Development of a continuous direct compression platform for low-dose drug products

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• Continuous direct compression (CDC) offers advantages for pharmaceutical manufacturing.
• Low-dosed drug products present unique challenges in blend uniformity due to API quantity.
• Cohesive and agglomerated Active Pharmaceutical Ingredients (APIs) exacerbate uniformity issues in CDC.

Purpose of the Study:

• To develop and optimize a continuous direct compression process for low-dosed drug products.
• To address macroscopic and microscopic blend uniformity challenges with cohesive APIs.
• To investigate and enhance the performance of the GEA CDC-50 system.

Main Methods:

• Systematic investigation of each unit operation in the GEA CDC-50 system.
• Evaluation of material properties (density, compressibility, flow) at the feeding stage.
• Analysis of impeller configuration and speed effects on blending and residence time distribution.

Main Results:

• Feeding performance was regulated by screw speed and powder flow.
• Initial impeller design filtered feeding variability but caused micro-agglomerates.
• An optimized impeller configuration with centered blades maximized strain and shear, achieving excellent macroscopic and microscopic blend uniformity.
• The optimized process demonstrated robustness towards feeding disturbances and variable blend properties.

Conclusions:

• Optimized continuous direct compression is feasible for challenging low-dosed drug products.
• Impeller design is critical for achieving blend uniformity and tablet quality in CDC.
• Attention to lubrication is essential for successful CDC process design and execution.