Particle engineering of a needle-like active pharmaceutical ingredient into size controlled agglomerates: Part I....

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Optimizing crystal size and shape is crucial for pharmaceutical solid oral dosage forms.
• Spherical agglomeration enhances powder properties but faces scalability challenges for small sizes.
• Active pharmaceutical ingredients (APIs) often exhibit challenging particle characteristics.

Purpose of the Study:

• To develop and optimize an intensified spherical agglomeration process for producing small agglomerates (<300 µm) of an API with challenging properties.
• To investigate the impact of key process variables on agglomerate attributes and bulk powder properties.
• To assess the scalability and drying efficiency of the developed process.

Main Methods:

• Spherical agglomeration integrated with a high shear wet mill.
• Multivariate Design-of-Experiment (DOE) to study bridging liquid addition time, bridging liquid to solids ratio, and wet milling speed.
• Agitated-filter isolation and drying studies.

Main Results:

• Optimized conditions yielded robust agglomerates with a median size of 30-300 µm.
• The process demonstrated scalability in agitated stirred-tanks (250 mL–5 L) for target sizes (35 µm, 80 µm, 145 µm).
• Minimal residual solvent and good flow performance were achieved; proper drying agitation preserved agglomerate integrity.

Conclusions:

• The intensified spherical agglomeration process effectively engineered API particle size, shape, density, and flowability.
• This particle engineering technique offers significant potential for pharmaceutical manufacturing and downstream processing.
• Achieving small, scalable agglomerate sizes with improved properties was successfully demonstrated.