Continuous Processing of Active Pharmaceutical Ingredients Suspensions via Dynamic Cross-Flow Filtration

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.

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

“…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.

“…Gursch et al. (2015 and 2016) , studied a small-scale cross-flow membrane filtration device that utilized a high rpm rotor to drive filtration. The authors found a material-specific linear relationship between the feed and permeate rate.…”

Section: Introductionmentioning

confidence: 99%

Development of Continuous Filtration in a Novel Continuous Filtration Carousel Integrated with Continuous Crystallization

Liu

Domokos

Coleman

et al. 2019

Pharmaceutical manufacturing has been largely carried out in batch mode, which has disadvantages such as batch-to-batch variations and difficult scale-up. As a result, the pharmaceutical industry is going through the paradigm shift to continuous manufacturing. Many unit operations have been studied for continuous operation; however, the bottleneck largely lies in drug substance isolation processes, such as crystallization and filtration. Herein a novel commercial continuous filtration unit, the continuous filtration carousel (CFC), coupled with an innovative continuous crystallization system, the oscillatory baffle reactor (OBR), was studied to construct a truly continuous drug substance separation step where supersaturated solution was continuously crystallized and filtered to produce solid products without a hold-up tank. Two compounds were studied to evaluate the CFC performance: paracetamol and benzoic acid. Standalone filtration experiments were performed first to examine the operating parameters of the CFC from which an optimal set of operating parameters was chosen for the integration of continuous filtration and crystallization. Successful integration of continuous crystallization and filtration of paracetamol and benzoic acid was demonstrated where dry uniform paracetamol crystals were obtained while benzoic acid products were high in moisture content. Implementing drying functionality in the filter chamber can improve its performance. In hopes to expedite the application of continuous filtration in the pharmaceutical industry, a risk consideration discussion is given to identify and organize potential risk factors associated with continuous filtration.