(421e) The Effect of Particle Sedimentation on the Performance of Pressure Filters

text-align:center;line-height:115%">The Effect of Particle
Sedimentation on the Performance of Pressure Filters

text-align:center;line-height:115%"> 115%;font-family:" times new roman mso-ansi-language:en-us>Fragkopoulos, I.S.¹, Mitchell, N.A.²,
MacLeod, C.S.³, Mathew, S.⁴ and Muller, F.L.¹

text-align:center;line-height:115%;text-autospace:none"> normal">¹ normal"> Chemical
and Process Engineering, University of Leeds, Leeds LS2 9JT, UK

text-align:center;line-height:115%;text-autospace:none"> normal">² normal">Process Systems Enterprise (PSE) Ltd., London
W6 7HA, UK

text-align:center;line-height:115%;text-autospace:none"> normal">³ normal"> Pharmaceutical
Development, AstraZeneca, Macclesfield SK11 2NA, UK

text-align:center;line-height:115%;text-autospace:none"> normal">⁴ normal">Global Research and Development, Pfizer,
Sandwich CT13 9NJ, UK

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115%">Pressure cake
filtration is commonly used in the pharmaceutical industry for the separation
of solids from the crystallisation slurry. The pressure applied has a huge
impact on the particles within a cake and in turn affects the resistance of the
liquid flowing through the cake [1]. This can cause the cake to compress and
clog the filter medium, both of which slow down the filtration process.
Although pressure can be increased to maintain a sufficient rate of filtration,
this would cause the cake to further compress and/or lead to particle breakage.
The filtration performance cannot currently be predicted accurately. Process
scale-up is based on extensive experimentation, but scale-up surprises still
occur between drug discovery and manufacturing. 12.0pt;line-height:115%;font-family:" times new roman calibri>The main focus of this work was the development
of a detailed filtration mechanistic model that takes experimental data and
estimates filtration process parameters, so as to enable the prediction and
control of the pressure filter performance at scale. The pressure filtration scale-up
strategy that was followed in this study, is depicted in Figure 1.

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line-height:115%;font-family:" times new roman calibri>

line-height:115%;font-family:" times new roman calibri>Figure 1: Pressure filtration
scale-up workflow.

Lab-scale filtration
experiments were performed for the investigation of the effect of size and
shape of AZ and Pfizer materials on the filtration performance. An improved t/V
filtration analysis model [2], which considers the fraction of solids that are
already settled before filtering starts, was used in conjunction with the
lab-scale filtration curves for the estimation of filtration parameters such as
medium resistance, specific cake resistance and compressibility index of the
cake.

justify;line-height:115%"> font-family:" times new roman en-us>Conventional Ruth-equation based filtration models are currently capable
of describing only two extreme cases, where:

auto;text-align:justify;text-indent:-18.0pt;mso-list:l1 level1 lfo4">a)      There is no sedimentation prior to filtration and cake
builds-up while filtering, assuming a well-dispersed slurry (see Fig.2a).

margin-bottom:12.0pt;margin-left:39.0pt;mso-add-space:auto;text-align:justify;
text-indent:-18.0pt;mso-list:l1 level1 lfo4">b)      Complete sedimentation is followed by filtration - permeation
of liquid through a settled cake (see Fig.2b).

However, in reality
the cake is commonly partly formed when filtration is initiated and also the
slurry is not well-dispersed during the entire filtration duration (a layer of
clear liquid at the top of the slurry is formed due to particle settling, as in
Fig. 2c).

mso-no-proof:yes">

6.0pt;line-height:150%;color:#A6A6A6">

margin-left:0cm"> normal"> " times new roman>Figure 2: normal"> " times new roman> Schematic representation of slurry in systems with
(a) no crystal sedimentation prior to filtration, (b) entire crystal
sedimentation prior to filtration and (c) partial crystal sedimentation prior
to filtration.

For this reason, a
filtration-sedimentation lumped parameter model, currently being prototyped in
PSE’s gPROMS FormulatedProducts suite, was developed and used to show the effect
of sedimentation during filtration on the process performance. Predicted
filtration times at pilot-plant and manufacturing scales were found to increase
by more than 10% and 15% respectively (for d50s of 10µm), when taking into
account particle settling.

justify;line-height:115%"> font-family:" times new roman en-us>The support of the Advanced Manufacturing Supply Chain Initiative
through the funding of the ‘Advanced Digital Design of Pharmaceutical
Therapeutics’ (ADDoPT) project (Grant No. 14060) is gratefully acknowledged.

justify;line-height:115%"> font-family:" times new roman en-us>

justify;line-height:115%">Keywords: particle settling,
pressure filtration, parameter estimation, scale-up, digital design.

justify;line-height:115%"> font-family:" times new roman en-us>

justify;line-height:115%">References

mso-list:l6 level1 lfo7">1.     
Hamilton, P., D.
Littlejohn, A. Nordon, J. Sefcik, P. Slavin, J. Andrews and P. Dallin (2013).
Investigation of factors affecting isolation of needle-shaped particles in a
vacuum-agitated filter drier through non-invasive measurements by Raman
spectrometry. Chemical Engineering Science, 101, 878–885.

mso-list:l6 level1 lfo7">2.     
Fragkopoulos, I.S., A.
Shier, C.S. MacLeod and F.L. Muller (2019). Constant Pressure Filtration of
Pharmaceuticals: An Integrated Experimental and Modelling Study. Chemical
Engineering Science, to be submitted.