A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of Sampling. Two Near-Infrared (NIR) spectroscopic calibration models were developed with powder blends that varied from 0.52 to 2.52% w/w and 1.51–4.52% w/w. The calibration models were able to determine caffeine concentration in test set blends with root mean square error of predictions and bias below 0.1% w/w. Samples were collected from the sampler device and analyzed by ultraviolet-visible (UV–Vis) to determine the caffeine concentration. A high agreement between the in-line NIR predictions and the sampled UV–Vis results was found. The paddle wheel speed in the sampler can be varied up to ±10% without affecting NIR predictions; however, the models did not respond adequately to a 25% increase in this speed. Variographic analysis showed that the sampler device may quantify low drug concentrations with nugget effects below 0.0050 (%w/w)2. This study demonstrate that the sampler device may handle throughputs up to 45 kg/h, without significantly affecting the physical properties of powder blends.

• University of Puerto Rico at Mayagüez

• PAT
• Oral solid dose

1. Acceptance value
2. blend uniformity
3. Low drug concentration
4. Near-infrared spectroscopy
5. oral solid dose
6. pat
7. Process analytical technology
8. Research Article
9. Uniformity of dosage units / Theory of Sampling (TOS)