PDI, ZP, and EE

From the 3-D response surface plots (Figure 2D–F), it can be observed that as the emulsification speed and the number of HPH cycles change (increase or decrease), the values of PDI, ZP, and EE did not change significantly. PDI was around 0.21–0.26, indicating a narrow size distribution; ZP was in the range of −21 and −25 mV; EE ranged from 94% up to 98%. Thus, it was concluded that these parameters did not cause significant alterations in the rivastigmine-loaded NLC formulation. PDI, ZP, and EE From the 3-D response surface plots (Figure 2D–F), it can be observed that as the emulsification speed and the number of HPH cycles change (increase or decrease), the values of PDI, ZP, and EE did not change significantly. PDI was around 0.21–0.26, indicating a narrow size distribution; ZP was in the range of −21 and −25 mV; EE ranged from 94% up to 98%. Thus, it was concluded that these parameters did not cause significant alterations in the rivastigmine-loaded NLC formulation.

*Pharmaceutics* **2020**, *12*, 599 14 of 27

**Figure 2.** The 3-D surface plots portraying the effects of the number of high- pressure homogenization (HPH) cycles and emulsification speed (rpm) on the size (Z-Ave (mean particle size); D50 (50% of particles with 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 2.** The 3-D surface plots portraying the effects of the number of high- pressure homogenization (HPH) cycles and emulsification speed (rpm) on the size (Z-Ave (mean particle size); D50 (50% of particles with 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**).

4.4.2. Effects of Ultrasound Technique on Particles Size (Z-Ave, D50, and D90), PDI, ZP, and EE

The selected design fitted to CQAs when the 2-way interaction (linear quadratic) model was used. The observed and predicted values for CQAs using the ultrasound technique were the same, namely *R* <sup>2</sup> = 1 and *p* = 0.001 (Supplementary Data, Table S11).
