title: NANEX: Process design and optimization.
abstract: Previously, we introduced a one-step nano-extrusion (NANEX) process for transferring aqueous nano-suspensions into solid formulations directly in the liquid phase. Nano-suspensions were fed into molten polymers via a side-feeding device and excess water was eliminated via devolatilization. However, the drug content in nano-suspensions is restricted to 30 % (w/w), and obtaining sufficiently high drug loadings in the final formulation requires the processing of high water amounts and thus a fundamental process understanding. To this end, we investigated four polymers with different physicochemical characteristics (Kollidon(®) VA64, Eudragit(®) E PO, HPMCAS and PEG 20000) in terms of their maximum water uptake/removal capacity. Process parameters as throughput and screw speed were adapted and their effect on the mean residence time and filling degree was studied. Additionally, one-dimensional discretization modeling was performed to examine the complex interactions between the screw geometry and the process parameters during water addition/removal. It was established that polymers with a certain water miscibility/solubility can be manufactured via NANEX. Long residence times of the molten polymer in the extruder and low filling degrees in the degassing zone favored the addition/removal of significant amounts of water. The residual moisture content in the final extrudates was comparable to that of extrudates manufactured without water.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Ramona
authors.initials: R
authors.lastname: Baumgartner
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Josip
authors.initials: J
authors.lastname: Matić
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Universitätsplatz 1, 8010 Graz, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Schrank
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Laske
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Khinast
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Universitätsplatz 1, 8010 Graz, Austria. Electronic address: eva.roblegg@uni-graz.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008768:Methylmethacrylates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D013535:Suspensions / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D008768:Methylmethacrylates; D011108:Polymers; D011759:Pyrrolidines; D013535:Suspensions; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014867:Water; C102808:Eudragit-E; D011092:Polyethylene Glycols; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose
keywords: Devolatilization; Mean residence time; NANEX design and optimization; One-step nano-extrusion process; Screw configuration; Water integration capacity