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In-depth experimental analysis of pharmaceutical twin-screw wet granulation in view of detailed process understanding.
Int J Pharm. 2017 Aug 30; 529(1-2):678-693.IJ

Abstract

Twin-screw wet granulation is gaining increasing interest within the pharmaceutical industry for the continuous manufacturing of solid oral dosage forms. However, limited prior fundamental physical understanding has been generated relating to the granule formation mechanisms and kinetics along the internal compartmental length of a twin-screw granulator barrel, and about how process settings, barrel screw configuration and formulation properties such as particle size, density and surface properties influence these mechanisms. One of the main reasons for this limited understanding is that experimental data is generally only collected at the exit of the twin-screw granulator barrel although the granule formation occurs spatially along the internal length of the barrel. The purpose of this study is to analyze the twin-screw wet granulation process using both hydrophilic and hydrophobic formulations, manufactured under different process settings such as liquid-to-solid ratio, mass throughput and screw speed, in such a way that the mechanisms occurring in the individual granulator barrel compartments (i.e., the wetting and different conveying and kneading compartments) and their impact upon granule formation are understood. To achieve this, a unique experimental setup was developed allowing granule characteristic data-collection such as size, shape, liquid and porosity distribution at the different compartments along the length of the granulator barrel. Moreover, granule characteristic information per granule size class was determined. The experimental results indicated that liquid-to-solid ratio is the most important factor dictating the formation of the granules and their corresponding properties, by regulating the degree of aggregation and breakage in the different compartments along the internal length of the twin-screw granulator barrel. Collecting appropriate and detailed experimental data about granule formation along the internal length of the granulator barrel is thus crucial for gaining fundamental physical understanding of the twin-screw wet granulation process.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium; BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Gent, Belgium.Worldwide Research and Development, Pfizer Inc., Sandwich, Kent, UK.Worldwide Research and Development, Pfizer Inc., Sandwich, Kent, UK.Worldwide Research and Development, Pfizer Inc., Sandwich, Kent, UK.Worldwide Research and Development, Pfizer Inc., Groton, CT, USA.Worldwide Research and Development, Pfizer Inc., Groton, CT, USA.Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium.BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Gent, Belgium.BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Gent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium. Electronic address: Thomas.DeBeer@UGent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28720539

Citation

Verstraeten, Maxim, et al. "In-depth Experimental Analysis of Pharmaceutical Twin-screw Wet Granulation in View of Detailed Process Understanding." International Journal of Pharmaceutics, vol. 529, no. 1-2, 2017, pp. 678-693.
Verstraeten M, Van Hauwermeiren D, Lee K, et al. In-depth experimental analysis of pharmaceutical twin-screw wet granulation in view of detailed process understanding. Int J Pharm. 2017;529(1-2):678-693.
Verstraeten, M., Van Hauwermeiren, D., Lee, K., Turnbull, N., Wilsdon, D., Am Ende, M., Doshi, P., Vervaet, C., Brouckaert, D., Mortier, S. T. F. C., Nopens, I., & Beer, T. (2017). In-depth experimental analysis of pharmaceutical twin-screw wet granulation in view of detailed process understanding. International Journal of Pharmaceutics, 529(1-2), 678-693. https://doi.org/10.1016/j.ijpharm.2017.07.045
Verstraeten M, et al. In-depth Experimental Analysis of Pharmaceutical Twin-screw Wet Granulation in View of Detailed Process Understanding. Int J Pharm. 2017 Aug 30;529(1-2):678-693. PubMed PMID: 28720539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In-depth experimental analysis of pharmaceutical twin-screw wet granulation in view of detailed process understanding. AU - Verstraeten,Maxim, AU - Van Hauwermeiren,Daan, AU - Lee,Kai, AU - Turnbull,Neil, AU - Wilsdon,David, AU - Am Ende,Mary, AU - Doshi,Pankaj, AU - Vervaet,Chris, AU - Brouckaert,Davinia, AU - Mortier,Séverine T F C, AU - Nopens,Ingmar, AU - Beer,Thomas De, Y1 - 2017/07/15/ PY - 2017/05/24/received PY - 2017/07/12/revised PY - 2017/07/14/accepted PY - 2017/7/20/pubmed PY - 2018/1/4/medline PY - 2017/7/20/entrez KW - Twin-screw wet granulation SP - 678 EP - 693 JF - International journal of pharmaceutics JO - Int J Pharm VL - 529 IS - 1-2 N2 - Twin-screw wet granulation is gaining increasing interest within the pharmaceutical industry for the continuous manufacturing of solid oral dosage forms. However, limited prior fundamental physical understanding has been generated relating to the granule formation mechanisms and kinetics along the internal compartmental length of a twin-screw granulator barrel, and about how process settings, barrel screw configuration and formulation properties such as particle size, density and surface properties influence these mechanisms. One of the main reasons for this limited understanding is that experimental data is generally only collected at the exit of the twin-screw granulator barrel although the granule formation occurs spatially along the internal length of the barrel. The purpose of this study is to analyze the twin-screw wet granulation process using both hydrophilic and hydrophobic formulations, manufactured under different process settings such as liquid-to-solid ratio, mass throughput and screw speed, in such a way that the mechanisms occurring in the individual granulator barrel compartments (i.e., the wetting and different conveying and kneading compartments) and their impact upon granule formation are understood. To achieve this, a unique experimental setup was developed allowing granule characteristic data-collection such as size, shape, liquid and porosity distribution at the different compartments along the length of the granulator barrel. Moreover, granule characteristic information per granule size class was determined. The experimental results indicated that liquid-to-solid ratio is the most important factor dictating the formation of the granules and their corresponding properties, by regulating the degree of aggregation and breakage in the different compartments along the internal length of the twin-screw granulator barrel. Collecting appropriate and detailed experimental data about granule formation along the internal length of the granulator barrel is thus crucial for gaining fundamental physical understanding of the twin-screw wet granulation process. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/28720539/In_depth_experimental_analysis_of_pharmaceutical_twin_screw_wet_granulation_in_view_of_detailed_process_understanding_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(17)30644-0 DB - PRIME DP - Unbound Medicine ER -