From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor
| Autor: | Jörg Jurascheck, Christine Petzoldt, Thomas Olpp, Lydia Helmdach, Bruno Baumgartner, Martin P. Feth, Joachim Ulrich, Christoph Tappertzhofen, Norbert Nagel, Winfried Heyse |
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| Rok vydání: | 2012 |
| Předmět: |
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Molecular Materials science Chemistry Pharmaceutical Cathepsin K Pharmaceutical Science Pilot Projects Crystallography X-Ray Spectrum Analysis Raman Wet-milling law.invention symbols.namesake law Process optimization Crystallization Enzyme Inhibitors Particle Size Calorimetry Differential Scanning General Medicine Cathepsins Crystallography Pilot plant Polymorphism (materials science) Chemical engineering Spray drying Thermogravimetry symbols Microscopy Electron Scanning Thermodynamics Raman spectroscopy Single crystal Powder Diffraction Biotechnology |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 83(3) |
| ISSN: | 1873-3441 |
| Popis: | The solid-state development for the low dose drug molecule SAR114137, a selective and reversible inhibitor of cysteine cathepsin S/K, is reported. Six polymorphic forms as well as various solvate phases were discovered by an extensive polymorphism screening. The solid phase characterizations revealed that phase 1, from which a single crystal structure could be obtained, is the thermodynamically most stable form and therefore it was chosen for pharmaceutical development. The successful scale-up from development laboratory into pilot plant for the crystallization and drying processes is presented. Testing of different drying techniques, like agitated drying in conical or filter dryers as well as spray drying, proved them to be very promising alternatives to the conventional tray drying process and might be used during the industrialization phase of the project. The use of online analytical tools (e.g., Raman spectroscopy) for a better process understanding and as tools for process optimization is shown. Furthermore, wet milling by ultrasound was performed on laboratory scale and discussed as potential option to reach the desired particle size distribution necessary for a good content uniformity of the API in an oral formulation. |
| Databáze: | OpenAIRE |
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