Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography

Daniel Markl, Manuel Zettl, Günther Hannesschläger, Stephan Sacher, Michael Leitner, Andreas Buchsbaum, Johannes G. Khinast

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The paper presents a new in-line measurement technique for determining the coating thickness and uniformity of pharmaceutical pellets during film-coating in a fluid-bed apparatus. Non-destructive and contact-free process monitoring was performed via an optical coherence tomography (OCT) sensor providing cross-section images. Through the OCT measurements, the coating thickness could be determined directly, without a chemometric calibration model required for the quantification. The direct integration of the OCT sensor head into the fluid-bed systems allowed continuous monitoring of the coating growth. Moreover, the in-line investigation of the intra- and inter-pellet coating uniformity was possible due to OCT's high acquisition rate. Results of the in-line OCT measurements were validated using both off-line OCT images and particle size analysis by performing an image analysis of samples that were periodically removed from the process during the production. Three batches were produced under the same process conditions demonstrating the reproducibility of the results. Rather than providing the temporal and spatial average of a large number of pellets, the OCT sensor characterized local pellet properties of up to 130 individual pellets per minute. Therefore, the OCT technology allows the operator to directly monitor the coating thickness and uniformity in sub-micron resolution, which makes it a promising in-line PAT method.

LanguageEnglish
Pages200-208
Number of pages9
JournalChemical Engineering Science
Volume125
Early online date3 Jun 2014
DOIs
Publication statusPublished - 24 Mar 2015

Fingerprint

Optical tomography
Optical Coherence Tomography
Calibration
Coatings
Monitoring
Sensors
Fluids
Process monitoring
Particle Size
Reproducibility of Results
Particle size analysis
Contacts (fluid mechanics)
Drug products
Image analysis
Head
Technology
Growth
Pharmaceutical Preparations

Keywords

  • in-line quality control
  • optical coherence tomography
  • pharmaceutical film-coated pellets
  • process analytical technology

Cite this

Markl, D., Zettl, M., Hannesschläger, G., Sacher, S., Leitner, M., Buchsbaum, A., & Khinast, J. G. (2015). Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography. Chemical Engineering Science, 125, 200-208. https://doi.org/10.1016/j.ces.2014.05.049
Markl, Daniel ; Zettl, Manuel ; Hannesschläger, Günther ; Sacher, Stephan ; Leitner, Michael ; Buchsbaum, Andreas ; Khinast, Johannes G. / Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography. In: Chemical Engineering Science. 2015 ; Vol. 125. pp. 200-208.
@article{87dfa70e34b64285a84d4eefb6cfee34,
title = "Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography",
abstract = "The paper presents a new in-line measurement technique for determining the coating thickness and uniformity of pharmaceutical pellets during film-coating in a fluid-bed apparatus. Non-destructive and contact-free process monitoring was performed via an optical coherence tomography (OCT) sensor providing cross-section images. Through the OCT measurements, the coating thickness could be determined directly, without a chemometric calibration model required for the quantification. The direct integration of the OCT sensor head into the fluid-bed systems allowed continuous monitoring of the coating growth. Moreover, the in-line investigation of the intra- and inter-pellet coating uniformity was possible due to OCT's high acquisition rate. Results of the in-line OCT measurements were validated using both off-line OCT images and particle size analysis by performing an image analysis of samples that were periodically removed from the process during the production. Three batches were produced under the same process conditions demonstrating the reproducibility of the results. Rather than providing the temporal and spatial average of a large number of pellets, the OCT sensor characterized local pellet properties of up to 130 individual pellets per minute. Therefore, the OCT technology allows the operator to directly monitor the coating thickness and uniformity in sub-micron resolution, which makes it a promising in-line PAT method.",
keywords = "in-line quality control, optical coherence tomography, pharmaceutical film-coated pellets, process analytical technology",
author = "Daniel Markl and Manuel Zettl and G{\"u}nther Hannesschl{\"a}ger and Stephan Sacher and Michael Leitner and Andreas Buchsbaum and Khinast, {Johannes G.}",
year = "2015",
month = "3",
day = "24",
doi = "10.1016/j.ces.2014.05.049",
language = "English",
volume = "125",
pages = "200--208",
journal = "Chemical Engineering Science",
issn = "0009-2509",

}

Markl, D, Zettl, M, Hannesschläger, G, Sacher, S, Leitner, M, Buchsbaum, A & Khinast, JG 2015, 'Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography' Chemical Engineering Science, vol. 125, pp. 200-208. https://doi.org/10.1016/j.ces.2014.05.049

Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography. / Markl, Daniel; Zettl, Manuel; Hannesschläger, Günther; Sacher, Stephan; Leitner, Michael; Buchsbaum, Andreas; Khinast, Johannes G.

In: Chemical Engineering Science, Vol. 125, 24.03.2015, p. 200-208.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Calibration-free in-line monitoring of pellet coating processes via optical coherence tomography

AU - Markl, Daniel

AU - Zettl, Manuel

AU - Hannesschläger, Günther

AU - Sacher, Stephan

AU - Leitner, Michael

AU - Buchsbaum, Andreas

AU - Khinast, Johannes G.

PY - 2015/3/24

Y1 - 2015/3/24

N2 - The paper presents a new in-line measurement technique for determining the coating thickness and uniformity of pharmaceutical pellets during film-coating in a fluid-bed apparatus. Non-destructive and contact-free process monitoring was performed via an optical coherence tomography (OCT) sensor providing cross-section images. Through the OCT measurements, the coating thickness could be determined directly, without a chemometric calibration model required for the quantification. The direct integration of the OCT sensor head into the fluid-bed systems allowed continuous monitoring of the coating growth. Moreover, the in-line investigation of the intra- and inter-pellet coating uniformity was possible due to OCT's high acquisition rate. Results of the in-line OCT measurements were validated using both off-line OCT images and particle size analysis by performing an image analysis of samples that were periodically removed from the process during the production. Three batches were produced under the same process conditions demonstrating the reproducibility of the results. Rather than providing the temporal and spatial average of a large number of pellets, the OCT sensor characterized local pellet properties of up to 130 individual pellets per minute. Therefore, the OCT technology allows the operator to directly monitor the coating thickness and uniformity in sub-micron resolution, which makes it a promising in-line PAT method.

AB - The paper presents a new in-line measurement technique for determining the coating thickness and uniformity of pharmaceutical pellets during film-coating in a fluid-bed apparatus. Non-destructive and contact-free process monitoring was performed via an optical coherence tomography (OCT) sensor providing cross-section images. Through the OCT measurements, the coating thickness could be determined directly, without a chemometric calibration model required for the quantification. The direct integration of the OCT sensor head into the fluid-bed systems allowed continuous monitoring of the coating growth. Moreover, the in-line investigation of the intra- and inter-pellet coating uniformity was possible due to OCT's high acquisition rate. Results of the in-line OCT measurements were validated using both off-line OCT images and particle size analysis by performing an image analysis of samples that were periodically removed from the process during the production. Three batches were produced under the same process conditions demonstrating the reproducibility of the results. Rather than providing the temporal and spatial average of a large number of pellets, the OCT sensor characterized local pellet properties of up to 130 individual pellets per minute. Therefore, the OCT technology allows the operator to directly monitor the coating thickness and uniformity in sub-micron resolution, which makes it a promising in-line PAT method.

KW - in-line quality control

KW - optical coherence tomography

KW - pharmaceutical film-coated pellets

KW - process analytical technology

UR - http://www.scopus.com/inward/record.url?scp=85028130329&partnerID=8YFLogxK

U2 - 10.1016/j.ces.2014.05.049

DO - 10.1016/j.ces.2014.05.049

M3 - Article

VL - 125

SP - 200

EP - 208

JO - Chemical Engineering Science

T2 - Chemical Engineering Science

JF - Chemical Engineering Science

SN - 0009-2509

ER -