NERDG 2026
Poster 3 Abstract
Impact of polymer residual content on properties and performance of risperidone microspheres
Saurabh Bhorkade, Bo Wan, Diane Burgess
School of Pharmacy, University of Connecticut, Storrs, CT
Presenting Author: Saurabh Bhorkade
Corresponding Author: Saurabh Bhorkade, [email protected]
Purpose
Poly (lactic-co-glycolic acid) (PLGA) microspheres are widely used long acting injectables, performance of which is very sensitive to polymer properties. While studies have shown that factors such as L/G ratio, molecular weight and blockiness influence performance, the impact of residual content (monomer and solvent) in PLGA is not well understood. This study looks at how different residues affect risperidone microsphere properties and release.
Methods
Low-residual PLGA was systematically spiked with defined levels (1–5% w/w) of monomer (lactide; L1-L4 or glycolide; G1-G4) or organic solvent (hexane; S1-S4) to generate different formulations. Risperidone microspheres were prepared using same emulsification and solvent evaporation conditions and evaluated for particle size, drug loading, morphology, in vitro release and degradation.
Results
It was observed that microsphere properties were impacted by type and concentration of residual content. For example, lactide-spiked formulations showed minimal variation in particle size with consistent drug loading (~33–38% w/w), and typical triphasic in vitro release indicating that the presence of lactide residues does not significantly impact microsphere formation and release.
In contrast, glycolide-spiked microspheres exhibited smaller particle sizes with increasing glycolide content. These formulations showed faster release especially during early lag phases. Difference was also observed during in vitro degradation with early onset of pore formation and faster degradation. This could be attributed to hydrophilic nature of glycolide promoting faster water uptake and hydrolysis.
Microsphere properties were most impacted by presence solvent residues. Increasing solvent residue resulted in reduced particle size (S1 ~83µm to S4 ~69µm), decreased drug loading (S1~35% to S4 ~29%), and porous microspheres. This may be because of residual solvent decreasing the viscosity of the organic phase during primary emulsification, resulting in smaller droplets. Solvent residues also impacted the in vitro release with formulations S3 and S4 showing near zero-order release (deviating from typical triphasic release) and degradation kinetics showing much faster pore formation and erosion.
Conclusion
The nature and level of residual content significantly impacted microsphere properties. Microspheres are considered high-risk formulations, as even minor variations in their properties can lead to significant adverse effects. This work highlights the importance of controlling residual solvent levels.
Keywords
Microsphere, residual content, PLGA, in vitro release
Poster 3 Abstract
Impact of polymer residual content on properties and performance of risperidone microspheres
Saurabh Bhorkade, Bo Wan, Diane Burgess
School of Pharmacy, University of Connecticut, Storrs, CT
Presenting Author: Saurabh Bhorkade
Corresponding Author: Saurabh Bhorkade, [email protected]
Purpose
Poly (lactic-co-glycolic acid) (PLGA) microspheres are widely used long acting injectables, performance of which is very sensitive to polymer properties. While studies have shown that factors such as L/G ratio, molecular weight and blockiness influence performance, the impact of residual content (monomer and solvent) in PLGA is not well understood. This study looks at how different residues affect risperidone microsphere properties and release.
Methods
Low-residual PLGA was systematically spiked with defined levels (1–5% w/w) of monomer (lactide; L1-L4 or glycolide; G1-G4) or organic solvent (hexane; S1-S4) to generate different formulations. Risperidone microspheres were prepared using same emulsification and solvent evaporation conditions and evaluated for particle size, drug loading, morphology, in vitro release and degradation.
Results
It was observed that microsphere properties were impacted by type and concentration of residual content. For example, lactide-spiked formulations showed minimal variation in particle size with consistent drug loading (~33–38% w/w), and typical triphasic in vitro release indicating that the presence of lactide residues does not significantly impact microsphere formation and release.
In contrast, glycolide-spiked microspheres exhibited smaller particle sizes with increasing glycolide content. These formulations showed faster release especially during early lag phases. Difference was also observed during in vitro degradation with early onset of pore formation and faster degradation. This could be attributed to hydrophilic nature of glycolide promoting faster water uptake and hydrolysis.
Microsphere properties were most impacted by presence solvent residues. Increasing solvent residue resulted in reduced particle size (S1 ~83µm to S4 ~69µm), decreased drug loading (S1~35% to S4 ~29%), and porous microspheres. This may be because of residual solvent decreasing the viscosity of the organic phase during primary emulsification, resulting in smaller droplets. Solvent residues also impacted the in vitro release with formulations S3 and S4 showing near zero-order release (deviating from typical triphasic release) and degradation kinetics showing much faster pore formation and erosion.
Conclusion
The nature and level of residual content significantly impacted microsphere properties. Microspheres are considered high-risk formulations, as even minor variations in their properties can lead to significant adverse effects. This work highlights the importance of controlling residual solvent levels.
Keywords
Microsphere, residual content, PLGA, in vitro release
