Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs

Drug combinations have been the hotspot of pharmaceutical industry, but promising applications are limited by unmet solubility and low bioavailability. In this work, novel cocrystals, consisting two antithrombotic drugs with poor bioavailability in vivo, namely, apixaban (Apx) quercetin (Que), were developed to discover a potential method improve internal absorption drug combination. Compared Apx, dissolution behavior Apx–Que (1:1) Apx–Que–2ACN (1:1:2) was enhanced significantly, while physical mixture chemicals failed exhibit advantages. The improvements could be explained fact that solid dispersion-like structure column-shaped cage Que accelerated access solvent inner layer Apx. fracture hydrogen bonds which joint adjacent chains, facilitated break-up structures. Besides, increased compared remained stable high temperature illumination conditions. Therefore, drug–drug cocrystal agents developed, exhibited greatly improved solubility, superior stability, indicating overcome shortages