Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics

Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs. In this work, the relation between the solvent evaporation rate and the kinetic stabilization of highly drug-loaded ASDs was investigated. Accordingly, thermal gravimetric analysis (TGA) was employed to study the evaporation kinetics of seven organic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen (NAP), on the evaporation behavior. At 10 °C below the boiling point of the respective solvent, methanol (MeOH) had the lowest evaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effect was more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNB increased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and the solvent or NAP and PVPVA, which was further investigated using Fourier transform-InfraRed (FT-IR) spectroscopy. Based on these findings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOH and DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP. Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited, demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantly determined by the API-polymer-solvent combination rather than the process parameters applied.

Publication year:2022

Accessibility:Open