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Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding.
Eur J Pharm Biopharm. 2019 Feb; 135:49-60.EJ

Abstract

Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e., blend) existing of a highly dosed very poorly flowing active pharmaceutical ingredient (API) leading to insufficient feeding capacity was investigated. Furthermore, the API showed very high batch-to-batch variability in raw material properties dominating the formulation blend properties. Formulation changes were evaluated to improve the flowability of the blends and to mitigate the impact of API batch-to-batch variability on the twin-screw feeding. Herewith, feeding evaluation tests and an extensive material characterization of the reformulated blends were performed to assess the impact of the formulation changes upon continuous twin-screw feeding. The transfer of the glidant from extra-granular to intra-granular phase allowed to improve the flowability of the blends. A sufficient feeding capacity for the downstream process and a mitigation of the impact of batch-to-batch variability of the API upon twin-screw feeding of the blends could be achieved. No effect of the formulation or of the API properties on the feeding stability was observed. The material characterization of the blends allowed identifying the material attributes which were critical for continuous twin-screw feeding (i.e., bulk density, mass charge and powder cohesiveness).

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Drug Delivery Design and Development, UCB, Braine l'Alleud, Belgium.Drug Delivery Design and Development, UCB, Braine l'Alleud, Belgium.Drug Delivery Design and Development, UCB, Braine l'Alleud, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30582959

Citation

Stauffer, F, et al. "Managing Active Pharmaceutical Ingredient Raw Material Variability During Twin-screw Blend Feeding." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 135, 2019, pp. 49-60.
Stauffer F, Vanhoorne V, Pilcer G, et al. Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding. Eur J Pharm Biopharm. 2019;135:49-60.
Stauffer, F., Vanhoorne, V., Pilcer, G., Chavez, P. F., Schubert, M. A., Vervaet, C., & De Beer, T. (2019). Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 135, 49-60. https://doi.org/10.1016/j.ejpb.2018.12.012
Stauffer F, et al. Managing Active Pharmaceutical Ingredient Raw Material Variability During Twin-screw Blend Feeding. Eur J Pharm Biopharm. 2019;135:49-60. PubMed PMID: 30582959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding. AU - Stauffer,F, AU - Vanhoorne,V, AU - Pilcer,G, AU - Chavez,Pierre-François, AU - Schubert,M A, AU - Vervaet,C, AU - De Beer,T, Y1 - 2018/12/22/ PY - 2018/03/30/received PY - 2018/10/31/revised PY - 2018/12/20/accepted PY - 2018/12/26/pubmed PY - 2019/4/6/medline PY - 2018/12/25/entrez KW - Continuous manufacturing KW - Managing active pharmaceutical ingredient variability KW - Material properties KW - Multivariate data analysis KW - Quality by design KW - Twin-screw feeding SP - 49 EP - 60 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 135 N2 - Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e., blend) existing of a highly dosed very poorly flowing active pharmaceutical ingredient (API) leading to insufficient feeding capacity was investigated. Furthermore, the API showed very high batch-to-batch variability in raw material properties dominating the formulation blend properties. Formulation changes were evaluated to improve the flowability of the blends and to mitigate the impact of API batch-to-batch variability on the twin-screw feeding. Herewith, feeding evaluation tests and an extensive material characterization of the reformulated blends were performed to assess the impact of the formulation changes upon continuous twin-screw feeding. The transfer of the glidant from extra-granular to intra-granular phase allowed to improve the flowability of the blends. A sufficient feeding capacity for the downstream process and a mitigation of the impact of batch-to-batch variability of the API upon twin-screw feeding of the blends could be achieved. No effect of the formulation or of the API properties on the feeding stability was observed. The material characterization of the blends allowed identifying the material attributes which were critical for continuous twin-screw feeding (i.e., bulk density, mass charge and powder cohesiveness). SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/30582959/Managing_active_pharmaceutical_ingredient_raw_material_variability_during_twin_screw_blend_feeding_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(18)30425-9 DB - PRIME DP - Unbound Medicine ER -