Effect of Air Injection on Nucleation Rates: An Approach from Induction Time Statistics

From disruption of the supersaturated solution to improved mass transfer in the crystallizing suspension, the introduction of a moving gas phase in a crystallizer could lead to improved rates of nucleation and crystal growth. In this work, saturated air has been injected to batch crystallizers to study the effects on formation of the first crystal and subsequent turbidity buildup. To account for the typically large sample-to-sample variation, nucleation rates were evaluated for a large number of replicates using probability distributions of induction times. The slope and the intercept of the distributions were studied independently, allowing the simultaneous determination of the mean induction time and a certain detection delay related to the rate of crystal growth after formation of the first nucleus. When saturated air was injected in aqueous glycine solutions, the average detection delay was reduced from 69 to 13 min, and the mean induction time decreased from 128 to 36 min. The effect on aqueous solutions of l-arginine was less apparent, with a detection delay reduction from 15 to 3 min, and no significant changes on the rate of primary nucleation. These results demonstrate the potential of this technique for reduction in nucleation induction time and improved mass deposition rates in crystallization operations

Characterization of a Multistage Continuous MSMPR Crystallization Process assisted by Image Analysis of Elongated Crystals

This work demonstrates how quantitative image analysis can assist in the characterization of continuous crystallization processes and in the proper selection of mathematical models for the early assessment of crystal quality. An active pharmaceutical ingredient presenting an elongated crystal habit was crystallized using two stirred tank crystallizers in series. With image analysis of the crystallization magma, the sources of crystal breakage in the crystallization cascade were identified, and the impact on crystal habit was evaluated quantitatively. As it is expected for particles presenting high aspect ratios, crystal breakage preferentially occurs in the smallest plane, perpendicular to the largest dimension. This phenomenon is hardly avoidable in downstream production, but it can be accounted for with a design approach based on the real crystal dimensions. The kinetic rate equations for nucleation and crystal growth were determined based on crystal width, from which a model for the accurate prediction of this dimension was applied. The predicted crystal size distribution is consistent through a moderate degree of crystal breakage during downstream processing

Osmosis in a minimal model system

Osmosis plays a central role in the function of living and soft matter systems. While the thermodynamics of osmosis is well understood, the underlying microscopic dynamical mechanisms remain the subject of discussion. Unraveling these mechanisms is a crucial prerequisite for eventually understanding osmosis in non-equilibrium systems. Here, we investigate the microscopic basis of osmosis, in a system at equilibrium, using molecular dynamics simulations of a minimal model in which repulsive solute and solvent particles differ only in their interactions with an external potential. For this system, we can derive a simple virial-like relation for the osmotic pressure. Our simulations support an intuitive picture in which the solvent concentration gradient, at osmotic equilibrium, arises from the balance between an outward force, caused by the increased total density in the solution, and an inward diffusive flux caused by the decreased solvent density in the solution. While more complex effects may occur in other osmotic systems, they are not required for a description of the basic physics of osmosis in this minimal model.Comment: 10 pages, 8 figure

Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide using Flow Chemistry

© 2018 American Chemical Society. The kinetics of sequential addition of a distinct Grignard species onto a lactone is studied by flow chemistry. The experimental data are shown to be consistent with a kinetic model based on four reaction steps, reaction of ester to magnesium hemiacetal, rearrangement to ketone (forward and backward), and reaction of ketone to tertiary alcohol upon quenching. The experimental derived reaction mechanism is supported by ab initio molecular computations, and the predicted activation energy is in good agreement with the experimental observations. The Grignard reaction follows a substrate-independent, reductive [2 + 2] cycloaddition of the Meisenheimer/Casper type. Moreover, the rearrangement equilibrium between magnesium hemiacetal and ketone is characterized and found to be feasible. Monoaddition of the ester carbonyl group is demonstrated for fluorophenylmagnesium bromide but at reaction conditions at -40 °C with several hours of residence time. Working under cryogenic temperature conditions is essential to realizing monoaddition of the ester carbonyl group with Grignard reagents

LiSEQ – whole-genome sequencing of a cross-sectional survey of Listeria monocytogenes in ready-to-eat foods and human clinical cases in Europe

Funding information This work was funded by EFSA, contract number C/EFSA/BIOCONTAM/2014/01-CT 1 on “Closing gaps for performing a risk assessment on Listeria monocytogenes in ready-to-eat (RTE) foods: activity 3, the comparison of isolates from different compartments along the food chain, and from humans using whole genome sequencing (WGS) analysis’, EFSA-Q-2014-00 026. Acknowledgements A. P., T. D. and K. G. are affiliated to the National Institute for Health Research – Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at University of Liverpool in partnership with Public Health England, in collaboration with the University of East Anglia, the University of Oxford and the Quadram Institute. A. P., T. D. and K. G. are based at Public Health England. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.Peer reviewedPublisher PD