Characterization of Spray Dried Particles Through Microstructural Imaging

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Spray drying is a key technique for producing amorphous solid dispersions (ASD) to enhance the bioavailability of poorly water-soluble drugs.
• Understanding the microstructure of spray-dried (SD) particles is crucial for optimizing drug product performance.

Purpose of the Study:

• To investigate the impact of spray drying parameters on the microstructure of amorphous solid dispersions (ASD).
• To develop and apply an AI-facilitated imaging analysis tool for quantitative characterization of SD particles.
• To correlate particle microstructure with physical properties and performance.

Main Methods:

• Utilized focused ion beam-scanning electron microscopy (FIB-SEM) and X-ray microcomputed tomography (XRCT) for microstructure analysis.
• Developed an artificial intelligence (AI) tool for quantitative XRCT image analysis of thousands of SD particles.
• Measured particle size distribution, envelope density, and compact tensile strength.

Main Results:

• Higher spray drying outlet temperatures (T_out) resulted in more spherical, hollow particles with thinner walls.
• Lower T_out produced raisin-like particles with thicker walls.
• AI-facilitated XRCT analysis enabled quantitative assessment of particle attributes, with envelope density proving more sensitive to process changes than bulk/tap density.
• SD particle compact tensile strength correlated with wall thickness, suggesting deformation of thinner-walled particles contributes to interparticle contact.

Conclusions:

• Spray drying conditions significantly influence SD particle morphology and microstructure.
• AI-enhanced XRCT analysis provides a powerful tool for detailed particle characterization.
• Particle microstructure, particularly wall thickness, affects mechanical properties and can inform the design of drug products with improved performance and process robustness.