Abstract
PurposeThis 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.MethodsThe 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.ResultsCrystal 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.ConclusionLGA 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.
Highlights
Needle-shaped crystals with a high aspect ratio are common in pharmaceutical and fine chemicals processes [1,2] and their breakage during crystallisation has been widely investigated [3,4,5]
The para amino benzoic acid (PABA) crystals reorganise by rotating the major axis of the needles towards the horizontal plane, giving a layered appearance when percolated at inlet pressure of 4 bar (equal to ΔPb= 3.92 bar, 3.78 bar (LGA) and 3.22 bar (PABA))
The voidage as determined by X-ray computed tomography (XCT) (Fig. 4) confirms the compression of the bed; the voidage for L glutamic acid (LGA) decreases by 5% compared to the reference material, for PABA crystals voidage progressively decreases with increasing pressure
Summary
Needle-shaped crystals with a high aspect ratio are common in pharmaceutical and fine chemicals processes [1,2] and their breakage during crystallisation has been widely investigated [3,4,5]. Particle engineering involves regulating the super saturation, hydrodynamic conditions and/or addition of seed to impart control over the particle size distribution (PSD), purity and polymorphic form of the resultant crystal product. Downstream operations such as filtration, washing and drying relinquish some of the controlled benefits imparted by the crystallisation, thereby presenting an issue. Isolation of crystals from the slurry is commonly carried out in a single agitated filter dryer (e.g. Nutsche filter dryer), or by centrifugation followed by drying [6,7]. The PSD of the final product can, as industry observes, dramatically change post isolation [3,12,13]
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