Impurity removal during filtration and washing – a mechanistic modelling approach

Ottoboni, Sara and Mehta, Bhavik and Gramadnikova, Ekaterina and Brown, Cameron and Mitchell, Niall (2022) Impurity removal during filtration and washing – a mechanistic modelling approach. In: 13th World Filtration Congress, 2022-10-05 - 2022-10-09.

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The focus of the work reported here combines filtration and washing operations commonly used in active pharmaceutical ingredient (API) purification and isolation by combining predicted and experimental data generated during upstream crystallization process. In detail, this work focuses on the development of a mechanistic model-based workflow for the optimization of an integrated filtration and washing model, with a view to minimize impurities in the isolated cake. A Carman-Kozeny filtration model is integrated with a custom diffusion with an axial dispersion washing modelling approach. The custom washing model describes a washing process where the feed wet packed bed obtained by filtering a suspension to dryland is washed by diffusion-dispersion mechanisms. To effectively track impurities in the cake, the diffusion-dispersion wash model considers dissolution of the solid phase. The model was designed as a series of 10 continuous stirred-tank reactors (CSTR) where the approach used to mimic the dispersion washing mechanism modelled with the plug flow (PF) approach. The integrated modelling tool uses information on the product crystal suspension characteristics predicted using gPROMS FormulatedProducts to predict filtration time, filtrate flow rate, and the composition of the filter cake and filtrate generated during filtration. The washing of the wet filtered cake is then simulated to predict: washing efficiency and to generate washing curves, cake and filtrate composition, and residual cake moisture content and composition. Mefenamic acid and paracetamol were selected as representative test compounds. Three different crystallization solvents were used for mefenamic acid and for paracetamol case, with relative structurally-related impurities deriving from synthesis. As first stage of the optimization workflow, a model validation approach has been used to estimate cake properties (e.g. specific cake resistance, cake volume, cake composition after washing, washing curve). The data used for validation was generated via smallscale batch pressure filter experiments. Following on, the validated model was used to explore the design space and aid in the set-up of the optimization entity decisions. The optimization problem was then configured to reduce the impurity concentration in the final cake after washing. The findings from this were translated to a final model to simulate the optimal operating point.