Crystal structure and habit of dirithromycin acetone solvate: A combined experimental and simulative study

• The single crystal of DIR acetone solvate was grown from acetone solution using a slow evaporation method.
• The molecular dynamics simulation method was applied to study the solvent effect.
• The relative growth rates of the main crystal habit faces were analyzed by visualizing their structures and calculating the energy values.
• The solvate crystal habit was predicted by a modified AE model and agreed well with the observed experimental morphology, which offered a reliable crystal habit prediction method.

Dirithromycin (DIR) was crystallized from acetone solvent in the form of an acetone solvate. Its crystal structure belongs to monoclinic, space group P21, with the unit cell parameters a=14.688(3) Å, b=11.6120(12) Å, c=14.9129(12) Å, β=94.794(10)°, and Z=2. Results of X-ray diffraction (XRD) and thermogravimetry–differential scanning calorimetry (TG–DSC) indicated that the solvent molecules could enter the crystal lattice and thus the solvate is formed. The molecular dynamics (MD) simulation method was applied to study the solvent effect. It revealed that the relative growth rates of the main crystal habit faces changed a lot, which made the most morphologically important habit face shift from (001) face to (100) face due to polar groups or atoms exposure and hence a large solvent interaction. The prism habit predicted by a modified attachment energy (AE) model agreed well with the observed experimental morphology grown from the acetone solution. This prediction method may help for a solvent selection to improve the morphology in the drug crystallization process.