Assessing microstructural critical quality attributes in PLGA microspheres by FIB-SEM analytics

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Biotechnology

Background:

• Active pharmaceutical ingredient (API) distribution in controlled-release drug products is a critical quality attribute (CQA).
• Accurate characterization of phase distributions is essential for evaluating performance and microstructure equivalence.
• Poly(lactic-co-glycolic acid) (PLGA) microspheres are widely used for controlled drug delivery.

Purpose of the Study:

• To quantitatively characterize polymer, API, and porosity distributions in PLGA microspheres.
• To develop a predictive model for controlled drug release based on microstructural data.
• To establish a correlation between microstructural CQAs and formulation/manufacturing parameters.

Main Methods:

• Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) for high-resolution imaging.
• Quantitative artificial intelligence (AI) image analytics for distribution analysis.
• 3D model reconstruction and numerical simulation for drug release prediction.

Main Results:

• Identified microstructural CQAs including API, polymer, and microporosity abundance, domain size, and distribution.
• Validated an image-based drug release modeling method through agreement with in vitro experiments.
• Demonstrated the dependence of drug release on API particle distribution/size and microsphere porosity.

Conclusions:

• This study presents the first quantitative and predictive correlation between microstructural CQAs derived from imaging and formulation/manufacturing parameters in PLGA microspheres.
• The combined FIB-SEM and AI approach offers a powerful tool for characterizing and optimizing controlled-release drug delivery systems.
• Accurate microstructural characterization is key to understanding and controlling drug release profiles.