Preparation and characterization of lapatinib-loaded PVP nanofiber amorphous solid dispersion by electrospinning

Abstract

Lapatinib-loaded polyvinylpyrrolidone-based nanofibrous solid dispersions were prepared by electrospinning in order to enhance the aqueous solubility and dissolution rate of the anticancer drug. The prepared nanofibers were characterized by smooth-surfaced, homogenous filaments with average diameters of 462±160 nm determined by scanning electron microscopy. The crystalline to amorphous transition of the active ingredient was confirmed by differential scanning calorimetry, while Raman spectroscopy showed that amorphous lapatinib was uniformly distributed in the fibrous structures. Gas chromatographic analyses revealed that residual solvents in the nanofiber mats were below the ICH Guideline Q3C recommended limits, namely ethanol 10.9±2.3 ppm (recommended limit 5000 ppm) and dimethyl formamide 780±56 ppm (recommended limit 880 ppm). Determination of drug content and in vitro dissolution studies were performed in order to observe the influence of electrospinning on the drug release characteristics of the product obtained. The lapatinib content in the nanofibers were measured to be 16.76±0.11 w/w%, whereas the dissolution study at pH 6.8 indicated a rapid disintegration of the nanofibrous mats, releasing ~70% of the drug loading under 5 minutes compared to the ~0.05% dissolution of the neat lapatinib ditosylate. The results confirm the applicability of electrospinning for the improvement of physicochemical characteristics of the poorly bioavailable anticancer agent.

Keywords

• processing technologies
• lapatinib ditosylate
• dissolution
• electrospinning
• solid dispersion