The Identification and Characterization of a New Carbapenem CS-023 Solvate Polymorph Achieved by the Appropriate Crystal Washing and Drying

The solvation process of crystals is a complex parameter, especially for pharmaceuticals where the reproducible production of a consistent product is paramount. The solvation of a novel carbapenem CS-023 crystals with an ethanol/water system was challenging to determine. The solvation data were widely dispersed when the ethanol/water-solvated crystals were washed with the crystallization solvent, requiring a suitable washing and drying method to be devised. To this end, the industry-standard washing and drying method were scrutinized, and a plausible drying mechanism was established. Firstly, an azeotropic solvent such as 96 wt% ethanol (although in this experiment, 96 v/v% ethanol was employed) was used as the washing solvent. Then, a new polymorph of CS-023, Form C (CS-023·EtOH·3H2O), was successfully identified. Form C was observed to produce steadily under a 40–70 v/v% ethanol solution. The relationship between Form C and Form A (CS-023·5/2EtOH·1/2H2O), which was previously obtained under 80 v/v% ethanol, was investigated next. Form A underwent solvent-mediated transformation to Form C under 40–70 v/v% ethanol.