Enabling the drug combination of celecoxib through a spherical co-agglomeration strategy with controllable and stable drug content and good powder properties

Combining celecoxib with other chemopreventive drugs is a promising method of chemoprevention for cancer, especially for colorectal cancer. However, the traditional drug combination approaches are restricted with highcost apparatus, complex and numerous unit operations. This work aims to develop an efficient spherical coagglomeration strategy for celecoxib in combination with lovastatin, which can achieve drug combination in a single crystallization unit. The ternary solvent system was determined based on molecular simulation, and then a stable spherical agglomeration process was developed through the design of molar fraction of anti-solvent (MFA) and stirring rate to produce spherical agglomerates with high sphericity (84.2-89.9 %) and narrow size distribution. On this basis, celecoxib-benzoic acid spherical co-agglomerates were designed to form a complete spherical co-agglomeration strategy, which includes solvent system selection, spherical agglomeration and spherical co-agglomeration. Finally, celecoxib-lovastatin spherical co-agglomerates with synergistic efficacy were successfully produced by this strategy, with controllable and stable drug content (fluctuation < 2.7 %), good powder properties, and improved tabletability.