AAPS PharmSciTech

, Volume 19, Issue 3, pp 1243–1253 | Cite as

A Scale-up Approach for Film Coating Process Based on Surface Roughness as the Critical Quality Attribute

  • Hiroyuki Yoshino
  • Yuko Hara
  • Masafumi Dohi
  • Kazunari Yamashita
  • Tadashi Hakomori
  • Shin-ichiro Kimura
  • Yasunori Iwao
  • Shigeru Itai
Research Article


Scale-up approaches for film coating process have been established for each type of film coating equipment from thermodynamic and mechanical analyses for several decades. The objective of the present study was to establish a versatile scale-up approach for film coating process applicable to commercial production that is based on critical quality attribute (CQA) using the Quality by Design (QbD) approach and is independent of the equipment used. Experiments on a pilot scale using the Design of Experiment (DoE) approach were performed to find a suitable CQA from surface roughness, contact angle, color difference, and coating film properties by terahertz spectroscopy. Surface roughness was determined to be a suitable CQA from a quantitative appearance evaluation. When surface roughness was fixed as the CQA, the water content of the film-coated tablets was determined to be the critical material attribute (CMA), a parameter that does not depend on scale or equipment. Finally, to verify the scale-up approach determined from the pilot scale, experiments on a commercial scale were performed. The good correlation between the surface roughness (CQA) and the water content (CMA) identified at the pilot scale was also retained at the commercial scale, indicating that our proposed method should be useful as a scale-up approach for film coating process.


film coating scale-up appearance critical quality attribute critical material attribute 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Hiroyuki Yoshino
    • 1
    • 2
  • Yuko Hara
    • 1
  • Masafumi Dohi
    • 1
  • Kazunari Yamashita
    • 1
  • Tadashi Hakomori
    • 1
  • Shin-ichiro Kimura
    • 2
  • Yasunori Iwao
    • 2
  • Shigeru Itai
    • 2
  1. 1.Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc.YaizuJapan
  2. 2.Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan

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