Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA...

Area of Science:

• Polymer Science and Engineering
• Pharmaceutical Manufacturing
• Drug Delivery Systems

Background:

• Biodegradable polymeric microspheres are successful 3rd generation drug delivery systems, with numerous Poly (lactic-co-glycolic acid) (PLGA) products on the market.
• Continuous manufacturing is established for oral solids but not yet for polymeric injectable microspheres due to knowledge gaps.
• Current production of polymeric injectable microspheres relies on traditional batch manufacturing.

Purpose of the Study:

• To establish a novel semi-continuous manufacturing streamline for Poly (lactic-co-glycolic acid) (PLGA) and mPEG-PLGA microspheres.
• To integrate micro-mixers and real-time monitoring for efficient upscaling and process control.
• To investigate the relationship between process parameters, material attributes, and quality attributes for robust production.

Main Methods:

• Integration of micro-mixer emulsification modules with Raman spectroscopy and focused beam reflectance measurement for real-time monitoring.
• Development of an end-to-end semi-continuous manufacturing process using mPEG-PLGA for Gallic acid encapsulation.
• Investigation of critical process parameters, material attributes, and quality attributes for process robustness.

Main Results:

• Successful establishment of a semi-continuous manufacturing streamline for PLGA/PEG-PLGA microspheres.
• Demonstration of efficient upscaling flexibility and improved process understanding.
• Elaboration of the time-space evolution and mechanism of microsphere formation with specific morphology.

Conclusions:

• The developed semi-continuous process offers lower production costs, reduced process variability, and a smaller environmental footprint.
• Application of in-process control and Quality by Design (QbD) principles to complex microsphere production.
• This work builds confidence in industrial development and establishes best practices for future PLGA microsphere manufacturing, potentially marking a significant advancement.