Continuous alternative to freeze drying: Manufacturing of cyclodextrin-based reconstitution powder from aqueous solution using scaled-up electrospinning

Panna Vass, Balázs Démuth, Attila Farkas, Edit Hirsch, Edina Szabó, Brigitta Nagy, Sune K. Andersen, Tamás Vigh, Geert Verreck, István Csontos, G. Marosi, Zsombor K. Nagy

Research output: Article

14 Citations (Scopus)

Abstract

The aims of this study were to evaluate electrospinning as a continuous alternative to freeze drying in the production of a reconstitution injection dosage form, and to prove that aqueous electrospinning can be realized with a high production rate at room temperature. High-speed electrospinning with a novel continuous cyclone collection was used to manufacture a formulation of the poorly water-soluble antifungal voriconazole (VOR) with sulfobutylether-β-cyclodextrin (SBE-β-CD). The freeze-dried, marketed product of this drug substance, Vfend® also contains SBE-β-CD as excipient. SBE-β-CD acted as a ‘quasi-polymer’ and it could be electrospun despite its low molecular mass (2163 Da). According to X-ray diffraction and differential scanning calorimetry, no traces of crystalline VOR were detectable in the fibers. Furthermore, Raman mapping and energy dispersive spectroscopy measurements showed a uniform distribution of amorphous VOR in the fibers. Reconstitution tests carried out with ground fibrous powder showed complete dissolution resulting in a clear solution after 30 s (similarly to Vfend®). The high productivity rate (~240 g/h) achieved using high-speed electrospinning makes this scaled-up, continuous and flexible manufacturing process capable of fulfilling the technological and capacity requirements of the pharmaceutical industry. This work shows that aqueous high-speed electrospinning, being a continuous and high-throughput process, is an economically viable production alternative to freeze drying.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalJournal of Controlled Release
Volume298
DOIs
Publication statusPublished - márc. 28 2019

Fingerprint

Freeze Drying
Cyclodextrins
Powders
Cyclonic Storms
Excipients
Differential Scanning Calorimetry
Dosage Forms
Drug Industry
X-Ray Diffraction
Spectrum Analysis
Polymers
Voriconazole
Injections
Temperature
Water
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Continuous alternative to freeze drying : Manufacturing of cyclodextrin-based reconstitution powder from aqueous solution using scaled-up electrospinning. / Vass, Panna; Démuth, Balázs; Farkas, Attila; Hirsch, Edit; Szabó, Edina; Nagy, Brigitta; Andersen, Sune K.; Vigh, Tamás; Verreck, Geert; Csontos, István; Marosi, G.; Nagy, Zsombor K.

In: Journal of Controlled Release, Vol. 298, 28.03.2019, p. 120-127.

Research output: Article

Vass, Panna ; Démuth, Balázs ; Farkas, Attila ; Hirsch, Edit ; Szabó, Edina ; Nagy, Brigitta ; Andersen, Sune K. ; Vigh, Tamás ; Verreck, Geert ; Csontos, István ; Marosi, G. ; Nagy, Zsombor K. / Continuous alternative to freeze drying : Manufacturing of cyclodextrin-based reconstitution powder from aqueous solution using scaled-up electrospinning. In: Journal of Controlled Release. 2019 ; Vol. 298. pp. 120-127.
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AU - Farkas, Attila

AU - Hirsch, Edit

AU - Szabó, Edina

AU - Nagy, Brigitta

AU - Andersen, Sune K.

AU - Vigh, Tamás

AU - Verreck, Geert

AU - Csontos, István

AU - Marosi, G.

AU - Nagy, Zsombor K.

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AB - The aims of this study were to evaluate electrospinning as a continuous alternative to freeze drying in the production of a reconstitution injection dosage form, and to prove that aqueous electrospinning can be realized with a high production rate at room temperature. High-speed electrospinning with a novel continuous cyclone collection was used to manufacture a formulation of the poorly water-soluble antifungal voriconazole (VOR) with sulfobutylether-β-cyclodextrin (SBE-β-CD). The freeze-dried, marketed product of this drug substance, Vfend® also contains SBE-β-CD as excipient. SBE-β-CD acted as a ‘quasi-polymer’ and it could be electrospun despite its low molecular mass (2163 Da). According to X-ray diffraction and differential scanning calorimetry, no traces of crystalline VOR were detectable in the fibers. Furthermore, Raman mapping and energy dispersive spectroscopy measurements showed a uniform distribution of amorphous VOR in the fibers. Reconstitution tests carried out with ground fibrous powder showed complete dissolution resulting in a clear solution after 30 s (similarly to Vfend®). The high productivity rate (~240 g/h) achieved using high-speed electrospinning makes this scaled-up, continuous and flexible manufacturing process capable of fulfilling the technological and capacity requirements of the pharmaceutical industry. This work shows that aqueous high-speed electrospinning, being a continuous and high-throughput process, is an economically viable production alternative to freeze drying.

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