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Development of an automated continuous clarification bypass system to remove suspended particulate matter

Introduction

Continuous manufacturing processes are important for valuable products in many industry sectors, such as food, polymers, petrochemicals, fine chemicals, and pharmaceuticals. For the continuous manufacturing of pharmaceuticals, the prereaction material usually contains some extraneous suspended particulate matter (SPM) that prevents the final API from passing the appearance of solution test required by the European Pharmacopeia and needs to be filtered before entering the reaction vessel (i.e., clarification). Filtration is a separation process that removes solids or droplets from liquids or gases by adding a filter medium that is permeable to only the fluid phase being separated. The term “clarification” is usually used when solids or droplets do not exceed 1.0%, and the filtrate is the primary product. The solids or droplets can be deposited on the outer surface of the filter medium, known as surface filtration, as well as within the filter medium’s depth, known as depth filtration. Most filtration processes are a combination of surface filtration and depth filtration, due to the wide range of the particle size distribution of solids. Usually, an initial depth filtration is followed by surface filtration; this transition starts once the void spaces of the upstream layers of the filter medium are reduced to a certain extent. Subsequently, particles start to deposit on the surface, leading to the buildup of the cake. During surface filtration, particles do not pass through the filter medium but are collected on the surface. In this case, the particle size should be larger than the pore size; however, in certain cases slightly smaller particles can bridge across the surface pores, preventing their passage through the filter. Surface filtration is also known as cake filtration if the flow of particles is directed perpendicular to the filter medium surface. The disadvantage of this process is that the filter cake builds up over time, reducing the flow rate of the filtrate. One solution to this problem is to use cross-flow filtration. In this case, fluids flow parallel to the surface, and the deposited cake is later removed by ongoing fluid flow. During depth filtration, particles penetrate the structure of the filter medium, and are captured and retained. As particles accumulate in the interstices, the cross-sectional area of the filter medium is reduced, damaging porosity and impairing permeability. Flow through the filter decreases, and higher pressure is required to maintain the flow rate, according to Darcy’s Law. One solution is to remove, or partially remove, these solids with a solvent backwash. In the present study, an automated pilot-scale continuous clarification bypass system was developed to remove suspended particulate matter (SPM) from the prereaction material, allowing the final API (1−3 kg/h throughput) to pass the appearance of solution test required by the European Pharmacopeia. Compared to commercially available duty/ standby filters, the proposed clarification bypass system has the ability to self-clean and does not require detachment of the filter and manual cleaning. Effects of flow direction, ultrasonication, feed viscosity/temperature, filter elements material, filter size, pore size, and switching pressure on the filter performance were investigated, and the filtration mechanisms are discussed.

Abstract

An automated continuous clarification bypass system was developed to remove the suspended particulate matter (SPM) in the prereaction material. Compared to commercially available duty/standby filters, the proposed clarification bypass system is able to self-clean and does not require detachment of the filter and manual cleaning. In a stainless steel (SS) filter, the effects of flow direction, ultrasonication, and viscosity were investigated. The data showed that the filtration performance could not meet the requirement of high clarification efficiency because of the high switch frequency. The deposition of crystals on the SS filter medium, and not the SPM, was the primary cause of the pressure build-up. Experiments with PTFE filter elements with comparable pore size and surface area to the stainless-steel filter were performed, and improved filtration performance was observed. At the beginning of the SPM filtration process with the PTFE filter elements, three filtration mechanisms occurred. As the filtration cake formed on the filter element surface, straining gradually dominated the filtration process, while the effects of impingement and entanglement became negligible.

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