caa a22 4500 445311908 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0461-2 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0461-2 Compositional Analysis of Low Quantities of Phase Separation in Hot-Melt-Extruded Solid Dispersions: A Combined Atomic Force Microscopy, Photothermal Fourier-Transform Infrared Microspectroscopy, and Localised Thermal Analysis Approach [Elektronische Daten] [Sheng Qi, Peter Belton, Kathrin Nollenberger, Andreas Gryczke, Duncan Craig] ABSTRACT: Purpose: To characterise phase separations in aged hot-melt-extruded solid dispersions at a micron to submicron scale. Methods: Hot-melt-extruded felodipine and Eudragit® E PO systems at a range of compositions were studied after a standard period of aging to allow phase separation to occur. The samples were characterised using combined nano-thermal analysis, photothermal FTIR microspectroscopy coupled with pulsed force mode AFM as a novel characterisation approach. Result: Crystalline felodipine presents in all formulations with drug loadings from 10-70% (w/w). In formulations with high drug loadings (50 and 70%), amorphous felodipine co-exists with crystalline forms, and higher drug concentration is observed in the centre compared to the outer surface of the extrudates. Drug crystal dimensions in extrudates with low drug loadings (10-30%) are small, in the micron to submicron range. We propose that uneven drug distribution is principally caused by processing-associated factors such as expansion of extrudates during extrusion. Conclusions: We have demonstrated that the novel combined approach allows site-specific characterisation of the extruded systems and that drug distribution may be uneven across the extrudates, with concomitant implications for understanding stability and drug release behaviour. Springer Science+Business Media, LLC, 2011 hot-melt-extruded solid dispersion nationallicence phase separation nationallicence photothermal FTIR microspectroscopy nationallicence pulsed force mode atomic force microscopy nationallicence supersaturation nationallicence Qi Sheng School of Pharmacy, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut Belton Peter School of Chemistry, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut Nollenberger Kathrin Evonik Röhm GmbH, Kirschenallee, 64293, Darmstadt, Germany aut Gryczke Andreas Evonik Röhm GmbH, Kirschenallee, 64293, Darmstadt, Germany aut Craig Duncan School of Pharmacy, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2311-2326 0724-8741 28:9<2311 2011 28 11095 https://doi.org/10.1007/s11095-011-0461-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0461-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Qi Sheng School of Pharmacy, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut NATIONALLICENCE 700 1- Belton Peter School of Chemistry, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut NATIONALLICENCE 700 1- Nollenberger Kathrin Evonik Röhm GmbH, Kirschenallee, 64293, Darmstadt, Germany aut NATIONALLICENCE 700 1- Gryczke Andreas Evonik Röhm GmbH, Kirschenallee, 64293, Darmstadt, Germany aut NATIONALLICENCE 700 1- Craig Duncan School of Pharmacy, University of East Anglia, NR4 7TJ, Norwich, Norfolk, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2311-2326 0724-8741 28:9<2311 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer