Investigation into process-induced de-aggregation of cohesive micronised API particles

Area of Science:

• Pharmaceutical Science
• Chemical Engineering
• Materials Science

Background:

• Cohesive micronized active pharmaceutical ingredients (APIs) present challenges in achieving homogeneous pharmaceutical formulations.
• Understanding the impact of unit processes on API de-aggregation is crucial for formulation development.

Purpose of the Study:

• To evaluate the effectiveness of different unit processes in de-aggregating a cohesive micronized API within a pharmaceutical blend.
• To assess the influence of these processes on primary API particle characteristics.

Main Methods:

• Near-infrared chemical imaging (NIR-CI) was employed to analyze the distribution of API-rich domains.
• An image-based particle characterization system with Raman analysis was used for primary particle assessment.
• The study compared blending, cone milling, and powder feed transmission (Alexanderwerk WP120).

Main Results:

• Initial blending resulted in inhomogeneous distribution of large API-rich domains.
• Cone milling reduced, but did not eliminate, API-rich domains.
• Powder feed transmission, both with and without prior milling, completely dispersed remaining aggregates.
• The Alexanderwerk WP120 system demonstrated superior aggregate dispersion compared to the blend-mill-blend step.
• Primary micronized API particle size remained unaffected by powder feed transmission.

Conclusions:

• The Alexanderwerk WP120 powder feed system effectively de-aggregates cohesive micronized APIs in pharmaceutical formulations.
• This powder feed system induces sufficient shear for aggregate dispersion, outperforming traditional milling in this context.
• The findings support the powder feed system as a key unit operation for enhancing homogeneity in cohesive formulations.