# Integrated Filtration and Washing Modeling: Optimization of Impurity Rejection for Filtration and Washing of Active Pharmaceutical Ingredients

## TL;DR

This paper presents a digital tool to optimize filtration and washing processes in pharmaceutical manufacturing to reduce impurities in active ingredients.

## Contribution

The novel contribution is a mechanistic model combining filtration and washing to optimize impurity rejection in API isolation.

## Key findings

- A custom washing model simulates washing stages and species concentration evolution.
- The model was validated using mefenamic acid and paracetamol systems with various solvents and impurities.
- Optimized isolation conditions were simulated to reduce final cake impurity concentrations.

## Abstract

A digital design tool that can transfer material property
information
between unit operations to predict the product attributes in integrated
purification processes has been developed to facilitate end-to-end
integrated pharmaceutical manufacturing. This work aims to combine
filtration and washing operations frequently using active pharmaceutical
ingredient (API) isolation. This is achieved by coupling predicted
and experimental data produced during the upstream crystallization
process. To reduce impurities in the isolated cake, a mechanistic
model-based workflow was used to optimize an integrated filtration
and washing process model. The Carman–Kozeny filtration model
has been combined with a custom washing model that incorporates diffusion
and axial dispersion mechanisms. The developed model and approach
were applied to two systems, namely, mefenamic acid and paracetamol,
which are representative compounds, and various crystallization and
wash solvents and related impurities were used. The custom washing
model provides a detailed evolution of species concentration during
washing, simulating the washing curve with the three stages of the
wash curve: constant rate, intermediate stage, and diffusion stage.
A model validation approach was used to estimate cake properties (e.g.,
specific cake resistance, cake volume, cake composition after washing,
and washing curve). A global systems analysis was conducted by using
the calibrated model to explore the design space and aid in the setup
of the optimization decision variables. Qualitative optimization was
performed in order to reduce the concentration of impurities in the
final cake after washing. The findings of this work were translated
into a final model to simulate the optimal isolation conditions.