*2.8. Studies for Permeability of Skin*

Babchi oil nanoemulgel formulation had higher drug profile transfer throughout the skin of rats with *<sup>p</sup>* < 0.0001 and flux of 4.21 <sup>±</sup> 2.25 <sup>µ</sup>g/cm2/h compared to conventional formulation with the flux of 3.06 <sup>±</sup> 3.12 <sup>µ</sup>g/cm2/h. The presence of Babchi oil in the nanoemulgel system might contribute to the significant disparity in the percentage of drug distribution. The Babchi oil permeability was increased by enhancing the solubility of the surfactant during the formulation. Due to the compact design of the developed systems, they were capable of deeper penetrating the intrinsic layers of skin and resulting in greater absorption of the drug. In comparison to standard formulations, nanoemulgel was proven to improve penetration rates within deep layers of skin and also reduce lag time. The total amount of oil penetration, skin retention, flux, lag time, LAE, and enhancement ratio was determined.

**Figure 3.** *Cont*.

**Figure 3.** 3D Response surface graphs showing the effect of oil and Smix concentration on (**a**) Particle Size (nm), (**b**) Zeta Potential (mV) and (**c**) Entrapment Efficiency (%EE). **Figure 3.** 3D Response surface graphs showing the effect of oil and Smix concentration on (**a**) Particle Size (nm), (**b**) Zeta Potential (mV) and (**c**) Entrapment Efficiency (%EE). *Gels* **2022**, *8*, x FOR PEER REVIEW 8 of 21

**Figure 4.** Zeta potential data analysis, (**a**) phase–time graph of Babchi oil zeta potential, (**b**) total count of Babchi oil zeta potential distribution graph, (**c**) Babchi size distribution and intensity graph. **Figure 4.** Zeta potential data analysis, (**a**) phase–time graph of Babchi oil zeta potential, (**b**) total count of Babchi oil zeta potential distribution graph, (**c**) Babchi size distribution and intensity graph.

Babchi oil nanoemulgel formulation had higher drug profile transfer throughout the skin of rats with *p* < 0.0001 and flux of 4.21 ± 2.25 μg/cm2 /h compared to conventional

The nanoemulgel formulation was compared with the conventional formulation to observe the percentage of drug release in the epidermal layer. Figure 5 depicts the results obtained during the in vitro release study of the optimized nanoemulsion and its suspen‐ sion. It was observed that the percentage of release from the optimized nanoemulsion was greater than 81.26 in comparison to the suspension of 38.19. It was observed that Babchi oil nanoemulgel produced a higher percentage of drug release in comparison to the con‐ ventional formulation and constantly increased with time. The different models used for the analysis of in vitro release such as the zero‐order release model as depicted in Figure 6a produced higher effects and also increased with time. The y value taken was 0.0004 x + 0.2893 and the R2 value taken was 0.7464 for plotting the graph. The first order release model was plotted with a y value of −0.0005 x + 1.8667 and an R2 value of 0.9023 which is depicted in Figure 6b. It was observed that analysis with this model decreased the log percentage of the remaining drug with time. Figure 6c shows the Higuchi model shown with a y value of 0.0219 x + 0.0846 and an R2 value of 0.9185. It was observed that this analysis model increased the fraction of drug release with time. Finally, the Korsmeyer Peppas model was implemented with a y value of 0.5103 x + 0.4043 and an R2 value of

drug distribution. The Babchi oil permeability was increased by enhancing the solubility of the surfactant during the formulation. Due to the compact design of the developed sys‐ tems, they were capable of deeper penetrating the intrinsic layers of skin and resulting in greater absorption of the drug. In comparison to standard formulations, nanoemulgel was proven to improve penetration rates within deep layers of skin and also reduce lag time. The total amount of oil penetration, skin retention, flux, lag time, LAE, and enhancement

ratio was determined.

*2.9. In Vitro Release Studies*

*2.8. Studies for Permeability of Skin*


**Table 1.** Responses obtained using CCRD.

### *2.9. In Vitro Release Studies*

The nanoemulgel formulation was compared with the conventional formulation to observe the percentage of drug release in the epidermal layer. Figure 5 depicts the results obtained during the in vitro release study of the optimized nanoemulsion and its suspension. It was observed that the percentage of release from the optimized nanoemulsion was greater than 81.26 in comparison to the suspension of 38.19. It was observed that Babchi oil nanoemulgel produced a higher percentage of drug release in comparison to the conventional formulation and constantly increased with time. The different models used for the analysis of in vitro release such as the zero-order release model as depicted in Figure 6a produced higher effects and also increased with time. The y value taken was 0.0004x + 0.2893 and the R<sup>2</sup> value taken was 0.7464 for plotting the graph. The first order release model was plotted with a y value of <sup>−</sup>0.0005x + 1.8667 and an R<sup>2</sup> value of 0.9023 which is depicted in Figure 6b. It was observed that analysis with this model decreased the log percentage of the remaining drug with time. Figure 6c shows the Higuchi model shown with a y value of 0.0219x + 0.0846 and an R<sup>2</sup> value of 0.9185. It was observed that this analysis model increased the fraction of drug release with time. Finally, the Korsmeyer Peppas model was implemented with a y value of 0.5103x + 0.4043 and an R<sup>2</sup> value of 0.9414 and was plotted in Figure 6d. It was observed that Babchi oil nanoemulgel followed the Korsmeyer Peppas model and produced the most significant results of drug release with time. Higuchi model was considered the best with the Korsmeyer Peppas model producing the most potent diffusion. Figure 7 depicts the results obtained for studies of absorption (nM). The percentage of drug release by time graph of the nanoemulsion formulation was plotted and depicted in Figure 8.
