Microdynamic flowability for early API characterisation: A case study on Palbociclib.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Early characterisation of active pharmaceutical ingredients (APIs) is crucial due to compound scarcity and cost.
• Understanding powder flowability is essential for successful formulation development and process design.
• Micronisation can improve drug dissolution but may negatively impact powder flow properties.

Purpose of the Study:

• To introduce microdynamic flowability as an innovative method for early API characterisation.
• To investigate the effect of laboratory-scale micronisation on the flowability of Palbociclib.
• To quantitatively describe powder agglomeration using minimal sample quantities.

Main Methods:

• Utilisation of microdynamic flow measurements during the pre-formulation stage.
• Laboratory-scale micronisation of a poorly water-soluble drug (Palbociclib).
• Image analysis for quantitative description of agglomeration with <200 mg samples.

Main Results:

• Micronisation of Palbociclib enhanced dissolution but adversely affected its flowability.
• Cohesive forces leading to agglomeration were quantitatively described for the first time using image analysis.
• Microdynamic flow studies provided critical insights into API processability under low-stress conditions.

Conclusions:

• Microdynamic flow studies offer valuable insights into API processability, especially under research and development (R&D) conditions.
• Advanced flowability analysis in early development improves understanding and control of powder processing.
• This approach supports strategic decision-making in pharmaceutical manufacturing and particle engineering.