Piracetam and Oxiracetam Afford Molecular, Cocrystalline, and Ionic Cocrystalline Solid Solutions

Spoletti, Enrico;Wen, Ting;Leng, Fucheng;Boukioud, Nathan;Lusi, Matteo;et.al.
(2025) Crystal Growth & Design — Vol. 25, n° 16, p. 6754-6763 (2025)

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Authors
  • Spoletti, Enrico
    Author
  • Wen, TingUCLouvain
    Author
  • Leng, FuchengUCLouvain
    Author
  • Boukioud, Nathan
    Author
  • Shemchuk, Oleksiiorcid-logoUCLouvain
    Author
  • Robeyns, Koenorcid-logoUCLouvain
    Author
  • Leyssens, Tomorcid-logoUCLouvain
    Author
  • Lusi, Matteoorcid-logo
    Author
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Abstract
Solid solutions (SSs) are relatively underexplored crystalline forms that allow precise dosage of multidrug formulations. The cocrystallization of the nootropic drugs Piracetam (PIR) and Oxiracetam (OXI) suggests that these phases have a richer scope than once thought. Despite their different H-bond capabilities, multiple solid solutions were obtained following a crystal engineering approach. A combination of the pure compounds produced multiple forms of PIRxRS-OXI1–x SS, whose structure depends on the PIR/OXI ratio. Such structural diversity is controlled when enantiopure S-OXI is used in PIRxS-OXI1–x, or when both drugs are cocrystallized with either a molecular coformer (gallic acid, GA) or an inorganic salt (MgCl2) to produce cocrystalline (CC) and ionic cocrystalline (ICC) SS: PIRx·RS-OXI1–x·GA, PIRx·S-OXI1–x·GA, and PIRxR/S-OXI1–x·MgCl2·5H2O. Thermal and humidity stability of each form is discussed, as well as the solubility profile of the GA CCSS. Overall, a rich solid-form landscape has been demonstrated for the combined drugs that allows for designing and optimizing them into molecular, cocrystalline, and ionic cocrystalline solid solutions.
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Spoletti, E., Wen, T., Leng, F., Boukioud, N., Lacey, J. C., Darwish, S., Shemchuk, O., Robeyns, K., Leyssens, T., & Lusi, M. (2025). Piracetam and Oxiracetam Afford Molecular, Cocrystalline, and Ionic Cocrystalline Solid Solutions. Crystal Growth & Design, 25(16), 6754-6763. https://doi.org/10.1021/acs.cgd.5c00735 (Original work published 2025)