A sampling system for flowing powders based on the theory of sampling

Area of Science:

• Pharmaceutical Engineering
• Analytical Chemistry
• Process Analytical Technology (PAT)

Background:

• Accurate monitoring of drug concentration in pharmaceutical powders is crucial for quality control.
• Traditional sampling methods can be time-consuming and may not be representative of the bulk material.
• The Theory of Sampling (TOS) provides a framework for developing effective sampling strategies.

Purpose of the Study:

• To develop and validate an innovative chute and stream sampler system for representative sampling of flowing powders.
• To integrate the sampling system with near-infrared (NIR) spectroscopy for real-time drug concentration determination.
• To assess the system's performance using pharmaceutical powder blends and compare it with a reference method.

Main Methods:

• Development of a three-part sampling system: chute, stream sampler, and sample collection port.
• Application of NIR spectroscopy at the chute and within the stream sampler to obtain spectral data.
• Analysis of collected samples using ultraviolet-visible (UV-Vis) spectroscopy as a reference method.
• Testing with eight pharmaceutical powder blends containing caffeine (10.5–19.5% w/w).
• Characterization of material flow properties to determine system throughput (30–35 kg/h).
• Variographic analysis to estimate analytical and sampling errors.

Main Results:

• Effective determination of drug concentration at both the chute and stream sampler locations.
• NIR calibration models demonstrated low root mean squared errors of prediction (0.65% w/w at chute, 0.51% w/w at stream sampler).
• Low bias values were observed for NIR models (-0.36% w/w at chute, 0.057% w/w at stream sampler).
• Significant agreement between NIR and UV-Vis methods, indicating high accuracy.
• Variographic analysis revealed low analytical errors (0.103% w/w² at chute, 0.181% w/w² at stream sampler) and a minimum practical error around 0.2% w/w².

Conclusions:

• The developed chute and stream sampler system, coupled with NIR spectroscopy, provides an effective and accurate method for monitoring drug concentration in flowing pharmaceutical powders.
• The system adheres to the principles of the Theory of Sampling (TOS), ensuring representative sampling.
• The validated method offers a reliable, non-destructive alternative to traditional destructive testing, enhancing process analytical technology (PAT) in pharmaceutical manufacturing.