Cohesive, multicomponent, dense powder flow characterization by NIR

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Process Engineering

Background:

• Non-aerated powder flow is critical in pharmaceutical manufacturing, impacting final product quality.
• Powder agglomeration or segregation during flow can compromise solid oral dosage forms.
• Developing in-line monitoring for powder flow characteristics is essential for process control.

Purpose of the Study:

• To develop a Process Analytical Technology (PAT) method for in-line powder flow characterization.
• To utilize near-infrared spectroscopy (NIR) for real-time analysis of pharmaceutical powder blends.
• To quantitatively determine the active pharmaceutical ingredient (API) level in flowing powder formulations.

Main Methods:

• Assembled a bench-scale hopper system to monitor powder flow.
• Employed an in-line commercial NIR spectrometer and probe for spectral data collection.
• Developed a partial least squares (PLS) chemometric model using laboratory-prepared samples.

Main Results:

• Achieved high reproducibility for static and flowing pure mannitol spectra.
• The PLS model demonstrated a low standard error of calibration (2.95% of API level) and high R2 (0.991).
• API estimates from flowing blend spectra were statistically acceptable and consistent with model predictions.

Conclusions:

• The developed NIR-based PAT method is promising for in-line powder flow characterization.
• The method accurately quantifies API levels in flowing pharmaceutical blends.
• Further improvements could lead to the adoption of this PAT tool at a production scale.