Sample Mass Estimate for the Use of Near-Infrared and Raman Spectroscopy to Monitor Content Uniformity in a Tablet Press Feed Frame of a Drug Product Continuous Manufacturing Process.

ABSTRACT

Recently, feed frame-based process analytical technology measurements used to assure product quality during continuous manufacturing processes have received significant attention. These measurements are able to accurately determine uniformity of the powder blend before compression, and in these applications, it is necessary to understand the interrogated sample volume per measurement. This understanding ensures that the blend measurement can be indicative of the uniformity of the final dosage form. A scientifically sound approach is proposed here to estimate sample mass for a continuous manufacturing process that utilizes either near infrared or Raman spectroscopy. A wide range of commercially available probes with varying spot diameters are considered. By comparing near infrared and Raman spectroscopy, an optimal range of probe spot diameters was identified in order to reach an estimated sample mass between 50 and 500 mg for pharmaceutical blends per measurement, which is equivalent to common tablet weight ranges for solid oral dosage forms currently on the market.