Using residence time distribution in pharmaceutical solid dose manufacturing - A critical review

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Analytical Technology

Background:

• Continuous manufacturing (CM) offers improved quality and efficiency for pharmaceutical solid dosage forms, aligning with FDA's quality-by-design principles.
• Accurate predictive models for unit operations are essential for CM's full utilization, requiring a deep understanding of process characteristics.
• Residence Time Distribution (RTD) is a key tool for characterizing mixing and developing predictive models in pharmaceutical manufacturing.

Purpose of the Study:

• To address the lack of standardized guidelines for Residence Time Distribution (RTD) studies in pharmaceutical manufacturing.
• To provide a detailed review and critical discussion of RTD studies to prevent implementation errors.
• To aid in developing standardized guidelines for RTD implementation and assessment.

Main Methods:

• Reviewing and critically discussing existing literature on RTD studies in pharmaceutical manufacturing.
• Dividing the review into two main sections: determination of RTD and applications of RTD.
• Examining experimental approaches, data acquisition, pre-treatment, modeling, metrics, and limitations of RTD for solid dose manufacturing.

Main Results:

• Identified ambiguity in current RTD study implementation due to a lack of standardization by regulatory agencies.
• Detailed the steps for RTD determination, including experimental design, data handling, modeling, and metric selection.
• Highlighted critical considerations and limitations of RTD for solid dose manufacturing.

Conclusions:

• Standardized guidelines for RTD studies are necessary to ensure accurate implementation and reliable predictive modeling in pharmaceutical CM.
• The review provides a foundation for developing these guidelines, improving process understanding and control.
• Further research into RTD applications and limitations will enhance its utility in solid dose manufacturing.