Comparison of Amorphous Solid Dispersions of Spironolactone Prepared by Spray Drying and Electrospinning: The Influence of the Preparation Method on the Dissolution Properties

[Image: see text] This research aimed to compare two solvent-based methods for the preparation of amorphous solid dispersions (ASDs) made up of poorly soluble spironolactone and poly(vinylpyrrolidone-co-vinyl acetate). The same apparatus was used to produce, in continuous mode, drug-loaded electrospun (ES) and spray-dried (SD) materials from dichloromethane and ethanol-containing solutions. The main differences between the two preparation methods were the concentration of the solution and application of high voltage. During electrospinning, a solution with a higher concentration and high voltage was used to form a fibrous product. In contrast, a dilute solution and no electrostatic force were applied during spray drying. Both ASD products showed an amorphous structure according to differential scanning calorimetry and X-ray powder diffraction results. However, the dissolution of the SD sample was not complete, while the ES sample exhibited close to 100% dissolution. The polarized microscopy images and Raman microscopy mapping of the samples highlighted that the SD particles contained crystalline traces, which can initiate precipitation during dissolution. Investigation of the dissolution media with a borescope made the precipitated particles visible while Raman spectroscopy measurements confirmed the appearance of the crystalline active pharmaceutical ingredient. To explain the micro-morphological differences, the shape and size of the prepared samples, the evaporation rate of residual solvents, and the influence of the electrostatic field during the preparation of ASDs had to be considered. This study demonstrated that the investigated factors have a great influence on the dissolution of the ASDs. Consequently, it is worth focusing on the selection of the appropriate ASD preparation method to avoid the deterioration of dissolution properties due to the presence of crystalline traces.