In-line monitoring of the drug content of powder mixtures and tablets by near-infrared spectroscopy during the continuous direct compression tableting process

Kristiina Järvinen (Corresponding Author), Wolfgang Hoehe, Maiju Järvinen, Sami Poutiainen, Mikko Juuti, Sven Borchert

Research output: Contribution to journalArticleScientificpeer-review

63 Citations (Scopus)


Continuous manufacturing methods offer economic and quality advantages when compared with batch manufacturing methods. In continuous manufacturing, one requires real time assurance of quality of product via the implementation of PAT tools. This study focuses on an in-line near-infrared (NIR) spectroscopic method for determining the drug content of powder mixtures and tablets during a continuous tableting process. Tablets consisting of acetaminophen (20–30%), lactose (69.07–78.93%) and magnesium stearate (0.93–1.07%) were prepared in a continuous direct compression line that consisted of two loss-in-weight feeders, one for acetaminophen and one for premixed lactose and magnesium stearate, and a continuous mixer followed by a rotary tablet press. NIR spectroscopy was applied to the continuous mixer and tablet press to perform a 100% product check at full tableting speed. The UV-spectrophotometric method was used as an off-line reference method to determine the acetaminophen content in the samples. The powder mixture and tablet samples were taken during the process for the calibration of continuous mixer and tablet press, respectively. For the continuous mixer, model creation with the PLS method yielded R-Square and RMSEC (root mean square error of calibration) values of 0.975% and 0.56%, respectively. For the tablet press, the corresponding R-Square and RMSEC values were 0.943% and 0.75%, respectively. A test run demonstrated good predictability in the estimation of the API content in the powder mixtures and tablets during the continuous tableting process. For the continuous mixer and tablet press, the RMSEP (root mean square error of prediction) values were 0.96% and 1.37%, respectively. This study demonstrates that an NIR instrument capable of fast spectra acquisition can be a valuable tool for the in-line monitoring of the continuous mixing and tableting processes.
Original languageEnglish
Pages (from-to)680-688
JournalEuropean Journal of Pharmaceutical Sciences
Issue number4
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed



  • continuous tablet manufacturing
  • in-line process analytical technology
  • multivariate analysis
  • near infrared spectroscopy
  • quantification

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