Dynamic cross-flow filtration: enhanced continuous small-scale solid-liquid separation

A key enabler for the future success of continuous manufacturing in pharmaceutical and fine chemical production processes is the control of product quality. Since approx. 90% of all small molecular active pharmaceutical ingredients produced involve a crystallization step, a holistic view on its process chain is crucial in order to ensure a defined particle size distribution, high purity, and specific polymorphic form. Different concepts for small-scale continuous crystallization are available, improving the product qualities in comparison to batch. Continuous solid–liquid separations, on the other hand, are rather scarce. Therefore, we designed and characterized an innovative continuous vacuum screw filter (CVSF) for solid–liquid separation, washing, and drying of suspensions in a small scale (up to 10 g of solid per minute). This contribution shows the general working principle of the CVSF as well as a systematic investigation of varying operating parameters on the particle size distribution (PSD), residual moisture, and residence time distribution of the solid phase. As a model system, l-alanine/water is used. The results show that the PSD can be entirely maintained while ensuring a narrow residence time distribution of the solid phase with axial dispersion numbers between 18.7 and 76.2. The residual moisture is for all experiments in a good range of 20–25%. Furthermore, it could be shown that the operability is possible over 8 h. Summarizing, the modular setup of the CVSF offers a maximized flexibility and thus rapid adaptability to changing market demands and product requirements.

Section: Introductionmentioning

confidence: 99%

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid–Liquid Separation of Suspensions

Steenweg

Seifert

Schembecker

et al. 2021

“…Moreover, they may be subjected to thermal degradation or have an agglomeration or attrition tendency. To address these issues, a technique of drying at low temperatures while forcing gentle internal powder movement may be applied. − As thermal drying is energy-intensive, moisture is removed mechanically as much as possible, typically via filtration. − In this context, a technology that allows a continuous drying of slurries or powders with a high moisture content after filtration could be beneficial. Reducing the residence time in comparison to batch processing can help minimize the risk of thermal degradation .…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Novel Drying Technology for Continuous Processing of Cohesive Materials: An Ibuprofen Case Study

Zettl

Aigner

Mannschott

et al. 2021

Self Cite

This work addresses the influence of several process parameters on the performance of a novel drying device (patent NL2020740B1). In the new dryer, the processed substance is conveyed through the grooves of a large rotor via an interlocking screw design. A gentle, forced flow is created, preventing agglomeration and attrition and enabling a new technology of continuous drying for poorly flowing substances, which are often applied in the pharmaceutical industry. Drying test runs are performed using waterwetted ibuprofen, a nonsteroidal anti-inflammatory drug with poor material flow properties. The substances were tested according to their size, shape, and flow properties prior to the test runs. The process parameters in question were the temperature, mass flow, air flow, rotational speed, and initial moisture. Additionally, test runs to estimate the drying mechanism and the long-term process behavior, as well as reprocessing tests of the substance ibuprofen, were executed. It was shown that the dryer's performance for cohesive materials was optimal (continuous process times of up to 10 h were possible with evaporation rates up to 688 g/h). The process was robust, with a few drawbacks related to materials that are prone to tribocharging.

“…Cross flow filtration is a well-known continuous filtration technique, mainly utilized during the processing of biological products to concentrate slurries. 164,165 166,167 and a rotary drum filter. 168,169 Researchers at MIT designed, built, and tested the prototype of a small-scale continuous pharmaceutical filtration instrument using linear motion.…”

Section: Recent Progress In Continuous Pharmaceutical Technologiesmentioning

confidence: 99%

“…Cross flow filtration is a well-known continuous filtration technique, mainly utilized during the processing of biological products to concentrate slurries. , Gursch et al. and Kossik et al reported studies related to this technique for API suspensions with a membrane-based device , and a rotary drum filter. , Researchers at MIT designed, built, and tested the prototype of a small-scale continuous pharmaceutical filtration instrument using linear motion . Pfizer developed a semicontinuous filter-drier with a 3-way valve, which filtered small amounts of slurry (15–30 mL) every cycle, yielding a kg per a day productivity .…”

Section: Recent Progress In Continuous Pharmaceutical Technologiesmentioning

confidence: 99%

Integrated Continuous Pharmaceutical Technologies—A Review

Domokos

Nagy

Szilágyi

et al. 2021

Innovation in the pharmaceutical industry has been limited for a long time to the research and development of new active compounds; meanwhile, the structure of the production, dominated by batchwise technologies, has not changed to date. As has already been demonstrated in several other industrial sectors, continuous manufacturing (CM) has many advantages over batch processes. Faster, cheaper, and more flexible production can be developed with a significantly higher level of quality assurance. In the recent years the main regulatory agencies recognized the need for a change in drug production and started to promote continuous technologies and encourage pharmaceutical companies to develop and adapt such processes. As a result, by today extensive research was conducted in the various fields of pharmaceutical technologies from drug substance to drug product manufacturing. Many publications deal with synthetic steps carried out in flow reactors and crystallizations implemented in a continuous manner, and on the formulation side continuous filtration, drying, granulation, and blending have all been studied to a lesser or greater extent. Moreover, besides the modification of these traditional processes to continuous operation, novel, intrinsically continuous technologies are being studied as well. In order to entirely exploit the advantages of CM, the mainly separately developed processes need to be integrated to form end-to-end systems from the raw materials to the final dosage forms. However, even the integration of two technological steps is a challenging task. The development of end-to-end systems requires deep process understanding and a holistic approach toward process development and optimization. The aim of this work is to give insight into the state-of-the-art and new directions in integrated continuous pharmaceutical technologies by critically reviewing the recent literature of the broad field.