A dimensionless analysis of residence time distributions for continuous powder mixing

Tian, Geng; Lee, Sau L.; Yang, Xiaochuan; Hong, Moo Sun; Gu, Zongyu; Li, Shuaili; Fisher, Robert J.; O’Connor, Thomas

doi:10.1016/j.powtec.2017.04.007

Cited by 39 publications

(8 citation statements)

References 6 publications

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“…Moreover, presence of rotating equipment, which influences the ratio between the convective and diffusive transport phenomena, has an impact on the shape of the RTD. This trend is consistent with the literature (Engisch and Muzzio, 2015a;Fullard and Davies, 2017;Paredes et al, 2017;Tian et al, 2017;Van Snick et al, 2017bVanarase and Muzzio, 2011), Figure 9. Predicted response to a simulated tracer impulse at t=0s (10 to 20 wt% API) for (A) blender, (B) roller compactor, (C) tablet press.…”

Section: Linear Prediction Of the Residence Time Distributionsupporting

confidence: 93%

RTD-based material tracking in a fully-continuous dry granulation tableting line

Martinetz

Karttunen

Sacher

et al. 2018

International Journal of Pharmaceutics

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Continuous manufacturing (CM) offers quality and cost-effectiveness benefits over currently dominating batch processing. One challenge that needs to be addressed when implementing CM is traceability of materials through the process, which is needed for the batch/lot definition and control strategy. In this work the residence time distributions (RTD) of single unit operations (blender, roller compactor and tablet press) of a continuous dry granulation tableting line were captured with NIR based methods at selected mass flow rates to create training data. RTD models for continuous operated unit operations and the entire line were developed based on transfer functions. For semi-continuously operated bucket conveyor and pneumatic transport an assumption based the operation frequency was used. For validation of the parametrized process model, a pre-defined API step change and its propagation through the manufacturing line was computed and compared to multi-scale experimental runs conducted with the fully assembled continuous operated manufacturing line. This novel approach showed a very good prediction power at the selected mass flow rates for a complete continuous dry granulation line. Furthermore, it shows and proves the capabilities of process simulation as a tool to support development and control of pharmaceutical manufacturing processes.

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Section: Linear Prediction Of the Residence Time Distributionsupporting

confidence: 93%

RTD-based material tracking in a fully-continuous dry granulation tableting line

Martinetz

Karttunen

Sacher

et al. 2018

International Journal of Pharmaceutics

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“…1,2 A comprehensive study of the dynamics of continuous process and how it gets impacted by choice of process parameters, equipment design and blend material properties enables; (a) the understanding of the propagation of disturbances introduced from the feeder and their impact on the critical quality attributes (CQA) of drug product, (b) traceability of the material through the line and isolate off-specification drug product. 3 Process dynamics is often characterized by RTD, which is a probability distribution function that describes the time spent by solid particles inside a unit operation. It is a key aspect of the control strategy.…”

Section: Introductionmentioning

confidence: 99%

Continuous Mixing Technology: Characterization of a Vertical Mixer Using Residence Time Distribution

Lee

Kimber

Cogoni

et al. 2021

Journal of Pharmaceutical Sciences

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“…The RTD can be used to characterize axial mixing and track materials through the process. The propagation of upstream disturbances can be tracked through the process by convolution of the disturbance and RTD (9). RTDbased in-process controls (IPCs) for CM processes can potentially effectively mitigate the risk of upstream disturbances on product quality (10,11).…”

Section: Introductionmentioning

confidence: 99%

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

Tian

Koolivand

et al. 2021

AAPS PharmSciTech

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Continuous manufacturing (CM) is an emerging technology which can improve pharmaceutical manufacturing and reduce drug product quality issues. One challenge that needs to be addressed when adopting CM technology is material traceability through the entire continuous process, which constitutes one key aspect of control strategy. Residence time distribution (RTD) play an important role in material traceability as it characterizes the material spreading through the process. The propagation of upstream disturbances could be predictively tracked through the entire process by convolution of the disturbance and the RTD. The present study sets up the RTD-based modeling framework in a commonly used process modeling environment, gPROMS, and integrates it with existing modules and built-in tools (e.g. parameter estimation). Concentration calculations based on the convolution integral requires access to historical stream property information, which is not readily available in flowsheet modeling platforms. Thus, a novel approach is taken whereby a partial differential equation is used to propagate and store historical data as the simulation marches forward in time. Other stream properties not modeled by an RTD are determined in auxiliary modules. To illustrate the application of the framework, an integrated RTD-auxiliary model for a continuous direct compression manufacturing line was developed. An excellent agreement was found between the model predictions and experiments. The validated model was subsequently used to assess in-process control strategies for feeder and material traceability through the process. Our simulation results show the employed modeling approach facilitates risk-based assessment of the continuous line by promoting our understanding on the process.

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A dimensionless analysis of residence time distributions for continuous powder mixing

Cited by 39 publications

References 6 publications

RTD-based material tracking in a fully-continuous dry granulation tableting line

RTD-based material tracking in a fully-continuous dry granulation tableting line

Continuous Mixing Technology: Characterization of a Vertical Mixer Using Residence Time Distribution

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

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