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Evaluation and Monitoring of the API Content of a Portable Near Infrared Instrument Combined with Chemometrics Based on Fluidized Bed Mixing Process

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Abstract

Purpose

With the promulgation of industry guidelines, near infrared spectroscopy (NIRS) monitoring the uniformity of solid oral preparations has become one of the most reported studies. The purpose of the present study is to develop a near infrared (NIR) method for the in-line assessment of the active pharmaceutical ingredient (API) content in the fluidized bed mixing process, as well as to introduce a portable NIR sensor to monitor the fluidized bed production visually.

Methods

A portable NIR sensor was used to monitor the content of the API in the fluidized bed mixing process. An experimental fluidized bed was performed and the corresponding NIR spectra were collected in-line. The spectrum selection method of cosine distance for in-line spectra was performed, and four wavelength optimization methods were compared to improve the accuracy of the model.

Results

Throughout the mixing process, the content uniformity of the API was a critical quality attribute (CQA). The partial least squares regression (PLSR) quantitative model of API content was established. The results showed that the cosine distance combined with the multi-variable selection methods (CC, VIP, RATC, and UVE) could obtain more useful information than the single method. The root mean square error of cross validation (RMSECV) and root mean square error of prediction (RMSEP) values of the optimal PLSR model were 1.8588% and 1.5296%, respectively.

Conclusion

Based on the results obtained, this study could be used as a reference for the pilot of in-line monitoring of miniature NIR sensors and the connection of key process parameters to realize intelligent production of solid preparations.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors are grateful for the supply of the fluidized bed of SMA Pharmatech Co., Ltd. (Zibo, China).

Funding

This work was supported by the National Key Research and Development Program of China (2019YFC1711200), the Major Innovation Project of Shandong Province (2018CXGC1405), Fundamental Research Funds of Shandong University (2019GN092) and Future Scholar Program of Shandong University.

Author information

Author notes

  1. Kefan Zhang and Haiyan Wang these authors contributed equally to this work and should be regarded as co-first authors.

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Wenhuaxi Road 44, Jinan, 250012, China

    Kefan Zhang, Haiyan Wang, Liang Zhong, Lanling Liu, Ruiqi Huang, Hui Zhang, Lian Li & Hengchang Zang

  2. NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Cheeloo College of Medicine, Shandong University, Wenhuaxi Road 44, Jinan, 250012, China

    Hengchang Zang

  3. Shandong SMA Pharmatech Co, 165, Huabei Rd., High & New Technology Zone, Shandong, 0533, Ltd Zibo, China

    Dongbo Xu & Wenping Yin

  4. National Glycoengineering Research Center, Shandong University, Binhai Road 72, Qingdao, 266200, China

    Hengchang Zang

  5. Key Laboratory of Chemical Biology (Ministry of Education), Shandong University, Wenhuaxi Road 44, Jinan, 250012, China

    Hengchang Zang

Authors
  1. Kefan Zhang
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  2. Haiyan Wang
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Correspondence to Lian Li or Hengchang Zang.

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Zhang, K., Wang, H., Zhong, L. et al. Evaluation and Monitoring of the API Content of a Portable Near Infrared Instrument Combined with Chemometrics Based on Fluidized Bed Mixing Process. J Pharm Innov 17, 1136–1147 (2022). https://doi.org/10.1007/s12247-021-09581-2

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