Downstream processing from hot-melt extrusion towards tablets : a quality by design approach
| Autor: | Pieter Rombouts, Valérie Vanhoorne, N. Bostijn, Chris Vervaet, T. De Beer, J.P. Remon, Lutz Nuhn, G. Verstraete, W. Grymonpré, S.Van Herck |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Hot Temperature
Technology and Engineering Tablet quality Solid dispersion Chemistry Pharmaceutical Drug Compounding Pharmaceutical Science 02 engineering and technology Die swell 030226 pharmacology & pharmacy Quality by Design 03 medical and health sciences Tableting 0302 clinical medicine MECHANICAL ENERGY Freezing Composite material COMPACTION PROPERTIES AMORPHOUS SOLID DISPERSIONS FORMULATION POWDER Quality by design Active ingredient SPECTROSCOPY DEGRADATION 021001 nanoscience & nanotechnology Amorphous solid Chemistry Raman spectroscopy Principle component analysis (PCA) PRESS SIMULATOR Pharmaceutical manufacturing Extrusion Hot-melt extrusion (HME) Powders 0210 nano-technology Critical quality attributes Tablets SOLUBLE DRUGS |
| Zdroj: | INTERNATIONAL JOURNAL OF PHARMACEUTICS |
| ISSN: | 0378-5173 |
| Popis: | Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200 degrees C, screw speed: 50-200 rpm, throughput: 0.2-0.5 kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus (R)-Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (ie. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating > 3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load). |
| Databáze: | OpenAIRE |
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