Hydrophilic nanofibers as a supersaturating delivery system for carvedilol

Abstract

Polymer nanofibers represent a promising delivery system for poorly water-soluble drugs; however, their supersaturating potential has not been explored yet. Here, carvedilol-loaded nanofibers based on poly(ethyleneoxide) and on amphiphilic block copolymer poloxamer 407 were produced by electrospinning. These nanofibers provided high carvedilol loading and improved dissolution of carvedilol. Their dissolution resulted in a supersaturated system that was not stable, and thus to avoid carvedilol precipitation, hydroxypropyl methylcelluloses or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus) were additionally incorporated into the nanofibers. The morphology of the electrospun product was not affected by incorporation of carvedilol and the polymer precipitation inhibitors, as shown by scanning electron microscopy. The hydroxypropyl methylcelluloses were not effective polymer precipitation inhibitors for carvedilol. Incorporation of Soluplus significantly extended the duration of carvedilol supersaturation (>24 h) compared to the dissolution of nanofibers without Soluplus. Moreover, after 1 h of dissolution, incorporation of Soluplus into the nanofibers provided significantly higher carvedilol concentration (94.4 ± 2.5 μg/mL) compared to the nanofibers without Soluplus (32.7 ± 5.8 μg/mL), the polymer film (24.0 ± 2.2 μg/mL), and the physical mixture (3.3 ± 0.4 μg/mL). Thus, this study shows the great potential for hydrophilic nanofibers as a delivery system for sustained carvedilol supersaturation.

Keywords: Carvedilol; Electrospinning; Nanofibers; Poorly water-soluble drugs; Supersaturation.