*4.5. Model Validation*

Two rivastigmine-loaded NLC formulations with the selected ratios of lipids and surfactants were produced under the most suitable instrumental parameters found for the ultrasound technique and the HPH method. The results of the observed responses were within the design space and close to the predicted values, which allowed for model validation (Table 5).

Regarding the observed responses in Table 5, other studies involving drug-loaded NLCs for nose-to-brain delivery have reported similar values for ZP, particle size, PDI, and EE. For example, Jain et al. optimized an artemether-loaded NLC for intranasal delivery with a particle size of 123.4 nm, ZP of −34.4 mV, and EE of 91.2% [99]. Gadhave et al. developed a teriflunomide-loaded NLC with a particle size of 99.8 nm, PDI of 0.35, ZP of −22.3 mV, and EE of 83.4% [31]. Madane and Mahajan prepared a curcumin-loaded NLC with a particle size of 146.8 nm, PDI of 0.18, EE of 90.86%, and ZP of −21.4 mV [33].


**Table 5.** Observed and predicted response values of the two optimized rivastigmine-loaded nanostructured lipid carriers (NLC) formulations.

Results presented as mean <sup>±</sup> SD (*<sup>n</sup>* <sup>=</sup> 3); <sup>1</sup> Z-Ave: mean particle size; <sup>2</sup> PDI: polydispersity index; <sup>3</sup> ZP: zeta potential; <sup>4</sup> EE: encapsulation efficiency.

*Pharmaceutics* **2020**, *12*, 599 16 of 27

**Figure 3.** The 3-D surface plots portraying the effect of the sonication amplitude and emulsification speed (rpm) on the size (Z-Ave (mean particle size); D50 (50% of particles size equal or lower to the given value) and D90 (90% of particles with size equal or lower to the given value)) (left: **A**–**C**), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) (right: **D**–**F**). **Figure 3.** The 3-D surface plots portraying the effect of the sonication amplitude and emulsification speed (rpm) on the size (Z-Ave (mean particle size); D50 (50% of particles size equal or lower to the given value) and D90 (90% of particles with size equal or lower to the given value)) (left: **A**–**C**), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) (right: **D**–**F**).
