Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy

Aditya U. Vanarase, Manel Alcalà, Jackeline I. Jerez Rozo, Fernando J. Muzzio, Rodolfo J. Romañach

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188 Citations (Scopus)


A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration on the blends produced with a continuous mixer. The NIR method was developed for concentrations ranging from 0 to 15% (w/w) of acetaminophen (APAP), the active pharmaceutical ingredient used in the experiments. The calibration model's overall accuracy was 0.41% (w/w), and estimated through the root mean square error of cross validation (RMSECV) for samples predicted using leave-class-out cross validation. In this cross validation, each concentration was defined as a class, and when a sample of a specific concentration was predicted all samples of that concentration were left out of the calibration model. The precision of the calibration model was also estimated at various concentration levels, to facilitate the differentiation between the variation in drug concentration due to the analytical method's measurement uncertainty and the variation in the drug distribution throughout the powder blend. The results obtained are very promising since in three of the five powder mixes, the variation in the drug concentration in the powder blends was similar to that of the analytical method indicating a high degree of blend homogeneity. © 2010 Elsevier Ltd.
Original languageEnglish
Pages (from-to)5728-5733
JournalChemical Engineering Science
Issue number21
Publication statusPublished - 1 Nov 2010


  • Chemical analysis
  • Mixing
  • Near infrared spectroscopy
  • Particulate processes
  • Pharmaceuticals
  • Powders


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