Synthesis of Celecoxib-Eutectic Mixture Particles via Supercritical CO 2 Process and Celecoxib Immediate Release Tablet Formulation by Quality by Design Approach.

Hong, Seung-Hyeon; Dinh, Linh; Abuzar, Sharif Md; Lee, Eun Seok; Hwang, Sung-Joo

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). Purpose: 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 CO2 techniques and new tablet formulations were purposed. Methods: 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. Results: 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.

CELECOXIB; CARBON dioxide; SPRAY drying; SUPERCRITICAL fluids; X-ray powder diffraction; DRUG solubility; SUPERCRITICAL fluid chromatography; NANOCARRIERS

Pharmaceutics, 2022, Vol 14, Issue 8, p1549

1999-4923

Academic Journal

10.3390/pharmaceutics14081549