Solid-liquid equilibrium and thermodynamic analysis of elastically bendable crystal celecoxib in thirteen pure solvents based on experiments and molecular simulation

Abstract

Celecoxib, which is the first elastically bendable single-component pharmaceutical crystal and a new generation of nonsteroidal anti-inflammatory drugs (NSAID) was chosen to investigate its dissolution behavior in thirteen pure solvents by experiments (gravimetric method) and theoretical analysis (including molecular stacking pattern diagram, Hirshfeld surface (HS) analysis, radial distribution function (RDF), and interaction energy). It was found that ester solvents have a better advantage in terms of solubility than alcoholic solvents and acetonitrile, in which ethyl acetate exhibits the best dissolving capacity for celecoxib while isobutanol possesses the smallest solubility. Furthermore, the results of RDF analysis indicate that there is strong hydrogen bond interaction between CXB and measured solvents. The calculation results of interaction energy revealed ethyl acetate has the highest interaction energy with CXB, which is correlated to the best dissolution capacity for CXB. Finally, the measured solubility data were correlated with the modified Apelblat equation, van't Hoff equation, and λh model. All the values of ARD% are lower than 5, indicating that the correlated data are in good agreement with the experimental solubility. The solubility data can offer a productive guide to the practical application areas of elastically bendable single-component pharmaceutical crystal.