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Background <p>In continuous manufacturing (CM), raw materials undergo an uninterrupted transformation, with products that are discharged continuously. A thorough understanding of process dynamics ensures stable operation and effective control. Residence time distribution (RTD) is a crucial tool for characterizing material flow and mixing phenomena within CM. With the increasing adoption of CM, RTD has been extensively studied, proving to be an effective tool for process design, optimization, and control.</p> Area covered <p>This review article provides a comprehensive discussion of the experimental approaches, modeling techniques, and applications of RTD methodology in CM. A detailed explanation of the fundamental principles of RTD is provided, followed by an in-depth analysis of measurement procedures, with a particular focus on powder-based systems. Additionally, various applications of RTD in CM processes are explored, highlighting key factors influencing RTD across different unit operations, especially in solid dosage manufacturing.</p> Expert opinion <p>As CM continues to gain traction, RTD has become increasingly valuable in the pharmaceutical industry, demonstrating its utility across various unit operations, including continuous feeders, continuous blenders, twin-screw wet granulators, roller compactors, and tablet presses. In pharmaceutical CM, RTD serves as a valuable tool for material traceability, diversion of out-of-specification products, and real-time prediction of product quality. Its application aligns with the principles of Quality-by-Design (QbD) and supports the development of robust control strategies in CM. Moving forward, further advancements in RTD applications are anticipated, enhancing process understanding and strengthening control strategies for CM.</p>

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Understanding and development of residence time distribution (RTD) model in continuous manufacturing

  • 期刊论文

  • 发表日期：

    2025年4月30日

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  • Hae Woo Lee,
  • Dongsik Park

摘要

Background

In continuous manufacturing (CM), raw materials undergo an uninterrupted transformation, with products that are discharged continuously. A thorough understanding of process dynamics ensures stable operation and effective control. Residence time distribution (RTD) is a crucial tool for characterizing material flow and mixing phenomena within CM. With the increasing adoption of CM, RTD has been extensively studied, proving to be an effective tool for process design, optimization, and control.

Area covered

This review article provides a comprehensive discussion of the experimental approaches, modeling techniques, and applications of RTD methodology in CM. A detailed explanation of the fundamental principles of RTD is provided, followed by an in-depth analysis of measurement procedures, with a particular focus on powder-based systems. Additionally, various applications of RTD in CM processes are explored, highlighting key factors influencing RTD across different unit operations, especially in solid dosage manufacturing.

Expert opinion

As CM continues to gain traction, RTD has become increasingly valuable in the pharmaceutical industry, demonstrating its utility across various unit operations, including continuous feeders, continuous blenders, twin-screw wet granulators, roller compactors, and tablet presses. In pharmaceutical CM, RTD serves as a valuable tool for material traceability, diversion of out-of-specification products, and real-time prediction of product quality. Its application aligns with the principles of Quality-by-Design (QbD) and supports the development of robust control strategies in CM. Moving forward, further advancements in RTD applications are anticipated, enhancing process understanding and strengthening control strategies for CM.