Single-crystal Drying: Development of a Continuous Drying Prototype to Optimize Particle Flow and Residence Time Distribution

Zettl, Manuel; Aigner, Isabella; Hauser, Craig A.; Mannschott, Thomas; Wel, Peter van der; Schröttner, Hartmuth; Khinast, Johannes; Krumme, Markus

doi:10.1007/s12247-021-09573-2

Cited by 3 publications

(11 citation statements)

References 25 publications

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“…A long-term experiment and refeeding test runs were performed to evaluate the long-term stability of the process and establish the effect of increasing residence time in the dryer. The mean residence time was found to be around 25 min for a similar test run; therefore, the assumed total residence time of each particle is estimated to be around 75 min, as the particles were processed three times in total. The goal was to obtain a product with a residual moisture below 1 wt % of water.…”

Section: Resultsmentioning

confidence: 97%

“…The evaporated water is the difference between the amount of liquids at the in- and outlet (2.9). The weight percentages are calculated via eq 10. …”

Section: Methodsmentioning

confidence: 99%

“…The material falls on top of the large rotor of the outlet rotary valve and the small conveying screw scraps the dried powder out of the pockets of the larger rotor. A detailed description of the design is provided by Zettl et al 7 and is shown in Figure 1. Basically, the dryer can be looked at as a kind of extruder (with larger than normal barrel clearance to provide an escape path for the evaporated gas) with asymmetric screw designs (one single thread, one multiple threads) and optimized heat transfer through the larger screw being internally heated, with additionally heated housing and filter to avoid condensation.…”

Section: Methodsmentioning

confidence: 99%

“…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%

“…With higher solubility of particles in the liquid phase, solid bridges are formed upon drying, making the agglomerates stronger. 28 In this study, a new contact-convective dryer prototype based on the findings of Zettl et al 7,29 is investigated, which is intended to dry under vacuum and could be used for organic solvents and in harsh chemical environments. In this paper, the working principle and the main influences on the process were analyzed.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Zettl

Aigner

Mannschott

et al. 2021

Org. Process Res. Dev.

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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.

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Section: Resultsmentioning

confidence: 97%

“…The evaporated water is the difference between the amount of liquids at the in- and outlet (2.9). The weight percentages are calculated via eq 10. …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Zettl

Aigner

Mannschott

et al. 2021

Org. Process Res. Dev.

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Process analytical technology in Downstream-Processing of Drug Substances– A review

Neugebauer,

Zettl,

Moser

et al. 2024

International Journal of Pharmaceutics

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Industrial-Scale Continuous Vacuum Drying of Active Pharmaceutical Ingredient Paste: Determination of the Process Window

Aigner

Zettl

Schroettner

et al. 2022

Org. Process Res. Dev.

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Many efforts have been made in recent years to adopt and implement continuous processing into the pharmaceutical production chain, driven by the desire to optimize the process efficacy and cost as well as the product quality. In the current challenging times, the need for fast adaptable processes to enlarge and facilitate the drug production on short notice is even more immanent than before. Suitable equipment for some unit operations is still missing. Drying is one of those and one of the most complex processes in the active pharmaceutical ingredient (API) manufacturing chain. Drying can influence the surface structure, particle size, as well as the morphology, in the worst case even causing degradation, especially in heat-sensitive substances. When producing APIs by proper design of the crystallization process to the desired target properties, it is key to have a drying process that can remove residual liquids without changing the particles. Practically, this means not changing particle size distribution by neither agglomeration nor particle attrition. In this work, the process window of a process, enabling full-scale continuous drying of a crystalline API after crystallization and washing, was investigated. An Ibuprofen paste containing water and ethanol as a liquid phase has been dried in a continuous vacuum dryer. The particles undergo no change during the process, and the needle-shaped particle form as well as the volume mean diameter of ∼80 μm was maintained until the end of the process for a large process window. Furthermore, it was shown that this continuous process can be run successfully in a semicontinuous mode, which enables implementing this new process into the existing batch operating manufacturing plants. The process time is much faster as for conventional batch drying technology, and the product volume can be scaled via run time or the throughput, therefore enabling a fast response to change in drug demand.

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Single-crystal Drying: Development of a Continuous Drying Prototype to Optimize Particle Flow and Residence Time Distribution

Cited by 3 publications

References 25 publications

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

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

Process analytical technology in Downstream-Processing of Drug Substances– A review

Industrial-Scale Continuous Vacuum Drying of Active Pharmaceutical Ingredient Paste: Determination of the Process Window

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