorimetry, X-ray powder diffraction, electron microscopy and in vitro drug release allowed comparison of the microparticles. Both types resulted in spherical particles ranging from 20 to 40 μm mean size, with high drug loadings (10 % to 50 % w/w) and entrapment efficiencies > 80 %. However, after 90 days, in vitro celecoxib release from nano drug embedded microparticles presented a significantly slower release in comparison to drug in solution microparticles, attributed to the presence of stabilized amorphous drug. No cytotoxicity was observed in human articular synoviocytes and PGE release was fully suppressed at low doses of both microparticulate systems. This study provides techniques to release high drug loads over months in a tunable manner, providing valuable options for the IA management of osteoarthritis.Copyright © 2020. Published by Elsevier B.V.