Formation of drug-loaded nanoemulsions in stirred media mills

The feasibility of stirred media mills for the production of nanoemulsions loaded with active pharmaceutical ingredients (API) using plant oils as disperse phase and different types of the non-ionic emulsifier polysorbate is demonstrated. The influence of the emulsion formulation, namely oil type, surfactant and surfactant-to-oil-weight-ratio (SOR) on the product droplet size at constant stressing conditions is studied in detail. At similar stressing conditions and SOR, the type of the used plant oil and surfactant did not influence the product droplet size and the smallest achievable median droplet size was 20 nm. The API saturated oil phases and the pure oil phases exhibit similar viscosities, emulsification kinetics and final product droplet sizes, i.e. no influence of the API on the emulsification process could be identified. However, a strong dependency of the emulsion droplet size on the SOR has been observed. Moreover, very good long-term stabilities could be achieved for the obtained emulsions. A release test with fenofibrate-loaded peanut oil-polysorbate 80-water nanoemulsions showed remarkably fast drug distribution as compared to a formulation containing the same amount of the non-dissolved micronized drug.