In-depth experimental analysis of pharmaceutical twin-screw wet granulation in view of detailed process understanding
| Autor: | Chris Vervaet, Daan Van Hauwermeiren, Thomas De Beer, Mary T. am Ende, Neil Turnbull, Davinia Brouckaert, Kai Lee, Maxim Verstraeten, Pankaj Doshi, David Wilsdon, Séverine Thérèse F.C. Mortier, Ingmar Nopens |
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| Rok vydání: | 2017 |
| Předmět: |
Chromatography
Materials science Chemistry Pharmaceutical Granule (cell biology) Plastics extrusion Pharmaceutical Science 02 engineering and technology Mechanics 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Screw speed 03 medical and health sciences Granulation 0302 clinical medicine Breakage Pharmaceutical Preparations Technology Pharmaceutical Particle size Wetting Particle Size 0210 nano-technology Porosity |
| Zdroj: | International journal of pharmaceutics. 529(1-2) |
| ISSN: | 1873-3476 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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