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.

Keywords: Controlled release; Electrospinning; Physical stability; Piroxicam; Polymeric nanofibers; Solid dispersion.