The increase in life expectancy has led to a rise of musculoskeletal disorders. Calcium phosphate cements (CPCs), thanks to some amazing features such as the ability to harden in vivo, bioactivity, and resorbability, are promising candidates to treat these diseases, notwithstanding their poor mechanical properties. We aimed to synthesise pure and barium- or silicon-doped brushite-based CPCs loaded with piroxicam to study the effects of the substitution on physical-chemical and pharmaceutical properties before and after cement immersion in phosphate buffer for different time periods. Our results demonstrated that piroxicam became amorphous in the hardened cements. The dopants did not change the brushite structure or its lamellar morphology, while both Ba and Si additions improved the initial Young's modulus compared to the pure cement, and the opposite trend was observed for compressive strength. Both the compressive strength and the elastic modulus decreased for the samples immersed in solution compared to the non-immersed samples, with stabilisation as the number of days increased. After 7 days, the whole drug amount was released, with a slower and constant kinetic for the Ba-doped cements compared to the pure and Si-doped ones.