Aging-induced microstructural evolution in risperidone loaded PLGA microspheres.

This study demonstrates the application of innovative imaging-based characterization techniques to quantify structural changes as a function of ageing for poly (lactic-co glycolic acid) (PLGA) microspheres. Aging of polymers can potentially alter the performance of polymer-based therapeutics and therefore an understanding of the impact of aging on microsphere structure is important. Correlative focused ion beam scanning electron microscopy (FIB-SEM) and X-ray microscopy (XRM) were used to quantify the change in structural critical quality attributes (CQAs) of risperidone loaded microspheres at the single microsphere scale and overall batch scale. One batch of microspheres was aged one year beyond its shelf life while the other batch was within its shelf life, providing a robust comparison between an aged and fresh sample. Comparison of the aged and fresh microspheres revealed an increase in porosity and pore size following aging at the nanoscale, anticipated with physical relaxation of the PLGA. A novel XRM-based method to determine the material density of the microsphere batches was employed to assess the batch level changes induced by aging. A decrease in density in the aged microsphere batch was observed, that was consistent with the porosity increase seen in the FIB-SEM study. These results reveal aging produces an increase in porosity through polymer relaxation that widens the existing pores within the microspheres. The increased porosity was correlated to the in vitro release performance of the two microsphere batches, providing a novel method to assess the impact of polymer aging on the downstream performance of PLGA microsphere systems.