Resolving drug release mechanisms of amorphous solid dispersions using optical coherence tomography

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Biomedical Engineering

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing the solubility and bioavailability of poorly soluble drugs.
• Hot-melt extrusion (HME) is a widely used technique for manufacturing ASDs.
• Understanding the in-situ drug release mechanisms of ASDs is essential for formulation optimization.

Purpose of the Study:

• To investigate the drug release mechanisms of ritonavir-Soluplus® ASDs prepared by HME.
• To utilize optical coherence tomography (OCT) for real-time, non-destructive visualization of dissolution processes.
• To establish a link between structural evolution and drug release kinetics in HME ASDs.

Main Methods:

• Preparation of ritonavir-Soluplus® extrudates using twin-screw HME.
• In-situ OCT imaging and UV-vis spectroscopy during dissolution in a 3D-printed flow cell.
• Machine learning-based image processing for quantitative analysis of structural changes.

Main Results:

• A multiphase dissolution mechanism involving film formation, polymer swelling, delamination, and erosion was identified.
• Drug loading above 14% w/w delayed release onset, extended swelling, and reduced overall release efficiency.
• OCT data correlated with UV-vis profiles, showing load-dependent swelling, slower erosion, and prolonged structural integrity at higher drug loadings.

Conclusions:

• Integrated OCT and UV-vis spectroscopy provide real-time insights into ASD dissolution mechanisms.
• Drug loading significantly influences structural transformations and release kinetics in HME ASDs.
• This methodology offers a powerful tool for optimizing ASD formulations and predicting drug release behavior.