Building the quality into pellet manufacturing environment--feasibility study and validation of an in-line quantitative near infrared (NIR) method.
The present study focuses on the implementation of an in-line quantitative near infrared (NIR) spectroscopic method for determining the active content of pharmaceutical pellets. The first aim was to non-invasively interface a dispersive NIR spectrometer with four realistic particle streams existing in the pellets manufacturing environment. Regardless of the particle stream characteristics investigated, NIR together with Principal Component Analysis (PCA) was able to classify the samples according to their active content. Further, one of these particle stream interfaces was non-invasively investigated with a FT-NIR spectrometer. A predictive model based on Partial Least Squares (PLS) regression was able to determine the active content of pharmaceutical pellets. The NIR method was finally validated with an external validation set for an API concentration range from 80 to 120% of the targeted active content. The prediction error of 0.9% (root mean standard error of prediction, RMSEP) was low, indicating the accuracy of the NIR method. The accuracy profile on the validation results, an innovative approach based on tolerance intervals, demonstrated the actual and future performance of the in-line NIR method. Accordingly, the present approach paves the way for real-time release-based quality system.
Analytical Chemistry Laboratory, CIRM, University of Liège, avenue de l'Hôpital 1, 4000 Liège, Belgium. jmantanus@ulg.ac.be
Jérôme
J
Mantanus
Eric
E
Ziémons
Eric
E
Rozet
Bruno
B
Streel
Régis
R
Klinkenberg
Brigitte
B
Evrard
Jukka
J
Rantanen
Philippe
P
Hubert
D002138:Calibration; D004304:Dosage Forms; D004345:Drug Industry / Q000379:methods*; D005240:Feasibility Studies; D016018:Least-Squares Analysis; D004364:Pharmaceutical Preparations / Q000032:analysis; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
D004304:Dosage Forms; D004364:Pharmaceutical Preparations