caa a22 4500 445312874 CHVBK 20190327083712.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0306-4 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0306-4 Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions [Elektronische Daten] [Matthias Lauer, Olaf Grassmann, Monira Siam, Joseph Tardio, Laurence Jacob, Susanne Page, Johannes Kindt, Andreas Engel, Jochem Alsenz] ABSTRACT: Purpose: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. Methods: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. Results: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. Conclusions: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few days. The Author(s), 2010 amorphous formulation nationallicence raman microscopy nationallicence solid dispersion nationallicence stability prediction nationallicence AFM nationallicence AFM : atomic force microscopy nationallicence API : active pharmaceutical ingredient nationallicence CETP2 : CETP inhibitor (2) nationallicence Eudragit L100 : polymethacrylate nationallicence HME : hot-melt extrusion nationallicence HPMCAS MF : hydroxypropyl methylcellulose acetate succinate nationallicence NK1(1) : NK1 antagonist (1) nationallicence PVP K30 : polyvinylpyrrolidone K30 nationallicence PVP17PF : polyvinylpyrrolidone 17PF nationallicence PVP VA 64 : copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate nationallicence RH : relative humidity nationallicence SEM : scanning electron microscopy nationallicence T : temperature nationallicence TEM : transmission electron microscopy nationallicence Lauer Matthias Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland aut Grassmann Olaf F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland aut Siam Monira F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland aut Tardio Joseph F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut Jacob Laurence F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut Page Susanne F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut Kindt Johannes Bruker Nano GmbH, Dynamostrasse 19, 68165, Mannheim, Germany aut Engel Andreas Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland aut Alsenz Jochem F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 572-584 0724-8741 28:3<572 2011 28 11095 https://doi.org/10.1007/s11095-010-0306-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0306-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lauer Matthias Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland aut NATIONALLICENCE 700 1- Grassmann Olaf F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Siam Monira F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Tardio Joseph F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Jacob Laurence F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Page Susanne F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Kindt Johannes Bruker Nano GmbH, Dynamostrasse 19, 68165, Mannheim, Germany aut NATIONALLICENCE 700 1- Engel Andreas Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland aut NATIONALLICENCE 700 1- Alsenz Jochem F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 572-584 0724-8741 28:3<572 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer