Enantiotropically related albendazole polymorphs.
In the present study we report the solid-state properties of albendazole (ABZ) re-crystallized from different solvents for comparison with the commercially available form. Crystalline phases were characterized as to thermal behavior, X-ray diffractometry, both on powder and single crystal, and solubility in methanol or 0.1 N HCl. The relevant thermodynamic parameters were calculated from solubility measurements at different temperatures. The re-crystallization of ABZ both from methanol and N,N-dimethylformamide afforded a new stable polymorph form (Form II) enantiotropically related to the commercially available ABZ (Form I), the latter being the metastable form at ambient temperature. Both forms proved to be physically quite stable, likely due to a high-energy barrier for the activation of the interconversion. ABZ in the solid state represents a rather complex system in which the molecular structural differences that could be associated with the polymorphism are of at least four possible types, or combinations of these: (a) tautomeric; (b) different conformations of either or both of the side-chains attached to the bicyclic ring system; (c) the occurrence of molecular disorder or its absence; (d) no essential difference in molecular structure but different hydrogen bonding arrangements in the two polymorphs.
Pranzo
Marco B
MB
Department of Pharmacy, University of Parma, Viale G.P. Usberti 27/A, 43124 Parma, Italy.
Cruickshank
Dyanne
D
Coruzzi
Massimo
M
Caira
Mino R
MR
Bettini
Ruggero
R
D015766:Albendazole / Q000737:chemistry*; D000871:Anthelmintics / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D012995:Solubility; D013237:Stereoisomerism
D000871:Anthelmintics; D015766:Albendazole