Controlled-release solid dispersions of Eudragit® FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion

Attila Balogh, Balázs Farkas, András Domokos, Attila Farkas, Balázs Démuth, Enikő Borbás, Brigitta Nagy, G. Marosi, Zsombor Kristóf Nagy

Research output: Article

18 Citations (Scopus)

Abstract

Eudragit® FS (EudFS), a novel anionic metachrylate terpolymer with pH dependent solubility was processed using electrospinning (ES) for the first time and melt extrusion (EX) for controlled delivery of a poorly water-soluble model drug, spironolactone (SPIR). Optimization of ES showed good spinnability of EudFS. Nanofibrous products could be obtained using fairly polar solvents (acetone, dichloromethane-ethanol (1:1), dimethylformamide). Drug-loaded nanofibers were prepared using novel alternating current electrospinning at multiple times higher throughput than direct current electrospinning. Melt extrusion proved to be also a feasible technique to prepare EudFS-based solid dispersions above 100 °C. The viscoelasticity of EudFS melts was characterized in terms of temperature, frequency and heating time dependence. Solid state analyses revealed amorphous SPIR content in the electrospun fibers, however, signs of residual crystallinity could be detected in the extruded sample with 20% SPIR according to XRPD and EDS mapping. In vitro dissolution of the EudFS-based solid dispersions showed superior control of drug release compared to the physical mixture of crystalline SPIR and EudFS. At gastric pH where the polymer is insoluble the drug was more restrained in the ground extrudates than in the electrospun fibers. This state was followed by a quick burst as the pH rose to 7.4. EudFS, well-processed by electrospinning or melt extrusion, proved to be a promising matrix for oral drug delivery applications especially targeting the colon.

Original languageEnglish
Pages (from-to)406-417
Number of pages12
JournalEuropean Polymer Journal
Volume95
DOIs
Publication statusPublished - okt. 1 2017

Fingerprint

Spironolactone
Electrospinning
Dispersions
Extrusion
drugs
delivery
Pharmaceutical Preparations
Terpolymers
fibers
Fibers
viscoelasticity
Dichloromethane
Viscoelasticity
Dimethylformamide
Nanofibers
Drug delivery
Acetone
acetone
time dependence
Energy dispersive spectroscopy

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Polymers and Plastics
  • Organic Chemistry

Cite this

Controlled-release solid dispersions of Eudragit® FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion. / Balogh, Attila; Farkas, Balázs; Domokos, András; Farkas, Attila; Démuth, Balázs; Borbás, Enikő; Nagy, Brigitta; Marosi, G.; Nagy, Zsombor Kristóf.

In: European Polymer Journal, Vol. 95, 01.10.2017, p. 406-417.

Research output: Article

Balogh, Attila ; Farkas, Balázs ; Domokos, András ; Farkas, Attila ; Démuth, Balázs ; Borbás, Enikő ; Nagy, Brigitta ; Marosi, G. ; Nagy, Zsombor Kristóf. / Controlled-release solid dispersions of Eudragit® FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion. In: European Polymer Journal. 2017 ; Vol. 95. pp. 406-417.
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AU - Balogh, Attila

AU - Farkas, Balázs

AU - Domokos, András

AU - Farkas, Attila

AU - Démuth, Balázs

AU - Borbás, Enikő

AU - Nagy, Brigitta

AU - Marosi, G.

AU - Nagy, Zsombor Kristóf

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N2 - Eudragit® FS (EudFS), a novel anionic metachrylate terpolymer with pH dependent solubility was processed using electrospinning (ES) for the first time and melt extrusion (EX) for controlled delivery of a poorly water-soluble model drug, spironolactone (SPIR). Optimization of ES showed good spinnability of EudFS. Nanofibrous products could be obtained using fairly polar solvents (acetone, dichloromethane-ethanol (1:1), dimethylformamide). Drug-loaded nanofibers were prepared using novel alternating current electrospinning at multiple times higher throughput than direct current electrospinning. Melt extrusion proved to be also a feasible technique to prepare EudFS-based solid dispersions above 100 °C. The viscoelasticity of EudFS melts was characterized in terms of temperature, frequency and heating time dependence. Solid state analyses revealed amorphous SPIR content in the electrospun fibers, however, signs of residual crystallinity could be detected in the extruded sample with 20% SPIR according to XRPD and EDS mapping. In vitro dissolution of the EudFS-based solid dispersions showed superior control of drug release compared to the physical mixture of crystalline SPIR and EudFS. At gastric pH where the polymer is insoluble the drug was more restrained in the ground extrudates than in the electrospun fibers. This state was followed by a quick burst as the pH rose to 7.4. EudFS, well-processed by electrospinning or melt extrusion, proved to be a promising matrix for oral drug delivery applications especially targeting the colon.

AB - Eudragit® FS (EudFS), a novel anionic metachrylate terpolymer with pH dependent solubility was processed using electrospinning (ES) for the first time and melt extrusion (EX) for controlled delivery of a poorly water-soluble model drug, spironolactone (SPIR). Optimization of ES showed good spinnability of EudFS. Nanofibrous products could be obtained using fairly polar solvents (acetone, dichloromethane-ethanol (1:1), dimethylformamide). Drug-loaded nanofibers were prepared using novel alternating current electrospinning at multiple times higher throughput than direct current electrospinning. Melt extrusion proved to be also a feasible technique to prepare EudFS-based solid dispersions above 100 °C. The viscoelasticity of EudFS melts was characterized in terms of temperature, frequency and heating time dependence. Solid state analyses revealed amorphous SPIR content in the electrospun fibers, however, signs of residual crystallinity could be detected in the extruded sample with 20% SPIR according to XRPD and EDS mapping. In vitro dissolution of the EudFS-based solid dispersions showed superior control of drug release compared to the physical mixture of crystalline SPIR and EudFS. At gastric pH where the polymer is insoluble the drug was more restrained in the ground extrudates than in the electrospun fibers. This state was followed by a quick burst as the pH rose to 7.4. EudFS, well-processed by electrospinning or melt extrusion, proved to be a promising matrix for oral drug delivery applications especially targeting the colon.

KW - Controlled drug delivery

KW - Electrospinning

KW - Eudragit® FS 100

KW - Extrusion

KW - Melt rheology

KW - Raman spectroscopy

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