Residual Content Impacts Critical Quality Attributes and Performance of Risperidone Microspheres

Poly (lactic-co-glycolic acid) (PLGA) microspheres are widely used long-acting injectable depots. However, their performance is highly sensitive to polymer material attributes that can influence microsphere structure, degradation, and drug release. While factors such as molecular weight and monomer ratio are well recognized, impact of residual species present in commercial PLGA has not been systematically evaluated. The novelty of the present study is the investigation of the effect of PLGA residual content on the physicochemical characteristics and in vitro performance of risperidone-loaded PLGA microspheres.

PLGA with varying amounts of residual content was obtained either through purification of a high-residual polymer by reprecipitation or by deliberately spiking PLGA with controlled quantities of monomeric residues (lactide or glycolide) or organic solvent. Risperidone was selected as the model drug, and microsphere formulations were prepared using PLGA with different amounts of residual content and compared with microspheres prepared using low residual PLGA. The microspheres were characterized for particle size, surface morphology, porosity, drug loading, polymer degradation kinetics, and in vitro drug release.

Residual content was shown to significantly influence microsphere formation and performance. High solvent residue had a great impact on microsphere particle size, porosity, and drug loading, resulting in accelerated polymer degradation and drug release. A clear correlation was established between residual content, microsphere structure, degradation behavior, and release kinetics.

These findings identify residual species as a critical material attribute of PLGA microspheres and highlight the importance of polymer purification and raw-material control to ensure consistent performance of microsphere formulations.