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Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design.
Int J Pharm. 2020 Feb 25; 576:119004.IJ

Abstract

Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically assessed the impact of different screw configurations and process settings on eight model formulations, varying in filler type, active pharmaceutical ingredient (API) characteristics and drug load. Although liquid to solid (L/S) ratio was the most influential variable for all formulations, also a large effect of the kneading element thickness was observed. Narrow kneading elements with a length to diameter ratio (L/D) of 1/6 had a significant detrimental effect on granule size, flow and strength compared to 1/4 L/D elements. The effects of kneading element distribution and barrel fill level were less pronounced. At low drug load, both filler types could be used to obtain granules with acceptable critical quality attributes (CQAs) for both APIs. Granulation at high drug load of the poorly soluble, poorly wettable API mebendazole proved challenging as it could not be processed using lactose as filler, in contrast to lactose/MCC. As formulations containing lactose/MCC as filler were less influenced by different screw configurations, process settings and API characteristics than formulations without MCC, lactose/MCC/HPMC was considered a promising platform formulation.

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Authors+Show Affiliations

Portier C
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Pandelaere K
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Delaet U
Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Vigh T
Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Di Pretoro G
Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
De Beer T
Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Vervaet C
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Vanhoorne V
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: Valerie.Vanhoorne@UGent.be.

MeSH

CelluloseDrug CompoundingExcipientsLactoseMebendazoleMetforminParticle SizeSolubilityTechnology, PharmaceuticalWettability

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

31935475

Citation

Portier, Christoph, et al. "Continuous Twin Screw Granulation: a Complex Interplay Between Formulation Properties, Process Settings and Screw Design." International Journal of Pharmaceutics, vol. 576, 2020, p. 119004.
Portier C, Pandelaere K, Delaet U, et al. Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design. Int J Pharm. 2020;576:119004.
Portier, C., Pandelaere, K., Delaet, U., Vigh, T., Di Pretoro, G., De Beer, T., Vervaet, C., & Vanhoorne, V. (2020). Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design. International Journal of Pharmaceutics, 576, 119004. https://doi.org/10.1016/j.ijpharm.2019.119004
Portier C, et al. Continuous Twin Screw Granulation: a Complex Interplay Between Formulation Properties, Process Settings and Screw Design. Int J Pharm. 2020 Feb 25;576:119004. PubMed PMID: 31935475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design. AU - Portier,Christoph, AU - Pandelaere,Kenny, AU - Delaet,Urbain, AU - Vigh,Tamas, AU - Di Pretoro,Giustino, AU - De Beer,Thomas, AU - Vervaet,Chris, AU - Vanhoorne,Valérie, Y1 - 2020/01/11/ PY - 2019/10/02/received PY - 2019/12/23/revised PY - 2019/12/26/accepted PY - 2020/1/15/pubmed PY - 2020/11/18/medline PY - 2020/1/15/entrez KW - Continuous manufacturing KW - Design of experiments KW - Formulation KW - Granule quality KW - Process variable KW - Twin screw granulation KW - Wet granulation SP - 119004 EP - 119004 JF - International journal of pharmaceutics JO - Int J Pharm VL - 576 N2 - Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically assessed the impact of different screw configurations and process settings on eight model formulations, varying in filler type, active pharmaceutical ingredient (API) characteristics and drug load. Although liquid to solid (L/S) ratio was the most influential variable for all formulations, also a large effect of the kneading element thickness was observed. Narrow kneading elements with a length to diameter ratio (L/D) of 1/6 had a significant detrimental effect on granule size, flow and strength compared to 1/4 L/D elements. The effects of kneading element distribution and barrel fill level were less pronounced. At low drug load, both filler types could be used to obtain granules with acceptable critical quality attributes (CQAs) for both APIs. Granulation at high drug load of the poorly soluble, poorly wettable API mebendazole proved challenging as it could not be processed using lactose as filler, in contrast to lactose/MCC. As formulations containing lactose/MCC as filler were less influenced by different screw configurations, process settings and API characteristics than formulations without MCC, lactose/MCC/HPMC was considered a promising platform formulation. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/31935475/Continuous_twin_screw_granulation:_A_complex_interplay_between_formulation_properties_process_settings_and_screw_design_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(19)31065-8 DB - PRIME DP - Unbound Medicine ER -