Abstract:

Celecoxib (Cel), categorized as a Biopharmaceutics Classification System (BCS) Class II compound, exhibits extremely limited aqueous solubility together with inadequate powder mechanical performance, thereby posing substantial challenges for conventional tablet formulation. To address these limitations, three eutectic mixtures (EMs) of Cel were systematically developed using p-aminobenzoic acid (Paba), pyridinecarboxamid (Pca), and isonicotinamide (Isa) as coformers. The resulting systems were thoroughly characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). A comprehensive physicochemical evaluation was subsequently conducted, including the construction of binary phase diagrams as well as in vitro assessments encompassing equilibrium solubility, dissolution behavior, and tabletability profiling. The formation of eutectic systems markedly enhanced the pharmaceutical performance of Cel across multiple dimensions. Notably, the equilibrium solubility of the Cel-Isa eutectic increased to approximately 1.7-fold relative to pristine Cel, while the Cel-Paba system exhibited a nearly twofold enhancement in maximum dissolution. In addition, all eutectic formulations demonstrated tensile strengths exceeding the critical threshold of 1.7 MPa required for robust tablet formation, indicating substantially improved compactibility. Collectively, these findings highlighted that all three EMs possessed suitable mechanical integrity for direct compression, thereby offering a promising and practical strategy for improving both the biopharmaceutical and manufacturability attributes of Cel.

Key words: Celecoxib, Eutectic mixture, Tabletability, Solubility