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Identification of continuous twin-screw melt granulation mechanisms for different screw configurations, process settings and formulation.
Int J Pharm. 2023 Jan 05; 630:122322.IJ

Abstract

Twin-screw melt granulation (TSMG) is a promising continuous manufacturing technology for the processing of high drug load formulations and to formulate heat- and moisture-sensitive active pharmaceutical ingredients (APIs). This study evaluates the influence of process parameters for TSMG, mainly focusing on the effect of the screw configuration combined with screw speed, throughput and barrel temperature, to elucidate the melt granulation mechanisms. For the kneading zone, the stagger angle was varied between 30°, 60° and 90°, and investigated for both the forward and the reversed direction. In addition to the process parameters, the influence of the formulation differing in their API-binder miscibility was evaluated. As responses, the granule (size, friability and porosity) and process properties such as torque were evaluated, indicating that the screw configuration is the most influential factor. Nucleation, consolidation and breakage are the granulation mechanisms for the forward and the neutral configuration, while consolidation and densification with shear elongation are identified for the reversed configuration. The formulations differ mainly in the forward and neutral configuration since the immiscible formulation shows a bimodal granule size distribution with a larger fraction of fines and weaker granules is obtained. For the reversed configuration, similar granulation mechanisms are seen for both formulations.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Van de Steene S
Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences Ghent University, Ghent, Belgium. Electronic address: shana.vandesteene@ugent.be.
Van Renterghem J
Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences Ghent University, Ghent, Belgium.
Vanhoorne V
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences Ghent University, Ghent, Belgium.
Vervaet C
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences Ghent University, Ghent, Belgium.
Kumar A
Pharmaceutical Engineering Research Group, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
De Beer T
Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences Ghent University, Ghent, Belgium.

MeSH

Particle SizeExcipientsPorosityTemperatureTechnology, PharmaceuticalDrug CompoundingTablets

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36448825

Citation

Van de Steene, S, et al. "Identification of Continuous Twin-screw Melt Granulation Mechanisms for Different Screw Configurations, Process Settings and Formulation." International Journal of Pharmaceutics, vol. 630, 2023, p. 122322.
Van de Steene S, Van Renterghem J, Vanhoorne V, et al. Identification of continuous twin-screw melt granulation mechanisms for different screw configurations, process settings and formulation. Int J Pharm. 2023;630:122322.
Van de Steene, S., Van Renterghem, J., Vanhoorne, V., Vervaet, C., Kumar, A., & De Beer, T. (2023). Identification of continuous twin-screw melt granulation mechanisms for different screw configurations, process settings and formulation. International Journal of Pharmaceutics, 630, 122322. https://doi.org/10.1016/j.ijpharm.2022.122322
Van de Steene S, et al. Identification of Continuous Twin-screw Melt Granulation Mechanisms for Different Screw Configurations, Process Settings and Formulation. Int J Pharm. 2023 Jan 5;630:122322. PubMed PMID: 36448825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of continuous twin-screw melt granulation mechanisms for different screw configurations, process settings and formulation. AU - Van de Steene,S, AU - Van Renterghem,J, AU - Vanhoorne,V, AU - Vervaet,C, AU - Kumar,A, AU - De Beer,T, Y1 - 2022/10/30/ PY - 2022/8/13/received PY - 2022/10/4/revised PY - 2022/10/15/accepted PY - 2022/12/1/pubmed PY - 2022/12/21/medline PY - 2022/11/30/entrez KW - Continuous manufacturing KW - Granulation mechanism KW - Twin-screw melt granulation SP - 122322 EP - 122322 JF - International journal of pharmaceutics JO - Int J Pharm VL - 630 N2 - Twin-screw melt granulation (TSMG) is a promising continuous manufacturing technology for the processing of high drug load formulations and to formulate heat- and moisture-sensitive active pharmaceutical ingredients (APIs). This study evaluates the influence of process parameters for TSMG, mainly focusing on the effect of the screw configuration combined with screw speed, throughput and barrel temperature, to elucidate the melt granulation mechanisms. For the kneading zone, the stagger angle was varied between 30°, 60° and 90°, and investigated for both the forward and the reversed direction. In addition to the process parameters, the influence of the formulation differing in their API-binder miscibility was evaluated. As responses, the granule (size, friability and porosity) and process properties such as torque were evaluated, indicating that the screw configuration is the most influential factor. Nucleation, consolidation and breakage are the granulation mechanisms for the forward and the neutral configuration, while consolidation and densification with shear elongation are identified for the reversed configuration. The formulations differ mainly in the forward and neutral configuration since the immiscible formulation shows a bimodal granule size distribution with a larger fraction of fines and weaker granules is obtained. For the reversed configuration, similar granulation mechanisms are seen for both formulations. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/36448825/Identification_of_continuous_twin_screw_melt_granulation_mechanisms_for_different_screw_configurations_process_settings_and_formulation_ DB - PRIME DP - Unbound Medicine ER -