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In-line temperature measurement to improve the understanding of the wetting phase in twin-screw wet granulation and its use in process development.
Int J Pharm. 2020 Jun 30; 584:119451.IJ

Abstract

Wetting is the initial stage of wet granulation processes during which the first contact between the powder and the liquid occurs. Wetting is a critical step to allow granule growth and consolidation, but also to ensure uniform active pharmaceutical ingredient (API) distribution over all granule size fractions. A physical understanding of the wetting stage is therefore crucial to design a robust granulation process. In twin-screw granulation, wetting is physically separated from granule consolidation, growth, breakage and attrition. The present study used this particularity to investigate the wetting step in such a way that the fundamental mechanisms governing the wetting can be linked and understood. A modified granulator barrel was used allowing the collection of granules immediately after the wetting. A low drug-loaded pharmaceutical formulation containing a poorly soluble and poorly wettable API was used for this investigation. Granules obtained after the wetting zone were analysed for granule size distribution, API distribution over the different size fractions and granule temperature. It was found that "wetting efficiency" (i.e., fraction of powder being nucleated during the wetting stage) could be predicted using an energy balance based on in-line measurement of the granule temperature. Wetting efficiency could moreover be linked to final granule quality attributes (i.e., granule size distribution) at the outlet of the granulator. It was further demonstrated that granule growth and consolidation could only be achieved when complete wetting was achieved in the wetting zone of the granulator. This study suggested a methodology based on in-line temperature measurements to quickly determine wetting efficiency. The described methodology could therefore be used as a tool to gain more fundamental understanding of the wetting stage during twin-screw granulation as well as to define suitable formulation and process ranges for further granulation process development.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.Laboratory of Pharmaceutical Process Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.BIOMATH - Department of Mathematical Modelling, Statistics and Bio-informatics, Ghent University, Coupure Links 653, Ghent, Belgium.Chemical & Pharmaceutical Development, Pharma R&D, Bayer AG, Friedrich-Ebert-Straβe 475 42117, Wuppertal, Germany.Chemical & Pharmaceutical Development, Pharma R&D, Bayer AG, Friedrich-Ebert-Straβe 475 42117, Wuppertal, Germany.Laboratory of Pharmaceutical Process Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.BIOMATH - Department of Mathematical Modelling, Statistics and Bio-informatics, Ghent University, Coupure Links 653, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. Electronic address: Thomas.DeBeer@UGent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32454132

Citation

Stauffer, F, et al. "In-line Temperature Measurement to Improve the Understanding of the Wetting Phase in Twin-screw Wet Granulation and Its Use in Process Development." International Journal of Pharmaceutics, vol. 584, 2020, p. 119451.
Stauffer F, Ryckaert A, Vanhoorne V, et al. In-line temperature measurement to improve the understanding of the wetting phase in twin-screw wet granulation and its use in process development. Int J Pharm. 2020;584:119451.
Stauffer, F., Ryckaert, A., Vanhoorne, V., Van Hauwermeiren, D., Funke, A., Djuric, D., Vervaet, C., Nopens, I., & De Beer, T. (2020). In-line temperature measurement to improve the understanding of the wetting phase in twin-screw wet granulation and its use in process development. International Journal of Pharmaceutics, 584, 119451. https://doi.org/10.1016/j.ijpharm.2020.119451
Stauffer F, et al. In-line Temperature Measurement to Improve the Understanding of the Wetting Phase in Twin-screw Wet Granulation and Its Use in Process Development. Int J Pharm. 2020 Jun 30;584:119451. PubMed PMID: 32454132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In-line temperature measurement to improve the understanding of the wetting phase in twin-screw wet granulation and its use in process development. AU - Stauffer,F, AU - Ryckaert,A, AU - Vanhoorne,V, AU - Van Hauwermeiren,D, AU - Funke,Adrian, AU - Djuric,Dejan, AU - Vervaet,C, AU - Nopens,I, AU - De Beer,T, Y1 - 2020/05/23/ PY - 2020/04/14/received PY - 2020/05/18/revised PY - 2020/05/19/accepted PY - 2020/5/27/pubmed PY - 2021/2/24/medline PY - 2020/5/27/entrez KW - Continuous manufacturing KW - Heat transfer KW - Nucleation KW - Pharmaceutical KW - Thermal imaging KW - Twin-screw granulation SP - 119451 EP - 119451 JF - International journal of pharmaceutics JO - Int J Pharm VL - 584 N2 - Wetting is the initial stage of wet granulation processes during which the first contact between the powder and the liquid occurs. Wetting is a critical step to allow granule growth and consolidation, but also to ensure uniform active pharmaceutical ingredient (API) distribution over all granule size fractions. A physical understanding of the wetting stage is therefore crucial to design a robust granulation process. In twin-screw granulation, wetting is physically separated from granule consolidation, growth, breakage and attrition. The present study used this particularity to investigate the wetting step in such a way that the fundamental mechanisms governing the wetting can be linked and understood. A modified granulator barrel was used allowing the collection of granules immediately after the wetting. A low drug-loaded pharmaceutical formulation containing a poorly soluble and poorly wettable API was used for this investigation. Granules obtained after the wetting zone were analysed for granule size distribution, API distribution over the different size fractions and granule temperature. It was found that "wetting efficiency" (i.e., fraction of powder being nucleated during the wetting stage) could be predicted using an energy balance based on in-line measurement of the granule temperature. Wetting efficiency could moreover be linked to final granule quality attributes (i.e., granule size distribution) at the outlet of the granulator. It was further demonstrated that granule growth and consolidation could only be achieved when complete wetting was achieved in the wetting zone of the granulator. This study suggested a methodology based on in-line temperature measurements to quickly determine wetting efficiency. The described methodology could therefore be used as a tool to gain more fundamental understanding of the wetting stage during twin-screw granulation as well as to define suitable formulation and process ranges for further granulation process development. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/32454132/In_line_temperature_measurement_to_improve_the_understanding_of_the_wetting_phase_in_twin_screw_wet_granulation_and_its_use_in_process_development_ DB - PRIME DP - Unbound Medicine ER -