NERDG 2026
Poster 28 Abstract
Understanding the impact of porosity on in vitro performance of PLGA microspheres
Pawan Kumar Pandey, Daniyal Saleem, Diane J. Burgess
School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA
Presenting and Corresponding Author: Pawan Kumar Pandey, [email protected]
Purpose
Poly(lactic-co-glycolic acid) microspheres are widely used in marketed long-acting injectable products to control in vivo drug release. However, their development is challenging due to inherent polymer heterogeneity (e.g., molecular weight, monomer ratio, and blockiness) which impacts product performance. Additionally, formulation and processing-induced microstructural differences impact release behavior. PLGA products generally demonstrate triphasic release profiles, with an initial burst, a lag phase, followed by a secondary release phase. The lag phase is attributed to time-dependent water ingress, polymer degradation, pore formation and enlargement, and drug solubilization. This study seeks to elucidate how microsphere porosity governs drug release and to leverage this understanding to design continous release profiles.
Methods
Porous microspheres were prepared using a modified solvent evaporation method incorporating a porogen. The non-aqueous phase consisted of PLGA (75:25, 0.28 dL/g), dichloromethane, triamcinolone acetonide, and benzyl alcohol, while the aqueous phase comprised 1% w/v PVA solution with varying porogen concentrations (0.25%, 1%, and 2%). The two phases were mixed, homogenized to form an emulsion, and dispersed in solvent extraction media. The resulting solidified microspheres were collected, washed, and lyophilized. Subsequent analyses included particle size, drug loading, encapsulation efficiency, and porosity, with in vitro release studies using a USP type IV apparatus.
Results
Three formulations with varying porogen concentrations (0.25%, 1%, and 2% w/v) were prepared. Higher particle size was observed with increased porogen concentration. However, drug loading was fairly similar for all formulations. SEM and BET analysis confirmed higher porosity with increased porogen concentration. In vitro release studies revealed minimal or no lag phase across the formulations; the 0.25% w/v porogen variant exhibited sustained release over 30 days. The addition of salt lowered the glass transition temperature and resulted in drug leakage during manufacturing, and consequently, the microspheres had lower drug loading and higher initial burst release.
Conclusion
PLGA microspheres with different microstructures were successfully prepared via solvent evaporation using ammonium bicarbonate as a porogenic agent. The porogen at low concentrations provided constant drug release and avoided the occurrence of a lag phase. High concentrations of porogens increased PLGA plasticity resulting in rapid and erratic drug release.
Keywords
PLGA, Microstructure, Long acting injectables, Polymeric particles, SEM- Scanning electron microscopy, BET- Brunauer-Emmett-Teller
Poster 28 Abstract
Understanding the impact of porosity on in vitro performance of PLGA microspheres
Pawan Kumar Pandey, Daniyal Saleem, Diane J. Burgess
School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA
Presenting and Corresponding Author: Pawan Kumar Pandey, [email protected]
Purpose
Poly(lactic-co-glycolic acid) microspheres are widely used in marketed long-acting injectable products to control in vivo drug release. However, their development is challenging due to inherent polymer heterogeneity (e.g., molecular weight, monomer ratio, and blockiness) which impacts product performance. Additionally, formulation and processing-induced microstructural differences impact release behavior. PLGA products generally demonstrate triphasic release profiles, with an initial burst, a lag phase, followed by a secondary release phase. The lag phase is attributed to time-dependent water ingress, polymer degradation, pore formation and enlargement, and drug solubilization. This study seeks to elucidate how microsphere porosity governs drug release and to leverage this understanding to design continous release profiles.
Methods
Porous microspheres were prepared using a modified solvent evaporation method incorporating a porogen. The non-aqueous phase consisted of PLGA (75:25, 0.28 dL/g), dichloromethane, triamcinolone acetonide, and benzyl alcohol, while the aqueous phase comprised 1% w/v PVA solution with varying porogen concentrations (0.25%, 1%, and 2%). The two phases were mixed, homogenized to form an emulsion, and dispersed in solvent extraction media. The resulting solidified microspheres were collected, washed, and lyophilized. Subsequent analyses included particle size, drug loading, encapsulation efficiency, and porosity, with in vitro release studies using a USP type IV apparatus.
Results
Three formulations with varying porogen concentrations (0.25%, 1%, and 2% w/v) were prepared. Higher particle size was observed with increased porogen concentration. However, drug loading was fairly similar for all formulations. SEM and BET analysis confirmed higher porosity with increased porogen concentration. In vitro release studies revealed minimal or no lag phase across the formulations; the 0.25% w/v porogen variant exhibited sustained release over 30 days. The addition of salt lowered the glass transition temperature and resulted in drug leakage during manufacturing, and consequently, the microspheres had lower drug loading and higher initial burst release.
Conclusion
PLGA microspheres with different microstructures were successfully prepared via solvent evaporation using ammonium bicarbonate as a porogenic agent. The porogen at low concentrations provided constant drug release and avoided the occurrence of a lag phase. High concentrations of porogens increased PLGA plasticity resulting in rapid and erratic drug release.
Keywords
PLGA, Microstructure, Long acting injectables, Polymeric particles, SEM- Scanning electron microscopy, BET- Brunauer-Emmett-Teller
