Crystallization Process Design for Pharmaceutical Manufacturing

Crystallization is a key unit operation in the pharmaceutical industry. The control of crystallization processes can be challenging when undesirable phenomena such as particle attrition and breakage occur. This seminar describes the design of highly efficient and controlled processes for the crystallization of pharmaceuticals and amino acids, where crystal properties are especially important for the reliable operation of downstream processes and efficacy of drug products. Crystallization designs are described in which (1) undesirable phenomena do not occur and (2) the phenomena that do occur are carefully controlled. A crystallizer is described that employs micromixers designed to provide controlled nucleation to generate crystals that are highly uniform in size. The slurry flow is combined with an air flow and fed to a tube to induce a multiphase hydrodynamic instability that spontaneously generates well-mixed slugs where the crystals continue to grow. These slugs are well-mixed without having the mixing blades as in traditional crystallizer designs that induce undesirable particle attrition. Additional degrees of freedom for the control of crystal growth are created by spatially varying the temperature profile along the tube. An alternative design is described that replaces the micromixer with the application of focused ultrasonication. Experimental validation confirms that the proposed crystallizer designs reduce production time and equipment cost by orders of magnitude while suppressing secondary nucleation, attrition, and aggregation—dominant but undesired phenomena that worsen the ability to control the crystal properties

Exploiting the SARS-CoV-2 Spike Protein Components to Guide Molecular Level Entry of a BAG-1 Inhibitor in the Treatment of Breast and Lung Cancers

Chemoresistance of lung cancer cells is the primary reason as to why limitations occur with cancer treatments. A protein, known as BAG-1 is responsible for many cellular activities including cellular stress response, cell growth, and apoptosis (regulated cell death). When overexpressed, the protein has been linked to the anti-apoptotic behavior of cancer cells. BAG-1 can combine to heat shock proteins (HSPs), a family of helical molecular chaperones that are known to aid in the maturation of proteins, refolding, and degradation. This response plays a crucial role in the study of chemoresistance in cancer patients due to its detrimental nature. Prior, this combination was combated by using a synthesized poly-arginine linked peptide inhibitor alongside cell penetrating peptides (CPPs) through targeted binding domains. However, it has been found that the Spike protein of SARS-CoV-2 uses several small subdomains to efficiently bind to human epithelial cells at the nanomolar level. This study aims to focus on the binding complex of the BAG-1 and Spike proteins to form an anti-apoptotic inhibitor that can result in a potential specific binding mechanism for drug delivery of lung cancer treatments.https://scholarscompass.vcu.edu/reu/1007/thumbnail.jp

Association rules between the microstructure and physical mechanical properties of rock-mass under coupled effect of freeze-thaw cycles and large temperature difference

The mechanical properties of fractured rock mass are largely dependent on the fracture structure under the coupling of freeze-thaw cycles and large temperature difference. Based on the traditional macroscopic continuum theory, the thermal and mechanical model and the corresponding theories ignore the material internal structure characteristics, which add difficulty in describing the mesoscopic thermal and mechanical behavior of the fractured rock mass among different phases. In order to uncover the inherent relationship and laws among the internal crack development, structural change and the physical and mechanical properties of rock under strong cold and frost weathering in cold area, typical granite and sandstone in cold region were analyzed in laboratory tests. The SEM scanning technology was introduced to record the microstructural change of rock samples subject to freeze-thaw cycles and large temperature difference. Association rules between the microstructure and the physical mechanical properties of rock mass were analyzed. The results indicated that, with the increase of the cyclic number, the macroscopic physical and mechanical indexes and the microscopic fracture index of granite and sandstone continuously and gradually deteriorate. The width of original micro crack continues to expand and extend and new local micro cracks are generated and continue to expand. The fracture area and width of the rock increase and the strength of the rock is continuously damaged. In particular, the strength and elastic modulus of granite decrease by 20.2% and 33.36%, respectively; the strength and elastic modulus of sandstone decrease by 33.4% and 36.43%, respectively

In-Silico Conceptualisation of Continuous Millifluidic Separators for Magnetic Nanoparticles

Magnetic nanoparticles are researched intensively not only for biomedical applications, but also for industrial applications including wastewater treatment and catalytic processes. Although these particles have been shown to have interesting surface properties in their bare form, their magnetisation remains a key feature, as it allows for magnetic separation. This makes them a promising carrier for precious materials and enables recovery via magnetic fields that can be turned on and off on demand, rather than using complex (nano)filtration strategies. However, designing a magnetic separator is by no means trivial, as the magnetic field and its gradient, the separator dimensions, the particle properties (such as size and susceptibility), and the throughput must be coordinated. This is showcased here for a simple continuous electromagnetic separator design requiring no expensive materials or equipment and facilitating continuous operation. The continuous electromagnetic separator chosen was based on a current-carrying wire in the centre of a capillary, which generated a radially symmetric magnetic field that could be described using cylindrical coordinates. The electromagnetic separator design was tested in-silico using a Lagrangian particle-tracking model accounting for hydrodynamics, magnetophoresis, as well as particle diffusion. This computational approach enabled the determination of separation efficiencies for varying particle sizes, magnetic field strengths, separator geometries, and flow rates, which provided insights into the complex interplay between these design parameters. In addition, the model identified the separator design allowing for the highest separation efficiency and determined the retention potential in both single and multiple separators in series. The work demonstrated that throughputs of ~1/4 L/h could be achieved for 250–500 nm iron oxide nanoparticle solutions, using less than 10 separator units in series