Continuous preparation of vitamin E nanoemulsions via a novel ultrasonic tube-in-tube reactor: Critical factors impacting physical and chemical stability

Ultrasonic emulsification frequently serves to prepare nanoemulsions containing active ingredients, including Vitamin E (VE), which can be degraded by Reactive Oxygen Species (ROS) generated during conventional ultrasonication. To address this issue, VE nanoemulsions were continuously prepared using a novel temperature-controlled ultrasonic tube-in-tube reactor (USTIT). Effects of formulation and process parameters on physical and chemical stability were systematically investigated. The mixing surfactant of Tween-80/Span-80 produced smaller, more stable, and uniform droplets (135 nm), remaining stable for 100 days. As the aqueous to oil (A/O) ratio increased, the droplet sizes decreased significantly, and the VE retention increased. With antioxidant Ascorbyl Palmitate (AP), the VE half-life reached 862 days at an A/O ratio of 15/1, significantly enhancing VE stability at room temperature. Moreover, VE degradation kinetics changed from first-order to second-order, leading to more persistent protection of VE by AP. In addition, lower ultrasonic power, higher flow rate, and higher temperature significantly reduced ROS yield and VE degradation. Based on the accelerating degradation kinetics of VE during a 60 °C holding period, VE nanoemulsions with AP, prepared at 45 W of ultrasonic power, 3 mL/min of flow rate, and at 50 °C, exhibited a long VE half-life of 205 h due to uniform ultrasonic energy distribution, and controllable residence time and temperature. In contrast, the VE half-life only reached 92.6 h by a conventional ultrasonic probe and 170.1 h by an ultrasonic bath. Therefore, the USTIT process provides a foundation for the continuous, stable preparation of high-value lipid-soluble bioactive nanoemulsions.