Polymer-free and polyvinylpirrolidone-based electrospun solid dosage forms for drug dissolution enhancement

Abstract

Fast-release nano- and microfibres of lipophilic spironolactone were prepared in a continuous manner by electrostatic spinning, in which the application of polyvinylpyrrolidone K90 as matrix polymer enabled formation of solid solutions. However, instead of the anticipated immediate drug release, temporary precipitation was observed. The polyvinylpyrrolidone web gelled immediately after wetting, hindering drug diffusion and aiding the crystallisation of the solvated amorphous spironolactone. These local supersaturations could be successfully avoided by using hydroxypropyl-β-cyclodextrin. The dependence of fibre diameter and dissolution rate on the complexing agent-polymer ratio was also studied. A small addition of hydroxypropyl-β-cyclodextrin proved enough for a dramatic release rate enhancement even in the case of high drug loaded formulations. Transmission Raman spectroscopy, differential scanning calorimetry and X-ray powder diffraction showed that the drug was totally amorphised during processing in all formulations. Polymer-free hydroxypropyl-β-cyclodextrin fibres containing spironolactone were also electrospun from an ethanolic solution, which is a new way of dissolution improvement in the case of poorly water-soluble drugs. This novel approach ensured nearly total drug release in a minute, making the system a suitable age-appropriate orally dissolving formulation.

Keywords: Cyclodextrins; Electrospinning; Immediate release; Nanofibers; Orally dissolving web; Transmission Raman spectroscopy.