Analytical method development for powder characterization: Visualization of the critical drug loading affecting the...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Characterizing particulate systems, essential for pharmaceutical manufacturing, often relies on empirical methods.
• A fundamental understanding of powder behavior, particularly flowability and tabletability, is needed for direct compression (DC) tablet production.
• Current methods lack analytical instrumentation for a deeper insight into powder dynamics.

Purpose of the Study:

• To develop a material-sparing screening approach for evaluating the impact of active pharmaceutical ingredients (APIs) on DC formulation behavior.
• To establish a method for determining the critical drug loading (CDL) at which API properties significantly alter formulation behavior.
• To enable rapid assessment of powder flowability and tabletability for manufacturability.

Main Methods:

• Analyzed flowability using a ring shear tester and tabletability via a single punch tablet press at varying compression pressures.
• Formulations with increasing amounts of model APIs were tested to assess their influence on powder properties.
• Developed a visual presentation method for simultaneous evaluation of flowability and tabletability.

Main Results:

• Flowability was found to be more sensitive to drug loading than tabletability.
• The critical drug loading is significantly influenced by the API's particulate properties, such as particle size.
• Decreasing paracetamol particle size rapidly reduced flowability but did not affect tabletability.

Conclusions:

• The developed screening approach effectively estimates the critical drug loading for DC formulations.
• API particulate properties are key determinants of formulation flowability and manufacturability.
• This method aids in optimizing DC formulations by predicting the impact of APIs on powder behavior.