Dissolution improvement of electrospun nanofiber-based solid dispersions for acetaminophen

Abstract

The objective of the present investigation was to prepare novel solid dispersions (SDs) of poorly water-soluble drugs with special microstructural characteristics using electrospinning process. With the hydrophilic polymer polyvinylpyrrolidone as the filament-forming polymer and acetaminophen (APAP) as the poorly water-soluble drug model, SDs having a continuous web structure, and in the form of non-woven nanofiber membranes, were successfully prepared. The electrospun nanofiber-based SDs were compared with those prepared from three traditional SD processes such as freeze-drying, vacuum drying, and heating drying. The surface morphologies, the drug physical status, and the drug-polymer interactions were investigated by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and attenuated total reflectance Fourier transform infrared. In vitro dissolution tests demonstrated that the electrospun nanofibers released 93.8% of the APAP content in the first 2 minutes and that the dissolution rates of APAP from the different SDs had the following order: electrospun membrane > vacuum-dried membrane approximately freeze-dried membrane > heat-dried membrane. Electrospun nanofiber-based SDs showed markedly better dissolution-improving effects than the other SDs, mainly due to their huge surface area, high porosity resulting from web structure, and the more homogeneous distribution of APAP in the nanofiber matrix.

Fig. 1

SEM images of membranes. Magnifications are ×2,000 for all the images, and ×10,000 for the further magnified images in the upper right-hand corners. Images are of membranes formed by a heat-drying, b vacuum drying, c freeze-drying, and d electrospinning

Fig. 2

DSC thermograms, representing the first scan with a scan rate of 10°C/min, of membranes formed by a freeze-drying, b vacuum drying, c heat-drying, d electrospinning, and of e pure APAP, and f PVP K90

Fig. 3

X-ray diffraction patterns using a slit detector and with a scan rate of 10°/min of a APAP, b PVP K90, and membranes prepared by c electrospinning, d heat-drying, e vacuum drying, and f freeze-drying

Fig. 4

ATR-FTIR spectra: membranes prepared by a vacuum drying, b freeze-drying, c heat-drying, d electrospinning, e PVP K90, f APAP

Fig. 5

Hydrogen bonding: a APAP–APAP, b APAP–PVP K90

Fig. 6

APAP dissolution profiles from membranes prepared by a electrospinning, b freeze-drying, c vacuum drying, d heat-drying, e profile of pure APAP particles