Screening, Synthesis, and Characterization of a More Rapidly Dissolving Celecoxib Crystal Form

• Published in: ACS omega Vol. 9; no. 27; pp. 29710 - 29722
• Main Authors: O’Sullivan, Aaron, Spoletti, Enrico, Ross, Steven A., Lusi, Matteo, Douroumis, Dennis, Ryan, Kevin M., Padrela, Luis
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.07.2024
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c03188

The prevalence of poor solubility in active pharmaceutical ingredients (APIs) such as celecoxib (CEL) is a major bottleneck in the pharmaceutical industry, leading to a low concentration gradient, poor passive diffusion, and in vivo failure. This study presents the synthesis and characterization of a new cocrystal of the API CEL. CEL is a nonsteroidal anti-inflammatory drug used for the treatment of osteoarthritis and rheumatoid arthritis. Computational screening was completed for CEL against a large library of generally recognized as safe (GRAS) coformers, based on molecular complementarity and hydrogen bond propensity (HBP). The generated list of 17 coformers with a likelihood for cocrystallization with CEL were experimentally screened using four techniques: liquid-assisted grinding (LAG), solvent evaporation (SE), gas antisolvent crystallization (GAS), and supercritical enhanced atomization (SEA). One new crystalline form was isolated, employing the liquid coformer N-ethylacetamide (NEA). This novel form, celecoxib-di-N-ethylacetamide (CEL·2NEA), was characterized by a variety of different techniques. The crystal structure was determined through single-crystal X-ray diffraction. Both NEA molecules are evolved from the crystal structure at a desolvation temperature of approximately 65 °C. The CEL·2NEA cocrystal exhibited a dissolution rate, with more than a twofold improvement in comparison to as-received CEL after only 15 min.