Surface Induced Phenytoin Polymorph. 1. Full Structure Solution by Combining Grazing Incidence X-ray Diffraction and...

Area of Science:

• Solid-state chemistry
• Crystallography
• Materials science

Background:

• Understanding molecular crystalline packing is crucial for thin-film material properties.
• Phenytoin (5,5-diphenylhydantoin) can form surface-induced polymorphs.
• Conventional structure solving fails for small crystals with limited data.

Purpose of the Study:

• To determine the full crystal structure of a surface-induced phenytoin polymorph (form II).
• To compare the solid-state behavior of form II with the bulk form (form I).
• To investigate the influence of packing differences on dissolution rates.

Main Methods:

• Grazing incidence X-ray diffraction (GIXRD) was used to obtain experimental data.
• Computational structure generation was combined with experimental results.
• Structure solution was achieved by integrating computational and experimental approaches.

Main Results:

• The monoclinic unit cell of the new surface-induced phenytoin polymorph (form II) was determined.
• Significant differences in the hydrogen-bonding network were observed between form II and form I.
• Form II exhibited faster dissolution compared to form I, likely due to packing variations.

Conclusions:

• A combined computational and experimental approach successfully solved the crystal structure of form II.
• Packing differences, particularly in hydrogen bonding, influence the dissolution properties of phenytoin polymorphs.
• This integrated method is applicable to other systems with limited experimental data for solid-state analysis.