title: Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning.
abstract: In this research the long-term stability (one year) of amorphous solid dispersions (ASDs) prepared by high speed electrospinning was investigated at 25 °C/60% relative humidity (RH) (closed conditions) and 40 °C/75% RH (open conditions). Single needle electrospinning and film casting were applied as reference technologies. Itraconazole (ITR) was used as the model API in 40% concentration and the ASDs consisted of either one of the following polymers as a comparison: polyvinylpyrrolidone-vinyl acetate 6:4 copolymer (no hydrogen bonds between API and polymer) and hydroxypropyl methylcellulose (possible hydrogen bonds between oxo or tertiary nitrogen function of API and hydroxyl moiety of polymer). DSC, XRPD and dissolution characteristics of samples at 0, 3 and 12 months were investigated. In addition, Raman maps of certain electrospun ASDs were assessed to investigate crystallinity. A new chemometric method, based on Multivariate Curve Resolution-Alternating Least Squares algorithm, was developed to calculate the spectrum of amorphous ITR in the matrices and to determine the crystalline/amorphous ratio of aged samples. As it was expected ITR in single needle electrospun SDs was totally amorphous at the beginning, in addition hydroxypropyl methylcellulose could keep ITR in this form at 40 °C/75% RH up to one year due to the hydrogen bonds and high glass transition temperature of the SD. In polyvinylpyrrolidone-vinyl acetate matrix ITR remained amorphous at 25 °C/60% RH throughout one year. Materials prepared by scaled-up, high throughput version of electrospinning, which is compatible with pharmaceutical industry, also gained the same quality. Therefore these ASDs are industrially applicable and with an appropriate downstream process it would be possible to bring them to the market.
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Démuth
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Farkas
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Pataki
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Szabó
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Borbás
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: P L
authors.initials: PL
authors.lastname: Sóti
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Vigh
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: É
authors.initials: É
authors.lastname: Kiserdei
authors.affiliation: Department of Manufacturing Science and Engineering, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Farkas
authors.affiliation: Drug Product Development, Janssen R&D, 2340 Beerse, Turnhoutseweg 30, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Mensch
authors.affiliation: Drug Product Development, Janssen R&D, 2340 Beerse, Turnhoutseweg 30, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Verreck
authors.affiliation: Drug Product Development, Janssen R&D, 2340 Beerse, Turnhoutseweg 30, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Van Assche
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Marosi
authors.affiliation: Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3., Hungary. Electronic address: zsknagy@oct.bme.hu.
authors.forename: Z K
authors.initials: ZK
authors.lastname: Nagy
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004355:Drug Stability; D065347:Hypromellose Derivatives / Q000032:analysis / Q000138:chemical synthesis; D009339:Needles; D011108:Polymers / Q000032:analysis* / Q000138:chemical synthesis*; D011205:Povidone / Q000032:analysis / Q000138:chemical synthesis; D014961:X-Ray Diffraction
chemical_list: D011108:Polymers; D065347:Hypromellose Derivatives; D011205:Povidone
keywords: Amorphous solid dispersion; High speed electrospinning; Long-term stability; Oral drug delivery; Raman mapping