Improving oral bioavailability and tabletability of celecoxib by preparing its three cocrystals

Celecoxib (Cel) has extremely poor aqueous solubility, low bioavailability, and unsatisfactory powder mechanical properties for its tablet formulation development. Three cocrystals of Cel with tartaric acid (Ta), cinnamic acid (Ca), and salicylamide (Sal) were prepared to improve these properties of Cel and characterized by PXRD, DSC and FTIR. The cocrystals underwent comprehensive in vitro characterization, encompassing equilibrium solubility, dissolution, and tabletability profiling, followed by in vivo pharmacokinetic evaluation to assess bioavailability and pharmacodynamic performance. The results demonstrated significant improvements in pharmaceutical properties by preparing the cocrystals of Cel. The equilibrium solubility of the Cel-Ca cocrystal was 3.4 times of that of Cel, and the maximum dissolution of the Cel-Sal cocrystal was about 2.7 times of that of Cel. The tensile strengths of the cocrystals were greater than the critical tensile strength of 1.7 MPa for the formation of tablets, and the three cocrystals could be used for direct tabletting. In vivo pharmacokinetic studies showed that the cocrystals shortened the peak concentration time of oral absorption of Cel and significantly enhanced the relative bioavailability.