Background: The objective of the present study was to investigate the combinative effect of ball milling and solvent displacement method on size reduction of Celecoxib particles. Celecoxib is a poorly water soluble cyclooxygenase 2 inhibitor which has a wide range of therapeutic applicability.

Methods: Microparticles were developed via solvent displacement method followed by planetary ball milling. In order to obtain an optimized size and size distribution of Celecoxib microparticles various factors were evaluated; the role of solvent type, type and concentration of stabilizer, milling effect, and the effect of milling duration were the most important factors studied during the present investigation.

Results: All the obtained formulations were in micron range that the smallest particles had the size of 1.76 μm and the formulation containing the largest particles was of 8.30 μm by volume mean diameter. Both solvent displacement and milling methods are common and potential approaches in order to formulate micron scaled particles.

Conclusion: The combination of these two methods generates a synergistic effect which leads to smaller particle size and a narrow size distribution. Celecoxib microparticles have the potential to use as promising delivery systems to treat various disease and malignancies.