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Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

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Analyzing Spatial Variations in Molecular Mobility in Hydrated Amorphous Drug-Polymer Blends Using Fourier Transform

Michelle L Cousineau¹, Maura M Wimsatt², Garth J Simpson²

¹Department of Industrial and Molecular Pharmaceutics, Purdue University, West Lafayette, Indiana 47907, United States.

The Journal of Physical Chemistry. B

|June 16, 2026

Summary

Amorphous solid dispersions (ASDs) can improve drug bioavailability but face stability issues. This study uses advanced imaging to link drug loading, phase separation, and release, offering a new tool for ASD formulation.

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Area of Science:

Materials Science
Pharmaceutical Sciences
Physical Chemistry

Background:

Amorphous solid dispersions (ASDs) enhance oral bioavailability of poorly soluble drugs.
Hydration-induced phase separation in ASDs complicates drug release and stability.
Understanding molecular mobility within hydrating ASDs is crucial for formulation.

Purpose of the Study:

To quantify phase-resolved molecular mobility in hydrating ibuprofen-copovidone ASDs.
To correlate drug loading, phase morphology, and drug release kinetics.
To establish segmented Fourier transform fluorescence recovery after photobleaching (FT-FRAP) as a diagnostic tool for ASDs.

Main Methods:

Integration of FT-FRAP with image segmentation in a "glass-sandwich" hydration platform.
Confocal fluorescence microscopy to visualize phase morphology.
Dynamic light scattering to characterize released nanodroplets.
Release studies of ibuprofen-copovidone ASDs at different drug loadings (10% and 15% w/w).

Main Results:

10% DL ibuprofen ASD showed rapid release with dispersed hydrophobic domains.
15% DL ASD exhibited poor release due to a persistent drug-rich barrier.
FT-FRAP revealed distinct molecular mobilities and local viscosities across different phases (gel, aqueous, ibuprofen-rich) within the hydrated ASD matrix.
Nanodroplets (520 ± 8 nm) were observed in solutions released from the 10% DL ASD.

Conclusions:

A quantitative link between drug loading, phase morphology, local mobility, and macroscopic release was established.
Segmented FT-FRAP effectively diagnoses ASD failure mechanisms by resolving microheterogeneity.
This technique guides the formulation of stable, high-loading ASDs with predictable drug release.