Improving powder flow properties of a direct compression formulation using a two-step glidant mixing process

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• High-dose direct compression formulations present challenges in powder flow due to high drug content (30%).
• Optimizing powder flow is crucial for efficient manufacturing and consistent drug product quality.
• Conventional one-step glidant mixing may not adequately address varying powder properties.

Purpose of the Study:

• To compare a novel two-step glidant mixing operation with conventional one-step methods.
• To enhance powder flow properties of high-dose direct compression formulations.
• To determine optimal glidant types and concentrations for different powder components.

Main Methods:

• Investigated a two-step mixing process involving active pharmaceutical ingredient (API)-glidant and excipient-glidant combinations.
• Compared results with a conventional one-step glidant mixing process.
• Evaluated powder flow using angle of repose and critical orifice diameter measurements.

Main Results:

• The two-step operation allowed tailored glidant selection (0.5% nonporous silica for API, 1.0% porous silica for excipients).
• Achieved significantly improved powder flow: angle of repose of 43° and critical orifice diameter of 10 mm.
• Outperformed the one-step operation (47° angle of repose, 16 mm critical orifice diameter).

Conclusions:

• The two-step glidant mixing operation demonstrably enhances powder flow for high-dose direct compression formulations.
• This method effectively addresses powder flow bottlenecks, improving formulation and process development.
• Offers a superior alternative to conventional methods for optimizing direct compression formulations.