A novel methodology to study polymodal particle size distributions produced during continuous wet granulation

Area of Science:

• Chemical Engineering
• Materials Science
• Pharmaceutical Technology

Background:

• Achieving homogeneous particle size distribution is critical in powder granulation, particularly for pharmaceutical applications.
• Traditional metrics like d50 and span are insufficient for evaluating homogeneity in polymodal particle size distributions.
• Limitations of existing methods necessitate a more robust characterization tool.

Purpose of the Study:

• To demonstrate the ineffectiveness of the span parameter for quantifying particle size homogeneity in granulation.
• To propose and validate a novel homogeneity factor for improved characterization of particle size distribution.
• To identify critical process parameters influencing granule homogeneity.

Main Methods:

• Development of a novel homogeneity factor derived from particle size distribution curves, ranging from 0 to 100%.
• Application of the homogeneity factor to analyze granules produced using an 11mm twin screw granulator.
• Characterization of granule production for two excipients: α-lactose monohydrate and microcrystalline cellulose.

Main Results:

• The novel homogeneity factor effectively quantifies particle size distribution, unlike the traditional span parameter.
• Granule homogeneity varied significantly (0-95%) within the defined workspace of the twin screw granulator.
• Identification of critical process parameters (feed rate, liquid/solid ratio, torque velocities) impacting homogeneity.

Conclusions:

• The proposed homogeneity factor offers a superior method for assessing particle size uniformity in granulation processes.
• Optimal operational conditions for producing highly homogeneous granules (5µm-2.2mm) were determined for both tested materials.
• This approach enhances process understanding and control in pharmaceutical powder granulation.