Crystal structure of griseofulvin

On the Polymorphism of Griseofulvin: Identification of Two Additional Polymorphs

“…In particular, several solution crystallization studies using different solvents and different methods have revealed that, although the crystallization protocol has a strong influence on crystal habit, they have no influence on the crystalline structure of griseofulvin. 15,18,19 The same conclusion arises from the many papers investigating crystallization from the melt, which is always reported to produce form I. 13,14,16,17,20,21 The systematic development of two new polymorphic forms (II and III) in the DSC experiments reported in the present paper is thus puzzling.…”

“…However, the identification of polymorphism in griseofulvin is puzzling because this material is widely recognized as not demonstrating polymorphism. In particular, several solution crystallization studies using different solvents and different methods have revealed that, although the crystallization protocol has a strong influence on crystal habit, they have no influence on the crystalline structure of griseofulvin 15,18,19. The same conclusion arises from the many papers investigating crystallization from the melt, which is always reported to produce form I 13,14,16,17,20,21.…”

“…Figure 2 shows the RT PXRD patterns of forms I, II, and III of griseofulvin. The form I trace is from the initial commercial crystalline material, and shows well defined Bragg peaks corresponding to the tetragonal form ( P 4 1 ) reported in the literature 19. The form II sample was produced by DSC using the same thermal protocol as described for run 3 above: a melt was quenched at 0°C, annealed at 190°C during 600 min, cooled at RT, retrieved from the DSC pan, and placed in a Lindemann capillary for characterization.…”

“…However, despite the wide range of crystallization conditions used during the early polymorph screening stage of the pharmaceutical development process, new unexpected polymorphs are frequently discovered through subsequent chance investigations of drugs 12. Griseofulvin is an antifungal drug believed to exist in only one crystalline form 13–21. In this paper, we report the identification of two new polymorphic forms of this drug, which have escaped many previous investigations of this compound.…”

Comparative crystal structure determination of griseofulvin: Powder X-ray diffraction versus single-crystal X-ray diffraction

“…The results from the two methods correlate with each other very well. To further investigate the comparison between powder and single-crystal X-ray diffraction we chose griseofulvin [7], crystal structure of which was determined by Puttaraja et al [8] and Malmros et al [9] from single-crystal diffraction data, as the researching material. Because regular griseofulvin crystals can be easily obtained in conventional circumstance for single-crystal X-ray diffraction and it has a rigid molecular structure ( Figure 1) which can contribute to successful structure determination by powder X-ray diffraction.…”