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Optimization of Critical Quality Attributes in Tablet Film Coating and Design Space Determination Using Pilot-Scale Experimental Data

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Abstract

In this study, the novel high-speed tablet film coating process in the continuous manufacturing was investigated. The influence of key process variables (inlet air flow rate, inlet air temperature, and suspension spray rate) were investigated using a Box-Behnken experimental design method. Statistical regression models were developed to predict the outlet air temperature and relative humidity, the coating efficiency, the tablet moisture content, and coating uniformity. The effects of the three key process variables were comprehensively investigated based on mathematical analysis, contour plots, and interaction plots. The results indicate that all the process responses are affected by changing the inlet air flow rate, temperature, and suspension spray rate. A design space (DS) in terms of failure probability was determined based on specifications for tablet moisture content (< 3.5%) and coating uniformity (tablet weight standard deviation < 4 mg for tablet weight of 200 mg) using Monte Carlo simulations. Independent experiments were carried out and successfully validated the robustness and accuracy of the determined DS for the investigated tablet film coating process. All the data were generated using an industrial pilot-scale novel high-speed tablet coating unit from a continuous manufacturing line. The work facilitates the quality by design implementation of continuous pharmaceutical manufacturing.

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Acknowledgments

The project is supported by Merck & Co., Inc., Kenilworth, NJ, USA. The authors would like to thank Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, for funding the project and providing the data set used in the present work. A license of software MODDE 12.0 has been provided by Sartorius Stedim Biotech.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Massachusetts Lowell, 1 University Avenue, Lowell, Massachusetts, 01854, USA

    Huolong Liu & Seongkyu Yoon

  2. Pharmaceutical Commercialization Technology, Merck & Co., Inc., Kenilworth, New Jersey, USA

    Robert Meyer, Laura Wareham, Matthew Metzger & Anthony Tantuccio

  3. Applied Mathematics and Modeling, Scientific Modeling Platforms, Merck & Co., Inc., Kenilworth, New Jersey, USA

    Matthew Flamm

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  1. Huolong Liu
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Correspondence to Seongkyu Yoon.

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Liu, H., Meyer, R., Flamm, M. et al. Optimization of Critical Quality Attributes in Tablet Film Coating and Design Space Determination Using Pilot-Scale Experimental Data. AAPS PharmSciTech 22, 17 (2021). https://doi.org/10.1208/s12249-020-01884-w

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