Polymorph Screening: Comparing a Semi-Automated Approach with a High Throughput Method

Polymorph screening studies of sulfathiazole, mefenamic acid, flufenamic acid, and ROY were carried out using a semi-automated apparatus. Cooling crystallization and slurry aging experiments were conducted with varying process conditions and a selection of 16 diverse solvents to Find as many polymorphic forms as possible. Results yielded four out of five polymorphs of sulfathiazole, both polymorphs and a solvate of mefenamic acid, four out of the seven stable forms of ROY, as well as the two most commonly encountered polymorphs and a solvate of flufenamic acid. The results obtained in this study were compared with a novel high throughput method based on patterned substrates of self-assembled monolayers.(17,32,38) It was shown that in the case of sulfathiazole and mefenamic acid the same number of polymorphs were obtained using the two approaches, In the case of ROY, the semi-automated approach was not able to produce three of the forms found using the patterned self-assembled monolayers (SAMs) method. These three forms were found in fewer than 1%. of approximately 10000 experiments performed using the high throughput approach and thus will be very difficult to rind in the 58 experiments performed using the semi-automated approach. Results of this study demonstrate that the simple semi-automated approach of similar to 60 experiments described in this work is suitable for early stage polymorph screening as it was able to reproduce effectively the diversity of polymorphs in model compounds.