title: High speed electrospinning for scaled-up production of amorphous solid dispersion of itraconazole.
abstract: High speed electrospinning (HSES), compatible with pharmaceutical industry, was used to demonstrate the viability of the preparation of drug-loaded polymer nanofibers with radically higher productivity than the known single-needle electrospinning (SNES) setup. Poorly water-soluble itraconazole (ITRA) was formulated with PVPVA64 matrix polymer using four different solvent-based methods such as HSES, SNES, spray drying (SD) and film casting (FC). The formulations were assessed in terms of improvement in the dissolution rate of ITRA (using a "tapped basket" dissolution configuration) and analysed by SEM, DSC and XRPD. Despite the significantly increased productivity of HSES, the obtained morphology was very similar to the SNES nanofibrous material. ITRA transformed into an amorphous form, according to the DSC and XRPD results, in most cases except the FC samples. The limited dissolution of crystalline ITRA could be highly improved: fast dissolution occurred (>90% within 10min) in the cases of both (the scaled-up and the single-needle) types of electrospun fibers, while the improvement in the dissolution rate of the spray-dried microspheres was significantly lower. Production of amorphous solid dispersions (ASDs) with the HSES system proved to be flexibly scalable and easy to integrate into a continuous pharmaceutical manufacturing line, which opens new routes for the development of industrially relevant nanopharmaceuticals.
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary. Electronic address: zsknagy@oct.bme.hu.
authors.forename: Zsombor K
authors.initials: ZK
authors.lastname: Nagy
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Démuth
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary.
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Pataki
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Vigh
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary; Budapest University of Technology and Economics, Department of Polymer Engineering, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Szabó
authors.affiliation: Budapest University of Technology and Economics, Department of Polymer Engineering, Hungary.
authors.forename: Kolos
authors.initials: K
authors.lastname: Molnár
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary; Budapest University of Technology and Economics, Department of Machine and Industrial Product Design, Hungary.
authors.forename: Bence T
authors.initials: BT
authors.lastname: Schmidt
authors.affiliation: Budapest University of Technology and Economics, Department of Machine and Industrial Product Design, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Horák
authors.affiliation: Budapest University of Technology and Economics, Department of Organic Chemistry and Technology, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Marosi
authors.affiliation: Janssen Research and Development, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Verreck
authors.affiliation: Janssen Research and Development, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Van Assche
authors.affiliation: Janssen Research and Development, Belgium.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Brewster
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004345:Drug Industry / Q000379:methods; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry; D008863:Microspheres; D057139:Nanofibers; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D011108:Polymers; D012997:Solvents; D017964:Itraconazole
keywords: Amorphous solid dispersion; Continuous nanoformulation; Dissolution enhancement; Electrospinning; Itraconazole; Scaling-up