caa a22 4500 44531298X CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0324-2 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0324-2 Comparison Between Hot-Melt Extrusion and Spray-Drying for Manufacturing Solid Dispersions of the Graft Copolymer of Ethylene Glycol and Vinylalcohol [Elektronische Daten] [Sandra Guns, Aswin Dereymaker, Pieterjan Kayaert, Vincent Mathot, Johan Martens, Guy Van den Mooter] ABSTRACT: Purpose: To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated. Method: The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction. Results: Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque. Conclusion: The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit. Springer Science+Business Media, LLC, 2010 hot-melt extrusion nationallicence Kollicoat IR nationallicence poly(ethylene-g-vinylalcohol) nationallicence solid dispersions nationallicence spray-drying nationallicence Guns Sandra Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut Dereymaker Aswin Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut Kayaert Pieterjan Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut Mathot Vincent SciTe B.V., Ridder Vosstraat 6, 6162 AX, Geleen, the Netherlands aut Martens Johan Centre for Surface Chemistry and Catalysis, Catholic University of Leuven, Kasteelpark Arenberg 23, 3001, Heverlee, Belgium aut Van den Mooter Guy Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 673-682 0724-8741 28:3<673 2011 28 11095 https://doi.org/10.1007/s11095-010-0324-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0324-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Guns Sandra Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut NATIONALLICENCE 700 1- Dereymaker Aswin Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut NATIONALLICENCE 700 1- Kayaert Pieterjan Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut NATIONALLICENCE 700 1- Mathot Vincent SciTe B.V., Ridder Vosstraat 6, 6162 AX, Geleen, the Netherlands aut NATIONALLICENCE 700 1- Martens Johan Centre for Surface Chemistry and Catalysis, Catholic University of Leuven, Kasteelpark Arenberg 23, 3001, Heverlee, Belgium aut NATIONALLICENCE 700 1- Van den Mooter Guy Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box921, 3000, Leuven, Belgium aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 673-682 0724-8741 28:3<673 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer