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Emerging formulation technologies aimed to produce nanoemulsions with improved characteristics, such as stability are attractive endeavors; however, comparisons between competing technologies are lacking. In this study, two formulation techniques that employed ultrasound and microfluidic approaches, respectively, were examined for relative capacity to produce serviceable oil in water nanoemulsions, based on hempseed oil (HSO). The ultrasound method reached > 99.5% entrapment efficiency with nanoemulsions that had an average droplet size (Z-Ave) < 180 nm and polydispersity index (PDI) of 0.15 ± 0.04. Surfactant concentration (% w/v) was found to be a significant factor ( p  < 0.05) controlling the Z-Ave, PDI and zeta potential of these nanoparticles. On the other hand, the microfluidic approach produced smaller particles compared to ultrasonication, with good stability observed during storage at room temperature. The Z-Ave of < 62.0 nm was achieved for microfluidic nanoemulsions by adjusting the aqueous : organic flow rate ratio and total flow rate at 4:1 and 12 mL/min, respectively. Further analyses including a morphology examination, a simulated gastrointestinal release behavior study, transepithelial transport evaluations and a toxicity test, using a Caco2-cell model, were performed to assess the functionality of the prepared formulations. The results of this study conclude that both approaches of ultrasound and microfluidics have the capability to prepare an HSO-nanoemulsion formulation, with acceptable characteristics and stability for oral delivery applications.

Comparing microfluidics and ultrasonication as formulation methods for developing hempseed oil nanoemulsions for oral delivery applications