AAPS PharmSciTech

, Volume 12, Issue 4, pp 1050–1055 | Cite as

Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

  • Lipika Chablani
  • Michael K. Taylor
  • Amit Mehrotra
  • Patrick Rameas
  • William C. Stagner
Research Article


The purpose of this research was to use inline real-time near-infrared (NIR) to measure the moisture content of granules manufactured using a commercial production scale continuous twin-screw granulator fluid-bed dryer milling process. A central composite response surface statistical design was used to study the effect of inlet air temperature and dew point on granule moisture content. The NIR moisture content was compared to Karl Fischer (KF) and loss on drying (LOD) moisture determinations. Using multivariate analysis, the data showed a statistically significant correlation between the conventional methods and NIR. The R 2 values for predicted moisture content by NIR versus KF and predicted moisture values by NIR versus LOD were 0.94 (p < 0.00001) and 0.85 (p < 0.0002), respectively. The adjusted R 2 for KF versus LOD correlation was 0.85 (p < 0.0001). Analysis of the response surface design data showed that inlet air temperature over a range of 35–55°C had a significant linear impact on granule moisture content as measured by predicted NIR (adjusted R 2 = 0.84, p < 0.02), KF (adjusted R 2 = 0.91, p < 0.0001), and LOD (adjusted R 2 = 0.85, p < 0.0006). The inlet air dew point range of 10–20°C did not have a significant impact on any of the moisture measurements.

Key words

continuous granulation–drying–milling near-infrared (NIR) spectroscopy process analytical technology (PAT) real-time moisture determination 



We appreciate the generous support of GlaxoSmithKline (GSK). We also appreciate the support of Mr. Scott Staton, operation and formulation manager at Campbell University Pharmaceutical Sciences Institute for editing the flow diagram of ConsiGma™ kit provided by GSK (Zebulon).


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Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Lipika Chablani
    • 1
    • 2
  • Michael K. Taylor
    • 3
  • Amit Mehrotra
    • 4
  • Patrick Rameas
    • 5
  • William C. Stagner
    • 1
  1. 1.College of Pharmacy and Health Sciences, Department of Pharmaceutical SciencesCampbell UniversityBuies CreekUSA
  2. 2.College of Pharmacy and Health SciencesGraduate Program Mercer UniversityAtlantaUSA
  3. 3.BioDelivery SciencesRaleighUSA
  4. 4.Pharma Launch and Global SupplyGlaxoSmithKlineZebulonUSA
  5. 5.Pharmaceutical DevelopmentGlaxoSmithKlineResearch Triangle ParkUSA

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