caa a22 4500 445313110 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0456-z doi (NATIONALLICENCE)springer-10.1007/s11095-011-0456-z Intact Nanoparticulate Indomethacin in Fast-Dissolving Carrier Particles by Combined Wet Milling and Aerosol Flow Reactor Methods [Elektronische Daten] [Timo Laaksonen, Peng Liu, Antti Rahikkala, Leena Peltonen, Esko Kauppinen, Jouni Hirvonen, Kristiina Järvinen, Janne Raula] ABSTRACT: Purpose: Drug development is often hindered by a drug's low dissolution rate. We present a method to increase dissolution rate of a drug powder by producing crystalline nanoparticles that are dispersed in carrier microparticles. Methods: Indomethacin crystals of a few hundred nanometers are prepared by media milling using poloxamer 188 as a stabilizer. Nanoparticles are embedded into microparticles with a mannitol matrix and an L-leucine coating layer using an aerosol flow reactor method. Results: Microparticles stabilize the primary nanoparticles in an intact crystalline form and release them when re-dispersed in aqueous medium. Secondary microparticle structure dissolves rapidly, resulting in a fast release and dissolution of indomethacin. In this manner, it is possible to change the surface layer of the particles from the one needed for nanoparticle production to one more suitable for process formulation of pharmaceuticals for, e.g., tablet or pulmonary products. Conclusions: Particle assemblies where nano-sized crystalline drug domains are embedded in solid microparticles are presented. The present work is a promising approach towards a "nanos-in-micros” concept as a tool for pharmaceutical nanoparticle processing. Springer Science+Business Media, LLC, 2011 aerosol flow reactor nationallicence drug dissolution nationallicence media milling nationallicence microparticles nationallicence nanoparticles nationallicence Laaksonen Timo Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut Liu Peng Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut Rahikkala Antti Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut Peltonen Leena Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut Kauppinen Esko Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut Hirvonen Jouni Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut Järvinen Kristiina School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland aut Raula Janne Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2403-2411 0724-8741 28:10<2403 2011 28 11095 https://doi.org/10.1007/s11095-011-0456-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0456-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Laaksonen Timo Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Liu Peng Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Rahikkala Antti Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut NATIONALLICENCE 700 1- Peltonen Leena Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Kauppinen Esko Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut NATIONALLICENCE 700 1- Hirvonen Jouni Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box56, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Järvinen Kristiina School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Raula Janne Department of Applied Physics, Aalto University School of Science, P.O. Box15100, 00076, Aalto, Finland aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2403-2411 0724-8741 28:10<2403 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer