Spray drying and electrospraying are well-established drying processes that already have proven their value in the pharmaceutical field. However, there is currently still a lack of knowledge on the fundamentals of the particle formation process, thereby hampering fast and cost-effective particle engineering. To get a better understanding of how functional particles are formed with respect to process and formulation parameters, it is indispensable to offer a comprehensive overview of critical aspects of the droplet drying and particle formation process. This review therefore closely relates single droplet drying to pharmaceutical applications. Although excellent reviews exist of the different aspects, there is, to the best of our knowledge, no single review that describes all steps that one should consider when trying to engineer a certain type of particle morphology. The findings presented in this article have strengthened the predictive value of single droplet drying for pharmaceutical drying applications like spray drying and electrospraying. Continuous follow-up of the particle formation process in single droplet drying experiments hence allows optimization of manufacturing processes and particle engineering approaches and acceleration of process development.

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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.