Advances in Pharmaceutical Co-crystal Screening: Effective Co-crystal Screening through Structural Resemblance

Co-crystal screening was applied under the assumption
that two
molecules having relatively similar chemical structures are likely
to form co-crystals with identical coformers, in an attempt to improve
co-crystal screening efficiency. Piracetam and Levetiracetam were
used as model compounds. Both molecules are racetam compounds and
have a relatively similar molecular structure. Eleven co-crystals
of Piracetam have been described in the literature using ten different
acids. These ten acids were selected as potential coformer candidates
for the preparation of Levetiracetam co-crystals. Four co-crystals
of Levetiracetam were successfully identified by solvent drop and
neat grinding: Levetiracetam–d-tartaric acid 1:1 (LDTA),
Levetiracetam–R/S-mandelic
acid 1:1 (L­(RS)­MA), Levetiracetam–S-mandelic
acid 1:1 (LSMA), and Levetiracetam–2,4-dihyroxybenzoic acid
1:1 (L2,4DHBA). The overall success rate of 40% shows the usefulness
of the presented approach. Structural investigation shows the increased
success rate to most likely be due to the proficiency of two similar
molecules to share the same driving force for assembling multicomponent
systems with similar coformers.