Evaluating Degradation of Drug Delivery Polymers Using Advanced Polymer Chromatography (APC) with Light Scattering and Viscometry

Significance of the Topic

The controlled degradation of drug delivery polymers is essential for tailoring release profiles, improving therapeutic efficacy, and ensuring biocompatibility. Understanding how sterilization and other processing steps affect polymer molecular weight and structure directly influences formulation stability and patient safety.

Objectives and Study Overview

This application note evaluates the impact of radiation sterilization on a PLA-PEO-PLA triblock copolymer. By comparing virgin and irradiated samples, the study demonstrates the use of Advanced Polymer Chromatography (APC) coupled with multi-detection (light scattering and viscometry) to quantify changes in molecular properties efficiently and accurately.

Methodology

Samples of virgin and two irradiated PLA-PEO-PLA copolymers were dissolved in tetrahydrofuran (THF) at 1 mg/mL. Separations were performed at 40 °C using three ACQUITY APC XT columns in series (45 Å, 125 Å, 450 Å) with a 1.0 mL/min THF mobile phase. Eluent passed directly through an OMNISEC REVEAL module containing refractive index, right- and low-angle light scattering, and intrinsic viscosity detectors. Calibration employed NIST-traceable polystyrene standards.

Instrumentation Used

• Waters ACQUITY APC System with ACQUITY APC XT Columns
• Malvern Panalytical OMNISEC REVEAL multi-detector module (RI, LS at 90°/7°, viscometer)
• ACQUITY APC standalone console and OMNISEC data acquisition software

Key Results and Discussion

APC reduced run times and solvent consumption by more than half compared to traditional SEC, enhancing throughput and sustainability. Multi-detector chromatograms revealed that irradiation led to a two-thirds reduction in number-average (Mn) and weight-average (Mw) molecular weights. Intrinsic viscosity and hydrodynamic radius decreased proportionally, indicating chain scission without structural branching or crosslinking. Mark–Houwink overlays confirmed identical polymer conformation before and after irradiation, with shifts corresponding only to lower molecular weight fractions.

Benefits and Practical Applications

• Rapid, high-resolution molecular weight profiling enables quality control of biodegradable polymers.
• Absolute molar mass and intrinsic viscosity measurements support mechanism elucidation of degradation.
• Reduced solvent use lowers operational costs and environmental impact.
• Integrated multi-detector setup simplifies workflow for R&D and QC laboratories.

Future Trends and Opportunities

Advancements in ultrahigh-pressure polymer chromatography and detector miniaturization will further accelerate analysis and reduce dispersion. Coupling APC with mass spectrometry or chromatography under greener solvent systems could expand polymer characterization capabilities. Emerging biodegradable polymer architectures and stimuli-responsive materials will benefit from these high-throughput, multi-detector approaches.

Conclusion

The combination of Waters ACQUITY APC and Malvern Panalytical OMNISEC REVEAL provides a powerful platform for rapid, detailed characterization of polymer degradation. This approach delivers accurate molar mass, dispersity, and conformation data with reduced solvent consumption, enabling more sustainable and efficient drug delivery polymer development.

References

Meeker L., Pothecary M. Evaluating Degradation of Drug Delivery Polymers Using Advanced Polymer Chromatography with Light Scattering and Viscometry. Waters Corporation & Malvern Panalytical, 2019.