The interprocess NIR sampling as an alternative approach to multivariate statistical process control for identifying...

Area of Science:

• Pharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Materials Science

Background:

• Variability in pharmaceutical manufacturing can compromise final product quality.
• Traditional process monitoring may not always identify root causes efficiently.
• Proton-pump inhibitor enteric-coated pellets require precise control over manufacturing steps.

Purpose of the Study:

• To present a novel interprocess Near-Infrared (NIR) sampling technique for identifying manufacturing variability.
• To develop and validate a multivariate statistical process control (MSPC) model for enteric-coated pellet production.
• To compare the effectiveness of NIR-based methods with established MSPC procedures.

Main Methods:

• Interprocess NIR measurements of intermediate materials after each unit operation.
• Development of provisional NIR calibration models.
• Construction and application of a multivariate statistical process control (MSPC) model.
• Experimental analysis of pellet core properties and coating performance.

Main Results:

• Both interprocess NIR sampling and MSPC identified extrusion/spheronization parameters and lactose characteristics as critical.
• The proposed NIR approach offers quicker and easier identification of variability sources.
• Changes in lactose characteristics significantly impacted extrusion/spheronization, leading to larger, fragile pellet cores.
• Pellet fragility resulted in breakage during fluid bed operations, compromising enteric film coating.

Conclusions:

• Interprocess NIR sampling provides an efficient alternative for identifying manufacturing variability sources.
• Lactose characteristics are a key factor influencing extrusion/spheronization performance and subsequent coating quality.
• Understanding these relationships is crucial for optimizing the production of proton-pump inhibitor enteric-coated pellets.