TY - JOUR
T1 - Piracetam and Oxiracetam Afford Molecular, Cocrystalline, and Ionic Cocrystalline Solid Solutions
AU - Spoletti, Enrico
AU - Wen, Ting
AU - Leng, Fucheng
AU - Boukioud, Nathan
AU - Lacey, Jason Carty
AU - Darwish, Shaza
AU - Shemchuk, Oleksii
AU - Robeyns, Koen
AU - Leyssens, Tom
AU - Lusi, Matteo
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society
PY - 2025/8/20
Y1 - 2025/8/20
N2 - 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–xSS, 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.
AB - 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–xSS, 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.
UR - https://www.scopus.com/pages/publications/105013891468
U2 - 10.1021/acs.cgd.5c00735
DO - 10.1021/acs.cgd.5c00735
M3 - Article
AN - SCOPUS:105013891468
SN - 1528-7483
VL - 25
SP - 6754
EP - 6763
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 16
ER -