Aging-induced microstructural evolution in risperidone loaded PLGA microspheres.

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Polymer Chemistry

Background:

• Polymer aging can affect the performance of drug delivery systems.
• Understanding structural changes in poly (lactic-co glycolic acid) (PLGA) microspheres due to aging is crucial for therapeutic efficacy.
• Microsphere structural integrity is vital for predictable drug release profiles.

Purpose of the Study:

• To quantify structural changes in PLGA microspheres as a function of aging using advanced imaging techniques.
• To compare aged and fresh microsphere batches to understand the impact of aging on critical quality attributes (CQAs).
• To correlate observed structural changes with in vitro drug release performance.

Main Methods:

• Correlative focused ion beam scanning electron microscopy (FIB-SEM) and X-ray microscopy (XRM) were employed for nanoscale and batch-level structural characterization.
• A novel XRM-based method was developed to determine material density.
• Aged (one year past shelf life) and fresh microsphere batches were analyzed.

Main Results:

• Aging led to increased porosity and pore size at the nanoscale, attributed to PLGA physical relaxation.
• A decrease in material density was observed in the aged microsphere batch.
• Increased porosity correlated with altered in vitro drug release performance.

Conclusions:

• Polymer aging in PLGA microspheres causes increased porosity via relaxation, widening existing pores.
• Advanced imaging techniques effectively quantify aging-induced structural changes.
• This study provides a novel method to assess the impact of polymer aging on PLGA microsphere drug delivery systems.