Verification of model development technique for NIR-based real-time monitoring of ingredient concentration during blending.
There has been a considerable research on the process analytical technology (PAT) and real-time monitoring based on NIR, but the model development is still an important issue and persons in charge have difficulty in building good models. In this study, to realize efficient NIR-based real-time monitoring of ingredient concentration and establish a model development method, we investigated the effect of a calibration set, spectral preprocessing, wavelengths, and other factors on the prediction error through pilot and commercial scale blending experiments. The results confirmed that the small prediction error was realized by a calibration set, including dynamic measurement spectra acquired with the target blender. In addition, the results demonstrated that locally weighted partial least squares (LW-PLS) achieved the smaller prediction error than conventional PLS. The present study has also clarified that spectral preprocessing methods and wavelengths selected to build a model affect the prediction error of ingredient concentration interactively. A wide wavelength range should be selected when the spectral preprocessing does not lessen the effect of baseline variation, while a narrow wavelength range should be selected when it strongly decreases the effect.
Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Kanagawa, Japan. Electronic address: nakagawa.hiroshi.w5@daiichisankyo.co.jp.
Hiroshi
H
Nakagawa
Department of Systems Science, Kyoto University, Kyoto, Japan.
Manabu
M
Kano
Department of Chemical Engineering, Kyoto University, Kyoto, Japan.
Shinji
S
Hasebe
Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Kanagawa, Japan.
Takuya
T
Miyano
Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Kanagawa, Japan.
Tomoyuki
T
Watanabe
Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Kanagawa, Japan.
Naoki
N
Wakiyama
D000465:Algorithms; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D004867:Equipment Design; D016018:Least-Squares Analysis; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D010602:Pharmacopoeias as Topic; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data
D004364:Pharmaceutical Preparations
Blending process; Locally weighted partial least squares (LW-PLS); Near infrared (NIR); Process analytical technology (PAT); Real-time monitoring