Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights.

Transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and may quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides, and other APIs. By using different experimental techniques (broadband dielectric spectroscopy, differential scanning calorimetry, X-ray diffraction) we compare the effect of adding the large molecular weight polymer—polyvinylpyrrolidone (PVP K30)—and the small molecular weight excipient—octaacetylmaltose (acMAL)—on molecular dynamics as well as the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL–PVP and CEL–acMAL. ...