*2.12. Studies for Stability*

When the nanoemulgel formulations were centrifuged, no drug precipitation or phase separation was detected, indicating that the produced nanoemulgel was physically stable. Although these were exposed to thaw or freeze cycles, they did not exhibit symptoms of cracks or breaks. The findings of stability investigations demonstrated that nanoemulgels remain transparent, even 3 months later at different exposed temperatures such as 25 ◦C ± 2 ◦C, 37 ◦C ± 0.1 ◦C, along with 4 ± 0.2 ◦C. Even during stability investigation, each of the formulated mixtures was observed to be stable in terms of pH (6.8), transparency, the content of oil, and separation of phases. The increased viscosity of nanoemulgel may potentially limit Brownian mobility. *Gels* **2022**, *8*, x FOR PEER REVIEW 12 of 21

> **Table 2.** Dermatokinetic study chart. **Table 2.** Dermatokinetic study chart.


**Figure 9.** Images of CLSM within the perpendicular cross‐section of optimal skin surface of rats. **Figure 9.** Images of CLSM within the perpendicular cross-section of optimal skin surface of rats.

**Figure 10.** (**a**) Effect of Babchi oil nanoemulgel on epidermis concentration; (**b**) Effect of Babchi oil nanoemulgel on dermis concentration. **Figure 10.** (**a**) Effect of Babchi oil nanoemulgel on epidermis concentration; (**b**) Effect of Babchi oil nanoemulgel on dermis concentration.

*2.12. Studies for Stability* When the nanoemulgel formulations were centrifuged, no drug precipitation or phase separation was detected, indicating that the produced nanoemulgel was physically stable. Although these were exposed to thaw or freeze cycles, they did not exhibit symp‐ toms of cracks or breaks. The findings of stability investigations demonstrated that nanoemulgels remain transparent, even 3 months later at different exposed temperatures such as 25 °C ± 2 °C, 37 °C ± 0.1 °C, along with 4 ± 0.2 °C. Even during stability investiga‐ Nanoemulgels have great capacities for solubilization and for boosting permeability; due to this, nanoemulgel was used as a vehicle for distributing drug transdermally [28]. Aside from these facts, a topical approach for administration provides the opportunity to avoid the issues related to persistent oral dosing. The innovative techniques of nanoemulgel composed of combinations of aqueous and gel-based, surfactant and co-surfactants gels along with oil create multiple components for the drug loading system. Therefore, the nanoemulsions are created by determining the range of concentrations of each component. The size of the droplet, the conductance of the nanoemulsion, viscosity, and structural

morphology were developed and optimized. Images observed through the TEM indicated a round shape. The formulations observed were in the range of 10–100 nm nano size. PDI value showed the droplets to be of consistent size throughout the formulations. O/W structure was observed which validated the nanoemulsion for its increased values of conductivity. Values obtained for viscosity were increased which made it suitable for skin application. The nanoemulsions that were induced within the base of the gel resulted in the formulation of the nanoemulgel. These nanoemulgel formulations had minimal loss of Babchi oil molecules. The pH of the formulation was similar to the skin pH, and therefore the formulation presented to be of minimal irritation in nature. The drag and slip phenomena with increased diameters were observed when formulations spreadability was checked. Higher viscosity content was observed along with a pseudoplastic manner when produced by the rheogram which ensured the flow would not occur within the system that was developed. In addition, collapsible tube and container filling would have required an ejection yield value [29].

The nanoemulgels formulated underwent studies for permeability in which Babchi oil nanoemulgel proved to be of higher significance as the permeation observed was higher and the components of the formulation correlated with each other. When the co-surfactant was reduced and the content of oil was increased, the permeability of the formulation was observed to be greater. Babchi oil and its permeability to penetrate the lipid bilayers of the skin occur due to the synergistic effect as it disrupts the order and improvises the thermodynamic effect of the formulation due to lesser concentration of surfactant in the skin [30]. Through this study, we also observed the co-surfactant effect when used as an enhancer for permeation when compared with the formulations that were optimized and those that were prepared without the usage of co-surfactants as the amount of drug permeation was low cumulatively during the flux. It was also observed that retention of formulation on the skin was improved along with the lag time. In comparison with the parameters for permeability, the optimized Babchi oil nanoemulgel had increased permeation of drug amount along with the flux and ratio for enhancement and high retention by the skin than the other plain and marketed formulations. The formulation's AUC was higher in the epidermis, indicating improved formulation absorption and flow ability.

In this study, the nanoemulgel formulated presented with good potential for permeation without any induction of chemically synthesized enhancers. This reduced the cause of skin irritations and hence, the novelty of the study lies here because the constituents such as surfactant, co-surfactant, and oil that are present in the nanoemulgel act as enhancers for permeation. Studies for stability were performed at the refrigerator and normal temperatures which indicated the Babchi oil formulation was stable and there were no observed changes in pH or the content of the components in the formulation. These factors during the study provided an improved illustration of drug stability and the effect of Babchi oil. Therefore, this study provides sufficient data to provide evidence for the use of Babchi oil nanoemulgel in the treatment use of psoriasis.

### **3. Conclusions**

Babchi oil nanoemulgel has appropriate viscosity and was recently created for transdermal administration. The interaction between skin and nanoemulgels influences the rhamnolipid with incredibly precise penetration and enhances its potential, contributing significantly to drug absorption through the skin. In comparison to conventional pharmaceuticals, this Babchi oil-modified nanoemulgel demonstrated a significant improvement in drug penetration, showing that these nanoemulsion systems are possible carriers or vehicles for surrogate Babchi oil delivery.

### **4. Materials and Methods**

### *4.1. Materials*

Babchi oil and rhamnolipid along with Propylene glycol was obtained from Sigma Merck. Other materials such as ethanol and required chemicals were also purchased from Sigma Merck. The reagents used in the study were analytically graded.
