Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing

Mateo-Ortiz, Daniel; Villanueva-López, Vladimir; Muddu, Shashank Venkat; Doddridge, Gregory; Alhasson, Dana; Dennis, Michael C.

doi:10.1208/s12249-021-02148-x

Cited by 6 publications

(9 citation statements)

References 38 publications

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“…In the context of pharmaceutical manufacturing, mixing is extremely important as homogeneity is one of the deciding factors in quality control. As the industry transitions to continuous manufacturing, twin screw extruders (TSE) have been the primary mixing tool in drug manufacturing as it offers superior mixing characteristics and it is better characterized than other mixing techniques such as tumbler mixers [149] and paddle mixing [150,151] . Specifically, TSE is frequently used to mix APIs with polymers, which act as drug depots and drug release retardants upon cooling and solidification [152] .…”

Section: Unit Operationsmentioning

confidence: 99%

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Hyer,

Gregory,

Kay

et al. 2024

Adv Synth Catal

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The pharmaceutical industry has traditionally employed batch processing as a means of synthesizing active pharmaceutical ingredients (APIs) on a commercial scale. Batch manufacturing enables API synthesis in large quantities in order to meet regulations. Yet, this strategy remains cumbersome, is labor‐intensive, and creates complex logistical networks. In recent decades, batch API processing has gradually eroded American economic competitiveness and has led to the off‐shoring of API manufacturing from the United States. Today it is estimated that +80% of APIs are manufactured overseas. Meanwhile, disruptions from the Coronavirus Disease (SARS‐CoV‐2) have exacerbated weaknesses in the global supply chain, culminating with widespread shortages of critical life‐saving drugs. These shortages have emphasized the importance of reshoring drug manufacturing to the U.S. and fostered a regulatory landscape that seeks advanced methods of API manufacturing in order to bolster America’s supply chain resiliency. Recently, increased attention has been directed towards continuous drug manufacturing to enable nonstop API production within modular stand‐alone flow systems. Continuous manufacturing (CM) facilitates modular automation, offers new avenues towards process intensification, and even enables in‐line analytical monitoring from raw materials to packaged products. This strategy offers better conversion, increased safety, reduced waste, and overall cost savings versus traditional batch‐style processing. The rise of advanced API manufacturing, coupled with the current regulatory landscape, offers a rare window of opportunity to convert traditional batch pharmaceutical processes into continuous, streamlined production systems to on‐shore API manufacturing and eliminate drug shortages. This review will outline the current state‐of‐the‐art in the CM of APIs and will highlight the translation of chemistry and unit operations from batch processes to modular CM systems.

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Section: Unit Operationsmentioning

confidence: 99%

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Hyer,

Gregory,

Kay

et al. 2024

Adv Synth Catal

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“…TSG, or continuous granulation procedures, provide several potential advantages over batch granulation processes. These include a smaller equipment footprint, enhanced process control and consistency, and greater flexibility in handling various formulations [ 86 , 87 ]. The incorporation of many unit activities, including powder feeding, mixing, granulation, and drying, into a single continuous process enhances the appeal of TSG as a platform for the application of quality by design (QbD) and process analytical technology (PAT) principles [ 87 , 88 ].…”

Section: Simulation Of Twin-screw Granulationmentioning

confidence: 99%

“…Nevertheless, achieving successful growth and expansion of TSG processes necessitates a profound comprehension of the intricate interaction of equipment design, operating circumstances, and material qualities. The screw configuration, barrel fill level, liquid addition method, and binder qualities can all have a substantial influence on the formation and growth of granules, as well as the quality attributes of the final product [ 9 , 87 , 89 ]. Obtaining a comprehensive knowledge of this process merely through experimental investigation is difficult because of the lack of transparency in the multiphase system, the brief duration of the process, and the limited opportunities for sampling and monitoring during the process.…”

Section: Simulation Of Twin-screw Granulationmentioning

confidence: 99%

“…Mateo-Ortiz, Villanueva-Lopez, Muddu, and Doddridge [ 87 ] examined the practicability of blending dry powders in the pre-melting regions of a twin-screw extruder through the utilisation of DEM modelling and near-infrared (NIR) spectroscopy [ 87 ]. The authors’ objective was to integrate the blending and extrusion/granulation processes into a single apparatus, thereby facilitating continuous manufacturing and enhancing process efficiency.…”

Section: Simulation Of Twin-screw Granulationmentioning

confidence: 99%

“…The study used DEM simulations with the Hertz–Mindlin contact model to obtain insights into the mixing patterns within the extruder at the particle level. This information was then used to assist in the selection of the screw configuration prior to conducting experiments [ 87 ]. The angle of repose test was used to calibrate the parameters of the DEM model.…”

Section: Simulation Of Twin-screw Granulationmentioning

confidence: 99%

See 2 more Smart Citations

Process Simulation of Twin-Screw Granulation: A Review

Arthur,

Rahmanian

2024

Pharmaceutics

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Twin-screw granulation has emerged as a key process in powder processing industries and in the pharmaceutical sector to produce granules with controlled properties. This comprehensive review provides an overview of the simulation techniques and approaches that have been employed in the study of twin-screw granulation processes. This review discusses the major aspects of the twin-screw granulation process which include the fundamental principles of twin-screw granulation, equipment design, process parameters, and simulation methodologies. It highlights the importance of operating conditions and formulation designs in powder flow dynamics, mixing behaviour, and particle interactions within the twin-screw granulator for enhancing product quality and process efficiency. Simulation techniques such as the population balance model (PBM), computational fluid dynamics (CFD), the discrete element method (DEM), process modelling software (PMS), and other coupled techniques are critically discussed with a focus on simulating twin-screw granulation processes. This paper examines the challenges and limitations associated with each simulation approach and provides insights into future research directions. Overall, this article serves as a valuable resource for researchers who intend to develop their understanding of twin-screw granulation and provides insights into the various techniques and approaches available for simulating the twin-screw granulation process.

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A CFD model with free surface tracking: predicting fill level and residence time in a starve-fed single-screw extruder

Olofsson

Roland

Spangenberg

et al. 2023

Int J Adv Manuf Technol

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Mixing in extrusion is a vital part of achieving consistent and high-quality extrudates, with residence time being an elucidative measure of the mixing performance. Recent studies around numerical modeling of residence time distributions in single-screw extruders appear to consider flooded extruders mainly. This paper introduces a new and general CFD model to characterize the extruder fill length and residence time distribution for a viscoplastic ceramic material in a starve-fed extruder, including free surface tracking. The CFD model simulates a pulse-injection test, where a fluid parcel is injected at the inlet, with subsequent outlet concentration measured over time. The study includes material characterization and model validation based on laboratory tests. Results quantify the impact of accounting for the partially filled extruder instead of assuming it to be flooded, addressing the potential error when only considering simple analytical approximations to calculate system average residence times. Results further show the ability to fit simulation results to more simple analytical models. This underlines the importance of including the entire extrusion system and forming the basis for further work toward enabling real-time model predictions in starve-fed extrusion systems.

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Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing

Cited by 6 publications

References 38 publications

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Process Simulation of Twin-Screw Granulation: A Review

A CFD model with free surface tracking: predicting fill level and residence time in a starve-fed single-screw extruder

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