Downscaling cake filtration—Correlations between compressibility of lysozyme crystal filter cakes and filter area

Cornehl, Bianca; Weinkötz, Daniel; Nirschl, Hermann

doi:10.1002/elsc.201200105

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…The investigation on the reaction of protein crystals to mechanical stress demonstrates the importance of a deep understanding of the solid‐liquid separation of crystalline materials .…”

Section: Finding the Right Separation Technologymentioning

confidence: 99%

Preparative Protein Crystallization

2019

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Preparative protein crystallization can possibly replace one or more chromatographic steps in downstream processing. The development of such crystallization processes is demanding: first, promising principal crystallization conditions must be identified; second, details about the process must be defined; and third, the crystals have to be separated from the mother liquor without putting harm of their crystalline integrity. State‐of‐the‐art about these three steps is developing fast by (i) employing new screening methods which are based on fundamental understanding of the interaction of the protein molecules, (ii) application of existing concepts of technical bulk crystallization of small molecules to preparative protein crystallization, and (iii) making available specific gentle separation machinery.

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“…The investigation on the reaction of protein crystals to mechanical stress demonstrates the importance of a deep understanding of the solid‐liquid separation of crystalline materials .…”

Section: Finding the Right Separation Technologymentioning

confidence: 99%

Preparative Protein Crystallization

2019

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“…Filtration methods are usually applied because they are cheap and rather gentle. However, protein crystals are forming compressible and compact filter cakes, leading to bad filtration and washing properties [3]. Consequently, it would be advantageous to inhibit filter cake building.…”

Section: Introductionmentioning

confidence: 99%

Mechanical Stress on Lysozyme Crystals during Dynamic Cross‐Flow Filtration

2013

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The influence of mechanical stress on the crystal size distribution of lysozyme crystal slurries in a dynamic cross-flow device is discussed. The reduction of crystal size may have an influence on mass and resistance of the fouling layer. A filter test device with a filter area of 130 cm 2 is used for thickening. After thickening, a model impurity, namely bovine serum albumin, is washed out of the suspension. A reduction of crystal size due to stirring and a reduced fouling layer with increasing stirrer speed is observed. Furthermore, a higher stirring speed increases the specific filtrate flux. In the presence of the impurity, more crystal aggregates than single isometric crystals are formed and, hence, the decrease of crystal size due to shear forces is more pronounced than without impurity.

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“…Cornehl et al . ( 17 , 18 ) investigated the breakage of lysozyme crystals after cake filtration using two different habits (needle-shaped and isometric) at an applied pressure between 0.25 and 1 barg. The isometric crystals mostly suffered from attrition and chipping of edges from the larger particles, whilst the needles were completely broken/crushed.…”

Section: Introductionmentioning

confidence: 99%

On the Breakage of High Aspect Ratio Crystals in Filter Beds under Continuous Percolation

et al. 2020

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Purpose This work details experimental observations on the effect of liquid flow percolating through packed beds of crystals to elucidate how the filtration pressure severely alters the size distribution and crystal shape. Pressure filtration is widely used in the pharmaceutical industry, and frequently results in undesired size distribution changes that hinder further processing. Methods The percolation methodology presented fixes fluid flow through a bed of crystals, resulting in a pressure over the bed. X-ray computed tomography (XCT) provided detailed observations of the bed structure. Detailed 2D particle size data was obtained using automated microscopy and was analysed using an in-house developed tool. Results Crystal breakage is observed when the applied pressure exceeds a critical pressure: 0.5–1 bar for ibuprofen, 1–2 bar for β-L glutamic acid (LGA) and 2–2.5 bar for para amino benzoic acid (PABA). X-ray computed tomography showed significant changes in bed density under the applied pressure. Size analysis and microscope observations showed two modes of breakage: (i) snapping of long crystals and (ii) shattering of crystals. Conclusion LGA and PABA have a similar breakage strength (50 MPa), ibuprofen is significantly weaker (9 MPa). Available breakage strength data may be correlated to the volumetric Gibbs free energy. Data from 12 and 35 mm bed diameters compares well to literature data in a 80 mm filter; the smaller, easy to operate percolation unit is a versatile tool to assess crystal breakage in filtration operations.

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Downscaling cake filtration—Correlations between compressibility of lysozyme crystal filter cakes and filter area

Cited by 6 publications

References 9 publications

Preparative Protein Crystallization

Preparative Protein Crystallization

Mechanical Stress on Lysozyme Crystals during Dynamic Cross‐Flow Filtration

On the Breakage of High Aspect Ratio Crystals in Filter Beds under Continuous Percolation

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