Terahertz in‐line sensor for direct coating thickness measurement of individual tablets during film coating in real‐time

Robert K. May, Michael J. Evans, Shuncong Zhong, Ian Warr, Lynn F. Gladden, Yaochun Shen, J. Axel Zeitler

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.
LanguageEnglish
Pages1535-1544
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number4
Early online date18 Oct 2010
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Tablets
Terahertz Imaging
Technology
Dosage Forms
Quality Control
Pharmaceutical Preparations
Calibration
Weight Gain

Keywords

  • coating
  • unit operations
  • formulation
  • coating thickness
  • terahertz pulsed imaging
  • in-line sensor
  • quality by design
  • process analytical technology

Cite this

May, Robert K. ; Evans, Michael J. ; Zhong, Shuncong ; Warr, Ian ; Gladden, Lynn F. ; Shen, Yaochun ; Zeitler, J. Axel . / Terahertz in‐line sensor for direct coating thickness measurement of individual tablets during film coating in real‐time. In: Journal of Pharmaceutical Sciences. 2011 ; Vol. 100, No. 4. pp. 1535-1544.
@article{0cc44d8b25954f14b43df7a9b756badd,
title = "Terahertz in‐line sensor for direct coating thickness measurement of individual tablets during film coating in real‐time",
abstract = "We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.",
keywords = "coating, unit operations, formulation, coating thickness, terahertz pulsed imaging, in-line sensor, quality by design, process analytical technology",
author = "May, {Robert K.} and Evans, {Michael J.} and Shuncong Zhong and Ian Warr and Gladden, {Lynn F.} and Yaochun Shen and Zeitler, {J. Axel}",
year = "2011",
month = "4",
doi = "10.1002/jps.22359",
language = "English",
volume = "100",
pages = "1535--1544",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
number = "4",

}

Terahertz in‐line sensor for direct coating thickness measurement of individual tablets during film coating in real‐time. / May, Robert K.; Evans, Michael J.; Zhong, Shuncong; Warr, Ian; Gladden, Lynn F.; Shen, Yaochun; Zeitler, J. Axel .

In: Journal of Pharmaceutical Sciences, Vol. 100, No. 4, 04.2011, p. 1535-1544.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Terahertz in‐line sensor for direct coating thickness measurement of individual tablets during film coating in real‐time

AU - May, Robert K.

AU - Evans, Michael J.

AU - Zhong, Shuncong

AU - Warr, Ian

AU - Gladden, Lynn F.

AU - Shen, Yaochun

AU - Zeitler, J. Axel

PY - 2011/4

Y1 - 2011/4

N2 - We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.

AB - We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.

KW - coating

KW - unit operations

KW - formulation

KW - coating thickness

KW - terahertz pulsed imaging

KW - in-line sensor

KW - quality by design

KW - process analytical technology

U2 - 10.1002/jps.22359

DO - 10.1002/jps.22359

M3 - Article

VL - 100

SP - 1535

EP - 1544

JO - Journal of Pharmaceutical Sciences

T2 - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 4

ER -