Solvates of the antifungal drug griseofulvin: structural, thermochemical and conformational analysis.
Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the solvates were characterized by differential scanning calorimetry, thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The solvents that form the solvates are acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all the solvates lose the solvent molecules from the crystal lattice between 343 and 383 K, and that the melting point of the desolvated materials matched the melting point of the solvent-free GF (493 K). The conformation of the GF molecule in solvent-free form was found to be significantly different from the conformations found in the solvates. Solution stability studies revealed that the GF-acetonitrile solvate transforms to GF and that GF-nitroethane (1:1) solvate transforms to GF-nitroethane (2:1) solvate. On the other hand, GF-nitromethane and GF-nitroethane (2:1) solvates were found to be stable in solution. Our results highlight the importance of the co-crystallization technique in the pharmaceutical drug development; it not only expands the solid form diversity but also creates new avenues for unraveling novel solvates.
Crystallization and Particle Science, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833.
Srinivasulu
S
Aitipamula
Crystallization and Particle Science, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833.
Pui Shan
PS
Chow
Crystallization and Particle Science, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833.
Reginald B H
RB
Tan
D000097:Acetonitriles / Q000737:chemistry; D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D004980:Ethane / Q000031:analogs & derivatives / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry*; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009595:Nitroparaffins / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D013818:Thermogravimetry
D000097:Acetonitriles; D000935:Antifungal Agents; D009595:Nitroparaffins; D012996:Solutions; D012997:Solvents; D006118:Griseofulvin; C014705:nitroethane; D004980:Ethane; D008697:Methane; C008640:nitromethane; C032159:acetonitrile
conformational analysis; griseofulvin; solvates; thermal analysis