Stereochemical Control of Cocrystal and Hybrid Salt–Cocrystal Formation in the Baclofen–Mandelic Acid System
(2025) Crystal Growth & Design — Vol. 25, n° 16, p. 6830-6836 (2025)
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- Authors
Boonpalit, Kajjana 
Shemchuk, Oleksii Flood, Adrian E.
- Abstract
- Chiral resolution by crystallization is a highly scalable and economically viable technique crucial for the pharmaceutical industry. While the use of multicomponent crystals, such as salts and cocrystals, has been extensively explored for separating racemates, precisely controlling the solid form selection in systems with multiple possible interactions remains a significant challenge. This study investigates the mechanochemical and crystallization products resulting from various enantiomeric combinations of the chiral active pharmaceutical ingredient baclofen and mandelic acid. We reveal that combining enantiopure mandelic acid with racemic baclofen leads to chiral resolution through the formation of diastereomeric cocrystals. Conversely, combining racemic mandelic acid with baclofen produces solid solution hybrid salt–cocrystals, highlighting the diverse outcomes of specific enantiomeric pairings. The stability of multicomponent formations was complementarily studied by employing density functional theory to calculate the lattice energy of each form. These findings uniquely showcase how stereochemistry fundamentally governs both solid form selection and specific chiral recognition pathways at the molecular level, providing crucial insights into the rational design of advanced chiral separation strategies.
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Citations
Songsermsawad, S., Boonpalit, K., Shemchuk, O., Robeyns, K., Leyssens, T., & Flood, A. E. (2025). Stereochemical Control of Cocrystal and Hybrid Salt–Cocrystal Formation in the Baclofen–Mandelic Acid System. Crystal Growth & Design, 25(16), 6830-6836. https://doi.org/10.1021/acs.cgd.5c00779 (Original work published 2025)