Baloxavir marboxil (BXM) is a new blockbuster FDA-approved anti-influenza virus agent. However, its poor solubility has limited its oral bioavailability. In this study, BXM was crystallized from several organic solvents, obtaining three polymorphs, and their dissolution behaviors were studied. Detailed crystallographic examination revealed that Form I is monoclinic, space group P21, with unit cell parameters a = 7.1159 (3) Å, b = 20.1967 (8) Å, c = 9.4878 (4) Å, β = 109.033 (1)°, V = 1289.02 (9) Å3, and Z = 2, and Form II is monoclinic, space group P21, with unit cell parameters a = 7.1002 (14) Å, b = 39.310 (7) Å, c = 9.7808 (18) Å, β = 110.966 (5)°, V = 2549.2 (8) Å3, and Z = 4. Form I has a rectangular three-dimensional energy frameworks net, while Form II has a two-dimensional net. On the other hand, Form II has a much larger percentage of its surface area of exposed hydrogen bond acceptors than Form I. These crystallographic features offered increased solubility and dissolution rate to Form II. The results of stability and solubility experiments suggest that Form II may be preferred in the solid form used for the industrial preparation of BXM medicinal products.

Dotinurad, a novel selective urate reabsorption inhibitor, was studied for preformulation beneficiation by supramolecular methods. Two polymorphic forms (form I, form II), a monohydrate, and four solvates were prepared and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermal analysis, which enabled the respective molecular conformation, intermolecular interactions, and packing arrangements to be determined. Combined with Hirshfeld surface analysis and energy networks, the stability and conformations of the above seven solid forms were studied by thermal analysis, crystal structure, and experimental results of solvent-mediated transitions and heat-treated transitions. Interestingly, form I and five solvates were transformed to form II under solvent suspension easily and quickly. The desolvation of DT solvates resulted in form II, which is mainly related to the hydrogen bonds between DT molecules and solvents.