Probing the interplay between drug saturation, processing temperature and microstructure of amorphous solid...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing drug solubility and bioavailability.
• Hot-melt extrusion (HME) is a key manufacturing process for ASDs, but its impact on microstructure requires detailed investigation.
• Understanding drug saturation and processing parameters is vital for controlling ASD properties.

Purpose of the Study:

• To investigate the influence of drug saturation and HME processing on ASD microstructure.
• To correlate processing conditions with drug solubility and ASD structural features.
• To elucidate the formation of microstructures and their implications for product stability.

Main Methods:

• Utilized HME with varying drug loadings and temperatures to achieve different drug saturation levels.
• Employed in-line low-frequency Raman spectroscopy to monitor the process and construct solubility phase diagrams.
• Analyzed ASDs using synchrotron X-ray phase-contrast micro computed tomography (Sync-XPC-μCT) with advanced image segmentation.

Main Results:

• Sync-XPC-μCT identified diverse structural domains: crystalline clusters, impurities, polymer heterogeneities, and pores.
• Supersaturated ASDs (>20 wt% drug loading) exhibited greater structural complexity and defective crystalline domains upon ageing.
• HME processing regime significantly affected polymer homogeneity, porosity, and pore connectivity.

Conclusions:

• Drug saturation and HME processing critically influence ASD microstructure and stability.
• Supersaturated ASDs are prone to forming defective crystalline structures, impacting long-term stability.
• Correlating solubility data with microstructural analysis provides insights into ASD formation dynamics and performance.