Real-time quantification of low-dose cohesive formulations within a sampling interface for flowing powders

Area of Science:

• Pharmaceutical Science
• Chemical Engineering
• Process Analytical Technology (PAT)

Background:

• Cohesive powder formulations pose challenges for uniform sampling due to poor flow properties.
• Accurate monitoring of drug concentration is critical for ensuring pharmaceutical product quality and efficacy.

Purpose of the Study:

• To evaluate a novel sampling interface for cohesive powder formulations.
• To assess the performance of near-infrared (NIR) spectroscopy in quantifying drug concentrations within the sampler.
• To investigate the impact of powder properties on sampling accuracy.

Main Methods:

• Utilized a sampling interface with cohesive powders (Hausner's Ratio > 1.5, Carr's Index > 35%).
• Integrated near-infrared (NIR) spectroscopy for real-time ibuprofen concentration monitoring (1.5–4.5% w/w).
• Employed variographic analysis to assess sampling errors and blend uniformity.

Main Results:

• The sampling interface ensured continuous powder flow without agglomeration or segregation for a 6 kg blend.
• Optimized NIR calibration model achieved prediction errors and bias below 0.1% w/w.
• Variographic analysis indicated sampling errors below 0.011 (%w/w)² for low drug concentrations.

Conclusions:

• The sampling device provides statistically robust blend uniformity evaluation for cohesive powders.
• Accurate drug quantification is achievable without negatively impacting powder flow properties.
• This technology enhances confidence in the quality control of cohesive powder formulations.