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

Abstract

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.

Electrospun PVP-Core/PHBV-Shell Fibers to Eliminate Tailing Off for an Improved Sustained Release of Curcumin

“…As a “brother” technology of electrospraying, electrospinning uses electrostatic field forces to fabricate continuous micro-/nanofibers. − In recent years, coaxial electrospinning, an “improved version” of traditional single-fluid electrospinning, has been developed and widely used in the preparation of functional materials. − The encapsulation efficiency and release characteristics of the drug will be improved when they attach to the surface of the carrier or are encapsulated inside. − Inspired by this concept, a series of drug-sustained release strategies have been realized by electrospinning medicine nanofibers …”

Recent and Relevant Methodology in the Advancement of Solid Dispersion

“…93 Edina Szabó, et al, developed amorphous solid dispersions (ASDs) of spironolactone and poly(vinylpyrrolidone-co-vinyl acetate) with drug-loaded electrospun (ES) and spray-dried (SD) materials from dichloromethane and ethanol-containing solutions. 94 BalázsDémuth, et al, developed solid dispersions of itraconazole [ITR] containing polyvinylpyrrolidone-vinyl acetate. Magnesium stearate acted as a nucleation promoting agent.…”

Flux-Based Formulation Development—A Proof of Concept Study

“…During the manufacturing, nano-/microfibers are created from a viscous polymer solution containing an API using the driving force of an electrostatic field. This method has several advantages: it is a gentle method for the preparation of solid formulations of the various bioactive agent [14,15]; it can be a part of continuous manufacturing [16,17]; and compared to the spray-drying, the amorphous structure is more homogenous and stable as a result of electrostatic forces which lead to more effective solvent evaporation [18,19]. Polymer additives used for electrospinning are responsible for making the API's supersaturation last longer in solution, but these excipients generally do not modify the equilibrium crystalline solubility of API.…”