Niosomes formulated from different nonionic surfactants (Span® 60, Brij® 72, Span® 80, or Eumulgin® B 2) with cholesterol (CH) molar ratios of 3:1 or 4:1 with respect to surfactant were prepared with different sumatriptan amount (10 and 15 mg) and stearylamine (SA). Thin-film hydration method was employed to produce the vesicles, and the time lapsed to hydrate the lipid film (1 or 24 h) was introduced as variable. These factors were selected as variables and their levels were introduced into two L18 orthogonal arrays. The aim was to optimize the manufacturing conditions by applying Taguchi methodology. Response variables were vesicle size, zeta potential (Z), and drug entrapment. From Taguchi analysis, drug concentration and the time until the hydration were the most influencing parameters on size, being the niosomes made with Span® 80 the smallest vesicles. The presence of SA into the vesicles had a relevant influence on Z values. All the factors except the surfactant-CH ratio had an influence on the encapsulation. Formulations were optimized by applying the marginal means methodology. Results obtained showed a good correlation between mean and signal-to-noise ratio parameters, indicating the feasibility of the robust methodology to optimize this formulation. Also, the extrusion process exerted a positive influence on the drug entrapment.
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