Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices

J. T. T. Leskinen (Corresponding Author), Matti-Antero Okkonen, Maunu Toiviainen, S. Poutiainen, Mari Tenhunen, Pekka Teppola, R. Lappalainen, J. Ketolainen, K. Järvinen

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

Abstract

Fluidized bed granulation is a common size enlargement process in the pharmaceutical industry, in which fine powder is agglomerated using a liquid binder to obtain larger granules. However, fluidized bed granulation is a complex process by nature, being difficult to control due to the strong interactions between many process variables, such as moisture content and granule size. In order to control the process via correct pathway, one should be able to monitor the process, i.e. measure the process variables in-line.

In this study, three Process Analytical Technology (PAT) devices, i.e. an acoustic emission sensor, a flash topography particle size analyzer and multi-point NIR probes, were developed and instrumented into a labscale fluidized bed granulator for simultaneous granulation process monitoring. Parallel techniques were used for characterizing the granule size distribution and moisture content of granules during fluidization. CelletsR, protease granules and caffeine formulation were used as samples. Granulation was carried out in a custom made modular top spray granulation chamber.

The granule size values obtained with the acoustic emission and flash topography particle size analyzer were in good agreement with the values measured with offline reference methods. Multi-point NIR (eight probes) and acoustic emission methods were able to detect the three granulation phases, mixing, agglomeration and drying. Single location monitoring does not reflect the heterogeneous sample during granulation, and thus, more information can be obtained by multi-point NIR. In general, the sensitivity of the multi-point NIR technique is susceptible to the fouling of probe windows whereas the acoustic emission technique is sensitive to background fluidizing air flows as well as external interference. The most informative data can be obtained when multiple PAT techniques are applied simultaneously for in-line process monitoring.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalChemical Engineering Journal
Volume164
Issue number2-3
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed
Event9th International Symposium on Agglomeration and 4th International Granulation Workshop - Sheffield, United Kingdom
Duration: 24 Jun 200926 Jun 2009

Fingerprint

Granulators
Granulation
acoustic emission
Process monitoring
Fluidized beds
Acoustic emissions
probe
monitoring
moisture content
particle size
topography
Fluidization
pharmaceutical industry
fluidization
Topography
agglomeration
fouling
spray
airflow
Moisture

Keywords

  • Fluid bed
  • granulation
  • particle size
  • PAT

Cite this

Leskinen, J. T. T., Okkonen, M-A., Toiviainen, M., Poutiainen, S., Tenhunen, M., Teppola, P., ... Järvinen, K. (2010). Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices. Chemical Engineering Journal, 164(2-3), 268-274. https://doi.org/10.1016/j.cej.2010.08.064
Leskinen, J. T. T. ; Okkonen, Matti-Antero ; Toiviainen, Maunu ; Poutiainen, S. ; Tenhunen, Mari ; Teppola, Pekka ; Lappalainen, R. ; Ketolainen, J. ; Järvinen, K. / Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices. In: Chemical Engineering Journal. 2010 ; Vol. 164, No. 2-3. pp. 268-274.
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Leskinen, JTT, Okkonen, M-A, Toiviainen, M, Poutiainen, S, Tenhunen, M, Teppola, P, Lappalainen, R, Ketolainen, J & Järvinen, K 2010, 'Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices', Chemical Engineering Journal, vol. 164, no. 2-3, pp. 268-274. https://doi.org/10.1016/j.cej.2010.08.064

Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices. / Leskinen, J. T. T. (Corresponding Author); Okkonen, Matti-Antero; Toiviainen, Maunu; Poutiainen, S.; Tenhunen, Mari; Teppola, Pekka; Lappalainen, R.; Ketolainen, J.; Järvinen, K.

In: Chemical Engineering Journal, Vol. 164, No. 2-3, 2010, p. 268-274.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices

AU - Leskinen, J. T. T.

AU - Okkonen, Matti-Antero

AU - Toiviainen, Maunu

AU - Poutiainen, S.

AU - Tenhunen, Mari

AU - Teppola, Pekka

AU - Lappalainen, R.

AU - Ketolainen, J.

AU - Järvinen, K.

PY - 2010

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N2 - Fluidized bed granulation is a common size enlargement process in the pharmaceutical industry, in which fine powder is agglomerated using a liquid binder to obtain larger granules. However, fluidized bed granulation is a complex process by nature, being difficult to control due to the strong interactions between many process variables, such as moisture content and granule size. In order to control the process via correct pathway, one should be able to monitor the process, i.e. measure the process variables in-line.In this study, three Process Analytical Technology (PAT) devices, i.e. an acoustic emission sensor, a flash topography particle size analyzer and multi-point NIR probes, were developed and instrumented into a labscale fluidized bed granulator for simultaneous granulation process monitoring. Parallel techniques were used for characterizing the granule size distribution and moisture content of granules during fluidization. CelletsR, protease granules and caffeine formulation were used as samples. Granulation was carried out in a custom made modular top spray granulation chamber.The granule size values obtained with the acoustic emission and flash topography particle size analyzer were in good agreement with the values measured with offline reference methods. Multi-point NIR (eight probes) and acoustic emission methods were able to detect the three granulation phases, mixing, agglomeration and drying. Single location monitoring does not reflect the heterogeneous sample during granulation, and thus, more information can be obtained by multi-point NIR. In general, the sensitivity of the multi-point NIR technique is susceptible to the fouling of probe windows whereas the acoustic emission technique is sensitive to background fluidizing air flows as well as external interference. The most informative data can be obtained when multiple PAT techniques are applied simultaneously for in-line process monitoring.

AB - Fluidized bed granulation is a common size enlargement process in the pharmaceutical industry, in which fine powder is agglomerated using a liquid binder to obtain larger granules. However, fluidized bed granulation is a complex process by nature, being difficult to control due to the strong interactions between many process variables, such as moisture content and granule size. In order to control the process via correct pathway, one should be able to monitor the process, i.e. measure the process variables in-line.In this study, three Process Analytical Technology (PAT) devices, i.e. an acoustic emission sensor, a flash topography particle size analyzer and multi-point NIR probes, were developed and instrumented into a labscale fluidized bed granulator for simultaneous granulation process monitoring. Parallel techniques were used for characterizing the granule size distribution and moisture content of granules during fluidization. CelletsR, protease granules and caffeine formulation were used as samples. Granulation was carried out in a custom made modular top spray granulation chamber.The granule size values obtained with the acoustic emission and flash topography particle size analyzer were in good agreement with the values measured with offline reference methods. Multi-point NIR (eight probes) and acoustic emission methods were able to detect the three granulation phases, mixing, agglomeration and drying. Single location monitoring does not reflect the heterogeneous sample during granulation, and thus, more information can be obtained by multi-point NIR. In general, the sensitivity of the multi-point NIR technique is susceptible to the fouling of probe windows whereas the acoustic emission technique is sensitive to background fluidizing air flows as well as external interference. The most informative data can be obtained when multiple PAT techniques are applied simultaneously for in-line process monitoring.

KW - Fluid bed

KW - granulation

KW - particle size

KW - PAT

U2 - 10.1016/j.cej.2010.08.064

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M3 - Article

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Leskinen JTT, Okkonen M-A, Toiviainen M, Poutiainen S, Tenhunen M, Teppola P et al. Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices. Chemical Engineering Journal. 2010;164(2-3):268-274. https://doi.org/10.1016/j.cej.2010.08.064