Analysis of PLGA using APC-MALS

Importance of the Topic

Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer widely used in drug delivery and medical devices.
Accurate characterization of PLGA properties such as molecular weight, polydispersity, and conformation is critical for formulation performance, regulatory approval, and quality control.

Objectives and Study Overview

This study applies size exclusion chromatography with multi-angle light scattering and intrinsic viscosity detection (SEC-MALS-IV) combined with ultra-high-performance liquid chromatography (UHPLC) to measure PLGA at high speed and resolution.
Goals include absolute molecular weight determination, conformation analysis of linear versus branched structures, and investigation of different lactic acid to glycolic acid ratios (L:G ratios).

Methodology

Samples: linear and branched PLGA from PolySciTech dissolved in tetrahydrofuran (THF).
Chromatography: Waters ACQUITY Advanced Polymer Chromatography (APC) UHPLC system equipped with APC XT columns (45 Å, 125 Å, 450 Å).
Detection: SEC-MALS-IV using Wyatt microDAWN multi-angle light scattering, microViscoStar intrinsic viscosity, and microOptilab refractive index detectors.

Instrumentation Used

• Waters ACQUITY APC UHPLC system
• APC XT columns: 45 Å 4.6×150 mm, 125 Å 4.6×150 mm, 450 Å 4.6×75 mm
• Wyatt microDAWN multi-angle light scattering detector
• Wyatt microViscoStar intrinsic viscosity detector
• Wyatt microOptilab refractive index detector

Main Results and Discussion

UHPLC with low dispersion flow path delivered 2× faster analysis and 3× lower solvent use compared to conventional HPLC, supporting sustainability and cost reduction.
High signal-to-noise ratio in light scattering and refractive index traces enabled accurate molar mass determination across elution peaks.
Mark-Houwink-Sakurada plots distinguished branched from linear PLGA: branched samples showed lower slope indicating a more compact conformation at higher molecular weights.
Comparison of PLGA with L:G ratios of 85:15 and 60:40 revealed that higher glycolic acid content reduced solubility and conformation slope (0.51 vs 0.60), reflecting increased compactness.

Benefits and Practical Applications

• Absolute measurement of molecular weight and distribution without reliance on calibration standards
• Simultaneous determination of size and conformation via intrinsic viscosity
• Rapid, high-resolution separations lowering solvent consumption and operating costs
• Regulatory compliance for generic drug excipient equivalence
• Enhanced throughput for industrial R&D and quality assurance labs

Future Trends and Opportunities

Continued integration of UHPLC-compatible detectors for rapid polymer analysis.
Expansion of SEC-MALS-IV approaches to emerging biodegradable polymers and complex architectures.
Increased adoption in pharmaceutical and biomedical industries for formulation optimization and generic product demonstration.
Development of greener solvents and methods to further reduce environmental impact.

Conclusion

The combination of APC-UHPLC and Wyatt SEC-MALS-IV detectors provides a powerful platform for comprehensive PLGA characterization.
This workflow achieves faster analysis, lower solvent usage, and detailed insights into molecular weight, branching, and composition effects.
Such capabilities support formulation development, regulatory approval, and routine quality control in pharmaceutical and biomedical applications.

References

• Hadar J., Skidmore S., Garner J., Park H., Park K., Wang Y., Qin B., Jiang X. Characterization of branched poly(lactide-co-glycolide) polymers used in injectable, long-acting formulations. Journal of Controlled Release. 304:75-89 (2019).