Design, Optimization, Manufacture and Characterization of Milbemycin Oxime Nanoemulsions.

Despite the rapid development of nanoemulsions in recent years, no method has been established for the preparation of milbemycin oxime nanoemulsions. Milbemycin oxime is a widely used macrolide antibiotic in veterinary medicine, particularly for treating parasitic infections in animals such as dogs. However, its poor solubility in water limits its bioavailability and therapeutic efficacy. Developing a nanoemulsion formulation can enhance its solubility, stability, and bioavailability, offering a more effective treatment option. In this experiment, oil-in-water (O/W) milbemycin oxime nanoemulsions were successfully prepared by the phase inversion composition (PIC) method using ethyl butyrate as the oil phase, Tween-80 as the surfactant, and anhydrous ethanol as the co-surfactant. The region of O/W nanoemulsions was identified by constructing a pseudo-ternary phase diagram and, based on this, was screened by determining the droplet size, polydispersity coefficient, and zeta potential of each preparation. The finalized formulation had a 2:1 ratio of surfactant to co-surfactant and a 7:3 ratio of mixed surfactant to oil, and its droplet size, polydispersity index (PDI), and zeta potential were 12.140 ± 0.128 nm, 0.155 ± 0.015, and -4.947 ± 0.768 mV, respectively. Transmission electron microscopy confirmed the spherical uniform distribution of droplets, and the nanoemulsions passed thermodynamic stability tests. The in vitro release of milbemycin oxime nanoemulsions followed first-order kinetic equations. In conclusion, nanoemulsions are an interesting option for the delivery of poorly water-soluble molecules such as milbemycin oxime.