Abstract:
Febuxostat exhibits unprecedented solid forms with a total of 40
polymorphs and pseudopolymorphs reported. Polymorphs differ in molecular
arrangement and conformation, intermolecular interactions, and various physicochemical properties, including mechanical properties. Febuxostat Form Q (FXT
Q) and Form H1 (FXT H1) were investigated for crystal structure, nanomechanical
parameters, and bulk deformation behavior. FXT Q showed greater compressibility,
densification, and plastic deformation as compared to FXT H1 at a given
compaction pressure. Lower mechanical hardness of FXT Q (0.214 GPa) as
compared to FXT H1 (0.310 GPa) was found to be consistent with greater
compressibility and lower mean yield pressure (38 MPa) of FXT Q. Superior
compaction behavior of FXT Q was attributed to the presence of active slip systems
in crystals which offered greater plastic deformation. By virtue of greater
compressibility and densification, FXT Q showed higher tabletability over FXT
H1. Significant correlation was found with anticipation that the preferred
orientation of molecular planes into a crystal lattice translated nanomechanical parameters to a bulk compaction process.
Moreover, prediction of compactibility of materials based on true density or molecular packing should be carefully evaluated, as
slip-planes may cause deviation in the structure−property relationship. This study supported how molecular level crystal
structure confers a bridge between particle level nanomechanical parameters and bulk level deformation behavior.
