Characterization of a New Solvatomorph of Drospirenone by Thermogravimetry–Mass Spectrometry Combined with Other Solid-State Analysis Methods

Drospirenone (DE) is a fourth-generation
progesterone that has
been widely used in oral contraceptives for women because of its safety
and few side effects in terms of pharmacological activity. A new solvatomorph
(crystal form C) of DE with dimethyl sulfoxide was identified and
characterized for the first time through a thermogravimetry–mass
spectrometry (TG–MS) coupling system. The thermodynamic property
of the new solvatomorph of DE was different from those of most pharmaceutical
solvatomorphs, and it was revealed via the skimmer-type interfaced
TG–MS system and differential scanning calorimetry. This new
solvatomorph and a polymorph of DE obtained without solvent (crystal
form A) were well characterized by X-ray crystallography and vibrational
spectroscopic analysis. Computational studies based on their single-crystal
structures, such as Hirshfeld surface analyses, were used to determine
the intermolecular interactions in the crystal network. The single-crystal
structure of crystal form C of DE was determined and reported for
the first time.