New Solid Forms of Griseofulvin: A Solvate and a Relict Polymorph Related to Reported Solvates

Mariana O Diniz; Enrico Spoletti; Peuli Ghosh; Matteo Lusi; Michael Svärd; Åke Rasmuson; Sarah P Hudson

doi:10.1021/acs.cgd.3c01011

New Solid Forms of Griseofulvin: A Solvate and a Relict Polymorph Related to Reported Solvates

Cryst Growth Des. 2023 Nov 15;23(12):8953-8961. doi: 10.1021/acs.cgd.3c01011. eCollection 2023 Dec 6.

Authors

Mariana O Diniz^{1

2}, Enrico Spoletti², Peuli Ghosh^{1

2}, Matteo Lusi², Michael Svärd³, Åke Rasmuson^{1

2

3}, Sarah P Hudson^{1

2}

Affiliations

¹ SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals, University of Limerick, Limerick V94 T9PX, Ireland.
² Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
³ Department of Chemical Engineering, KTH Royal Institute of Technology, Stockholm SE-100 44, Sweden.

Abstract

This work presents two new solid forms, a polymorph and a solvate, of the antifungal active pharmaceutical ingredient griseofulvin (GSF). The novel forms were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The new polymorphic form (GSF Form VI) was obtained upon drying at room temperature the GSF-acetonitrile solvate. GSF Form VI is a relict structure related to reported solvates of GSF. Thermal stability studies show that Form VI is metastable and monotropically related to the stable GSF Form I. The new GSF-n-butyl acetate solvate was obtained by crystallization from an n-butyl acetate solution. The stoichiometry of the n-butyl acetate solvate is 1:0.5. The solvate loses the solvent from the crystal lattice at a temperature between 363.15 and 374.15 K.