Synthesis of Celecoxib-Eutectic Mixture Particles via Supercritical CO Process and Celecoxib Immediate Release Tablet Formulation by Quality by Design Approach.

Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO techniques and new tablet formulations were purposed. CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP (SAS institute) was applied to CEL EM immediate release tablet formulation development. CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.