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Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach.
Int J Pharm X. 2021 Dec; 3:100077.IJ

Abstract

Despite significant advances in the research domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent mitigation of the impact of this variability on the manufacturing process and drug product was recently stressed in the Draft Guidance for Industry on Quality Considerations for Continuous Manufacturing by the U.S. Food and Drug Administration (FDA). Therefore, this study assessed the impact of microcrystalline cellulose (MCC) batch-to-batch variability and process settings in a continuous twin screw wet granulation and semi-continuous drying line. Based on extensive raw material characterization and subsequent principal component analysis, raw material variability was quantitatively introduced in the design of experiments approach by means of t1 and t2 scores. L/S ratio had a larger effect on critical granule attributes and processability than screw speed and drying time. A large impact of the t1 and t2 scores was found, indicating the importance of raw material attributes. For the studied formulation, it was concluded that MCC batches with a low water binding capacity, low moisture content and high bulk density generated granules with the most desirable quality attributes. Additionally, an innovative and quantitative approach towards mitigating batch-to-batch variability of raw materials was proposed, which is also applicable for additional excipients and APIs.

Authors+Show Affiliations

Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.Drug Product Development, Janssen Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.Drug Product Development, Janssen Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.Drug Product Development, Janssen Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.Drug Product Development, Janssen Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33870182

Citation

Portier, Christoph, et al. "Continuous Twin Screw Granulation: Impact of Microcrystalline Cellulose Batch-to-batch Variability During Granulation and Drying - a QbD Approach." International Journal of Pharmaceutics: X, vol. 3, 2021, p. 100077.
Portier C, Vigh T, Di Pretoro G, et al. Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach. Int J Pharm X. 2021;3:100077.
Portier, C., Vigh, T., Di Pretoro, G., Leys, J., Klingeleers, D., De Beer, T., Vervaet, C., & Vanhoorne, V. (2021). Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach. International Journal of Pharmaceutics: X, 3, 100077. https://doi.org/10.1016/j.ijpx.2021.100077
Portier C, et al. Continuous Twin Screw Granulation: Impact of Microcrystalline Cellulose Batch-to-batch Variability During Granulation and Drying - a QbD Approach. Int J Pharm X. 2021;3:100077. PubMed PMID: 33870182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach. AU - Portier,Christoph, AU - Vigh,Tamas, AU - Di Pretoro,Giustino, AU - Leys,Jan, AU - Klingeleers,Didier, AU - De Beer,Thomas, AU - Vervaet,Chris, AU - Vanhoorne,Valérie, Y1 - 2021/03/19/ PY - 2021/03/17/received PY - 2021/03/18/accepted PY - 2021/4/19/entrez PY - 2021/4/20/pubmed PY - 2021/4/20/medline KW - API, Active Pharmaceutical Ingredient KW - BET, Brunauer Emmett and Teller KW - Batch-to-batch variability KW - Com, Commercial batch KW - Continuous manufacturing KW - Design of experiments KW - DoE, Design of Experiments KW - Dx (d10, d50, d90), Size in microns at which x volume% of the particles is smaller than dx KW - Formulation development KW - HR, Hausner Ratio KW - L/D, Length-to-diameter KW - L/S, Liquid to solid KW - LOD, Loss on drying KW - MCC, Microcrystalline Cellulose KW - PCA, Principle Component Analysis KW - PSD, Particle size distribution KW - QbD, Quality-by-Design KW - Quality-by-Design KW - RTD, Residence Time Distribution KW - SCE, Size Control Element KW - SSA, Specific Surface Area KW - Twin screw granulation KW - WBC, Water Binding Capacity KW - Wet granulation KW - rpm, Revolutions Per Minute SP - 100077 EP - 100077 JF - International journal of pharmaceutics: X JO - Int J Pharm X VL - 3 N2 - Despite significant advances in the research domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent mitigation of the impact of this variability on the manufacturing process and drug product was recently stressed in the Draft Guidance for Industry on Quality Considerations for Continuous Manufacturing by the U.S. Food and Drug Administration (FDA). Therefore, this study assessed the impact of microcrystalline cellulose (MCC) batch-to-batch variability and process settings in a continuous twin screw wet granulation and semi-continuous drying line. Based on extensive raw material characterization and subsequent principal component analysis, raw material variability was quantitatively introduced in the design of experiments approach by means of t1 and t2 scores. L/S ratio had a larger effect on critical granule attributes and processability than screw speed and drying time. A large impact of the t1 and t2 scores was found, indicating the importance of raw material attributes. For the studied formulation, it was concluded that MCC batches with a low water binding capacity, low moisture content and high bulk density generated granules with the most desirable quality attributes. Additionally, an innovative and quantitative approach towards mitigating batch-to-batch variability of raw materials was proposed, which is also applicable for additional excipients and APIs. SN - 2590-1567 UR - https://www.unboundmedicine.com/medline/citation/33870182/Continuous_twin_screw_granulation:_Impact_of_microcrystalline_cellulose_batch_to_batch_variability_during_granulation_and_drying___A_QbD_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2590-1567(21)00006-2 DB - PRIME DP - Unbound Medicine ER -
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