A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to...

Area of Science:

• Pharmaceutical Technology
• Process Engineering
• Materials Science

Background:

• Controlled release drug delivery systems are crucial for therapeutic efficacy.
• Fluid bed technology offers advantages for coating multiparticulate systems.
• Understanding critical process parameters (CPP) is essential for reproducible manufacturing.

Purpose of the Study:

• To apply risk assessment and design of experiments (DoE) for process understanding.
• To identify critical process parameters (CPP) in manufacturing controlled release multiparticulate beads.
• To investigate the influence of CPP on film formation and critical quality attributes (CQA) using novel disk-jet fluid bed technology.

Main Methods:

• Utilized Ishikawa fish bone diagram and Failure Mode and Effects Analysis (FMEA) for risk assessment.
• Employed resolution V and IV fractional factorial designs to explore high-risk attributes and identify CPP.
• Monitored microclimate, atomization pressure, air volume, temperature, curing time, and solids percentage.
• Measured responses including agglomeration, fines, yield, particle size, assay, and drug release rate.
• Employed Pyrobuttons® for real-time temperature and humidity monitoring.

Main Results:

• Systematic risk assessment identified key factors influencing the coating process.
• Statistical DoE studies successfully mapped the relationships between process parameters and CQAs.
• Identified specific CPPs impacting film formation, process efficiency, and curing extent.
• Developed models for understanding the novel disk-jet fluid bed coating process.

Conclusions:

• Risk assessment and DoE are effective tools for understanding novel fluid bed technologies.
• Identification of CPPs enables optimization of controlled release bead manufacturing.
• This systematic approach facilitates the development of robust and reproducible pharmaceutical processes.