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

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.