title: Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs.
abstract: Electrospinning was introduced as a novel technique for preparing controlled-release (CR) amorphous solid dispersions (SD) and polymeric nanofibers of a poorly water-soluble drug. Piroxicam (PRX) was used as a low-dose poorly-soluble drug and hydroxypropyl methylcellulose (HPMC) as an amorphous-state stabilising carrier polymer in nanofibers. Raman spectroscopy, X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used in the physical characterisation of the CR-SD nanofibers. Special attention was paid on the effects of a polymer and solvent system on the solid-state properties and physical stability of nanofibers. The average dry diameter of the electrospun CR-SD nanofibers ranged from 400 to 600 nm (SEM). PRX existed in amorphous form in the nanofibers immediately after fabrication and after a short-term (3-month) aging at low temperature (6-8 °C/0% RH) and ambient room temperature (22 °C/0% RH). At higher temperature and humidity (30 °C/85% RH), however, amorphous PRX in the nanofibers tended to slowly recrystallise to PRX form III. The electrospun CR-SD nanofibers exhibited a short lag-time, the absence of initial burst release and zero-order linear CR dissolution kinetics. In conclusion, electrospinning can be used to fabricate supersaturating CR-SD nanofibers of PRX and HPMC, and to stabilise the amorphous state of PRX.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: urve.paaver@ut.ee.
authors.forename: Urve
authors.initials: U
authors.lastname: Paaver
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: jyrki.heinamaki@ut.ee.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: ivo.laidmae@ut.ee.
authors.forename: Ivo
authors.initials: I
authors.lastname: Laidmäe
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: andres.lust@ut.ee.
authors.forename: Andres
authors.initials: A
authors.lastname: Lust
authors.affiliation: Institute of Physics, University of Tartu, Ravila 14c, 50411 Tartu, Estonia. Electronic address: jekaterina.kozlova@ut.ee.
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Kozlova
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: elensillaste@gmail.com.
authors.forename: Elen
authors.initials: E
authors.lastname: Sillaste
authors.affiliation: Institute of Ecology and Earth Sciences, University of Tartu, Ravila 14a, 50411 Tartu, Estonia. Electronic address: kalle.kirsimae@ut.ee.
authors.forename: Kalle
authors.initials: K
authors.lastname: Kirsimäe
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: peep.veski@ut.ee.
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. Electronic address: kkogermann@gmail.com.
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
mesh_terms: D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D008855:Microscopy, Electron, Scanning; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010894:Piroxicam / Q000008:administration & dosage / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D014867:Water; D010894:Piroxicam
keywords: Controlled release; Electrospinning; Physical stability; Piroxicam; Polymeric nanofibers; Solid dispersion