Testing the flow-through capillary for the study of re-solvation processes in pharmaceutical compounds

Rohlíček, Ján; Zvoníček, Vít; Skořepová, Eliška; Šoóš, Miroslav

doi:10.1017/s0885715620000354

Cited by 2 publications

(4 citation statements)

References 20 publications

(24 reference statements)

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“…Solvate Molecular and Crystal Analysis. The IBR− FB solvate 16 was identified as channel-type where considerably smaller FB molecules, compared to the IBR molecules, occupy 20.1% of the unit cell volume. Further crystallographic details can be found in the work of Rohli ́cěk et al 16 or in Figure S1.…”

Section: Modeling Methodsmentioning

confidence: 99%

“…The IBR− FB solvate 16 was identified as channel-type where considerably smaller FB molecules, compared to the IBR molecules, occupy 20.1% of the unit cell volume. Further crystallographic details can be found in the work of Rohli ́cěk et al 16 or in Figure S1. Apart from the channels formed by FB, which lie along the bcrystallographic axis (see Figure S2), we can also observe that the channels are partially blocked by the IBR phenyl rings, which point almost perpendicular to the channels causing a concave shape to the channels instead of being simply straight.…”

Section: Modeling Methodsmentioning

confidence: 99%

“…Simulations Details. The structure of the unit cell of IBR−FB 16 used in this work is the cornerstone and the starting point for our MD simulations. The parametrization of FB and IBR molecules followed the recommended protocol.…”

Section: Nanoscale Modelingmentioning

confidence: 99%

“…11−13 Our group has performed an extensive solid form screening and has described the crystal structures of several IBR polymorphs and solvates, 14,15 including the fluorobenzene solvate (IBR−FB). 16 Here, we present a methodology that we developed to investigate the desolvation of IBR−FB solvate. First, we performed in situ PXRD measurements to monitor the thermal desolvation of IBR−FB.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Solvent–Drug Interactions on the Desolvation of a Pharmaceutical Solvate

et al. 2022

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In drug manufacturing, solvent-based methods are used for the crystallization of active pharmaceutical ingredients (APIs). Often, the solvent interacts with the API resulting in the formation of a new solid compound, the solvate. When desolvation occurs upon heating, it might result in the formation of new solid forms with significantly different physicochemical properties. Therefore, in this work, we study the desolvation kinetics by combining in situ powder X-ray diffraction (PXRD), all-atom molecular dynamics (MD) simulations, and macroscopic solid-state reaction kinetics modeling. The fluorobenzene (FB) solvate of Bruton’s tyrosine kinase inhibitor Ibrutinib (IBR) was used as a model system. While the macroscopic solid-state modeling provides information about the desolvation kinetics, the MD simulations were used to trace individual FB molecules inside the crystal lattice. The activation energy of confined solvent diffusion, obtained by MD simulations, agrees well with results of the macroscopic solid-state reaction kinetics modeling. In addition, MD simulations provided detailed information about the IBR–FB interactions at the nanoscale. The mechanism revealed is that the solvent molecules diffusion, controlled by distinct open-close gating conformational changes of the drug, triggers the desolvation throughout the crystal lattice.

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Section: Modeling Methodsmentioning

confidence: 99%

Section: Modeling Methodsmentioning

confidence: 99%

Section: Nanoscale Modelingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Solvent–Drug Interactions on the Desolvation of a Pharmaceutical Solvate

et al. 2022

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Formation of ibrutinib solvates: so similar, yet so different

Jirát

Rohlíček

Kaminský

et al. 2023

Int Union Crystallogr J

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The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real time by X-ray powder diffraction in a glass capillary. Crystal structures of chlorobenzene, bromobenzene and iodobenzene solvates are isostructural, whereas the structure of fluorobenzene solvate is different. Four different mechanisms for transformation were discovered despite the similarity in the chemical nature of the solvents and crystal structures of the solvates formed. These mechanisms include direct transformations and transformations with either a crystalline or an amorphous intermediate phase. The binding preference of each solvate in the crystal structure of the solvates was examined in competitive slurry experiments and further confirmed by interaction strength calculations. Overall, the presented system and online X-ray powder diffraction measurement provide unique insights into the formation of solvates.

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Testing the flow-through capillary for the study of re-solvation processes in pharmaceutical compounds

Cited by 2 publications

References 20 publications

Impact of Solvent–Drug Interactions on the Desolvation of a Pharmaceutical Solvate

Impact of Solvent–Drug Interactions on the Desolvation of a Pharmaceutical Solvate

Formation of ibrutinib solvates: so similar, yet so different

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