Superior solubility of anhydrous quercetin and polymer physical mixtures compared to amorphous solid dispersions

Quercetin (QUE) is a functional flavonoid molecule with low water solubility. The study of its amorphous solid dispersions (ASDs) is still insufficient. This work reveals that the solubility of the physical mixtures of anhydrous QUE and polymers (PVP or soluplus) is better than that of the ASDs of QUE and the corresponding polymers. Gel-like phase separation occurring during the QUE ASDs dissolution process (weak in ASDs with PVP and strong in ASDs with soluplus) reduces the driving force for QUE release, which makes research on the QUE ASDs insufficient, and can be avoided in the QUE physical mixtures with polymers. Combination of metastable polymorph and polymer is a feasible strategy for improving the solubility of poorly water-soluble molecules whose ASDs encounter the gel-like phase separation.