Crystallographic tomography and molecular modelling of structured organic polycrystalline powders

Gajjar, Parmesh; Nguyen, Tung; Sun, Jun; Styliari, Ioanna Danai; Bale, Hrishikesh; McDonald, S.A.; Burnett, Timothy L.; Tordoff, Benjamin; Lauridsen, E.M.; Hammond, R. B.; Murnane, Darragh; Withers, Philip J.

doi:10.1039/d0ce01712d

Cited by 10 publications

(8 citation statements)

References 66 publications

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“…The rigid-body intermolecular interaction energies for the habit surfaces of LGA interacting with LGA (solute phase) and H 2 O (solvent phase) probe molecules were predicted using the Systematic Search method. − ,, The interaction energies were calculated using an atom–atom summation method between the probe molecules and the molecules in the slab of the unrelaxed crystal surface. The probe molecules were moved to various grid points in 0.2 Å steps, covering the crystal surface, and at each grid position the probe molecules were rotated through three Euler angles in 30° steps to cover the rotational degrees of freedom of the molecule close to the surface.…”

Section: Methodsmentioning

confidence: 99%

A Digital Mechanistic Workflow for Predicting Solvent-Mediated Crystal Morphology: The α and β Forms of l-Glutamic Acid

Turner

Dawson

Edwards

et al. 2022

Crystal Growth & Design

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The solvent-mediated crystal morphologies of the α and β polymorphic forms of L-glutamic acid are presented. This work applies a digital mechanistically based workflow that encompasses calculation of the crystal lattice energy and its constituent intermolecular synthons, their interaction energies, and their key role in understanding and predicting crystal morphology as well as assessing the surface chemistry, topology, and solvent binding on crystal habit growth surfaces. Through a comparison between the contrasting morphologies of the conformational polymorphs of L-glutamic acid, this approach highlights how the interfacial chemistry of organic crystalline materials and their inherent anisotropic interactions with their solvation environments direct their crystal habit with potential impact on their further downstream processing behavior.

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Section: Methodsmentioning

confidence: 99%

A Digital Mechanistic Workflow for Predicting Solvent-Mediated Crystal Morphology: The α and β Forms of l-Glutamic Acid

Turner

Dawson

Edwards

et al. 2022

Crystal Growth & Design

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“…Several studies have shown the usefulness of thermodynamics for understanding the formation process of chemical species [30] such as ZnO [16,31] in certain specific conditions. Chemical stability diagrams derived from chemical data also have also informed stability predictions of reaction products in simple and complex systems, such as the formation of zinc corrosion products in an aqueous medium [32,33] .…”

Section: Resultsmentioning

confidence: 99%

Theoretical and Experimental Approach to the Production of ZnO Nanoparticles by Controlled Precipitation Method in Methanol

Suárez

León-Molina

2022

ChemistrySelect

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Several works have demonstrated the utility of thermodynamics for understanding the formation process of ZnO in a specific ambient. In this work, equilibrium relations, mass balances and charge balances were used to derive chemical stability and predominance diagrams that allow relating the experimental observations of the synthesis of zinc oxide in methanol by the precipitation method to the expected product composition. The proposed equilibrium model considers the formation of zinc complexes with acetate (OAc−) and hydroxide (OH−) ions. Zinc oxide was also synthesized in similar conditions as those employed for calculations. The reaction monitoring was carried out by measuring pH and it was compared with the pH estimated using the model. Structural characterization of the product by X ray diffraction and scanning electron microscopy was performed. The proposed model predicts the formation of zinc oxide as the only species in the solid state, which agrees with the experimental results.

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“…In contrast to the widely recognized mechanism of agglomeration through particle collisions, hexamine exhibits an interesting agglomeration mechanism involving nucleation, typically referred to as “primary” agglomeration. − Dendritic growth following from nucleation on the corners of hexamine’s morphology leads to clusters of around 6–7 crystals, which incorporate solvent inclusions into the structure upon further crystal growth. Although this mechanism has been thoroughly understood through the molecular modeling work by Nguyen et al, the agglomeration rate has not yet been quantified sufficiently for application in a PBM.…”

Section: Materials and Methodologymentioning

confidence: 99%

Development of a Digital Twin for the Prediction and Control of Supersaturation during Batch Cooling Crystallization

Leeming,

Mahmud,

Roberts

et al. 2023

Ind. Eng. Chem. Res.

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Fine chemicals produced via batch crystallization with properties dependent on the crystal size distribution require precise control of supersaturation, which drives the evolution of crystal size over time. Model predictive control (MPC) of supersaturation using a mechanistic model to represent the behavior of a crystallization process requires less experimental time and resources compared with fully empirical model-based control methods. Experimental characterization of the hexamine− ethanol crystallization system was performed in order to collect the parameters required to build a one-dimensional (1D) population balance model (PBM) in gPROMS FormulatedProducts software (Siemens-PSE Ltd.). Analysis of the metastable zone width (MSZW) and a series of seeded batch cooling crystallizations informed the suitable process conditions selected for supersaturation control experiments. The gPROMS model was integrated with the control software PharmaMV (Perceptive Engineering Ltd.) to create a digital twin of the crystallizer. Simulated batch crystallizations were used to train two statistical MPC blocks, allowing for in silico supersaturation control simulations to develop an effective control strategy. In the supersaturation set-point range of 0.012− 0.036, the digital twin displayed excellent performance that would require minimal controller tuning to steady out any instabilities. The MPC strategy was implemented on a physical 500 mL crystallizer, with the simulated solution concentration replaced by in situ measurements from calibrated attenuated total reflection−Fourier transform infrared (ATR-FTIR) spectroscopy. Physical supersaturation control performance was slightly more unstable than the in silico tests, which is consistent with expected disturbances to the heat transfer, which were not specifically modeled in simulations. Overall, the level of supersaturation control in a real crystallizer was found to be accurate and precise enough to consider future adaptations to the MPC strategy for more advanced control objectives, such as the crystal size.

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Crystallographic tomography and molecular modelling of structured organic polycrystalline powders

Abstract: A fundamental understanding of the behaviour of polycrystalline materials, including pharmaceuticals, is vital for control of their physicochemical and crystalline properties, which in turn has the potential to improve drug...

Cited by 10 publications

References 66 publications

A Digital Mechanistic Workflow for Predicting Solvent-Mediated Crystal Morphology: The α and β Forms of l-Glutamic Acid

A Digital Mechanistic Workflow for Predicting Solvent-Mediated Crystal Morphology: The α and β Forms of l-Glutamic Acid

Theoretical and Experimental Approach to the Production of ZnO Nanoparticles by Controlled Precipitation Method in Methanol

Development of a Digital Twin for the Prediction and Control of Supersaturation during Batch Cooling Crystallization

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