Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Omega-3 fatty acid rich oils can enhance the solubility of lipophilic drugs without derailing the lipid profile. Careful optimization of oil and excipients is key to preparing self-nanoemulsifying drug delivery systems. Fish oil does not derail lipid profile and possesses beneficial effects of its own.

Optimization speeds up the formulation development process, saves resources and ensures stability for the intended application. Fish oil-based nanoformulations can not only enhance the bioavailability without disturbing the lipid profile, but may also synergize the therapeutic effect of the drug as shown by many clinical trials. This study can be employed for the optimization of different oil-based ternary systems, such as emulsions and SNEDDS, by determining the ratios of different formulation components and their effect on formulation characteristics.

Initial clues of starting ratios can be taken from the published literature. Researchers should be clear about which factors can affect the formulation characteristics. To begin, mix 100 milligrams of rosuvastatin separately in one milliliter of different omega-3 fatty acid rich oils, and one milliliter of surfactants and cosurfactants by vortexing for five minutes at a fixed speed of 2, 500 RPM.

After shaking, let the mixture settle for at least six hours at room temperature so that the undissolved drug is precipitated. Take 0.1 milliliters of supernatant by using a micro pipette and dilute up to one milliliter with methanol. Next, analyze by using a UV visible spectrophotometer at 242 nanometers to calculate the concentration.

To screen the surfactant and cosurfactants for miscibility with oil, mix the surfactant and the cosurfactant in a three to one ratio and add surfactant mixtures and oil in different ratios. After mixing, heat the surfactant mixtures up to 50 degrees Celsius to ensure homogenization. Take 0.1 milliliters from each mixture and dilute with 25 milliliters of distilled water in a glass test tube.

Invert the test tube. The number of inversions at which an emulsion is formed represents the emulsification efficacy and ease of emulsification. Measure the transparency by measuring the emulsion at 650 nanometers with a UV visible spectrophotometer using distilled water as a blank.

After mixing the surfactants and the cosurfactants in various volume ratios to form surfactant mixtures, add oil to the surfactant mixtures in separate vials at various volume ratios and mix by vortexing. Then add oil and surfactant mixtures in a 10 milliliter glass vial, and heat up to 50 degrees Celsius with constant stirring at 300 RPM for optimal mixing. After cooling the mixture to 37 degrees Celsius, transfer one milliliter from it to a 250 milliliter water beaker.

Select the flexible design by choosing no to a hard-to-change selection. Then select three independent variables as oil, surfactant, and cosurfactant, and run the software for optimization and screening. Select the higher and lower values as minus one, identifying the lowest variable value, whereas plus one depicts the highest value, and the mid-value depicts the middle value.

Observe the effect of these factors critically on dependent variables such as particle size, zeta potential, emulsification time, as well as entrapment efficiency. Record the responses to individual runs and fit them to linear 2F1 and quadratic models to ensure the best fitted model. Generate polynomial equations and utilize them to make the inference on the basis of the magnitude of the coefficient corresponding numerical signs.

Evaluate the best fitted data model by comparing adjusted R-square and predicted R-square values. Display data of polynomial regression as 3D plots. For thermodynamic stability studies, store the diluted SNEDDS at four degrees Celsius in a refrigerator.

And then transfer it to a 50 degree Celsius incubator. Examine the formulation for phase separation. To perform the dispersibility test for self-emulsification efficacy, add one milliliter of the formulation dropwise to 500 milliliters of double distilled water maintained at 37 degrees Celsius and 50 RPM.

Then note the time in which a clear homogenous emulsion is formed by visual inspection. Soak the dialysis membranes in the respective media solution for 24 hours before the drug dissolution assay to attain good integrity and activation. Fill the drug suspension and SNEDDS equivalent to 10 milligrams of rosuvastatin in the dialysis membrane.

Tie and place in separate beakers. After taking one milliliter of the sample at specific intervals, replenish the beaker with fresh media after each sample. Filter the drawn samples and analyze them by using a UV visible spectrophotometer at 242 nanometers.

The solubility of rosuvastatin was monitored, demonstrating that the highest solubility was exhibited by the fish oil, Tween 80, and Capryol PGMC, which were selected as the carrier oil, surfactant, and cosurfactant. The pseudoternary phase diagrams between different ratios of oil, surfactant, and cosurfactant were constructed. The results showed that the fish oil with surfactant at a one to three ratio has the highest curve area, indicating effective self-emulsification to form nanoemulsions.

3D plots represent the effect of surfactant and oil concentration on different parameters of SNEDDS. Increasing the concentration of oil and decreasing the surfactant, the particle size tends to increase. However, an increase in the cosurfactant concentration and the oil tends to decrease the particle size.

The negatively charged oil concentration increases the zeta potential linearly. At lower oil and surfactant concentrations, the potential was lower, but it reached a plateau at 0.20 milliliters of oil and 0.56 milliliters of surfactant. The surfactant and cosurfactant concentrations had a significant impact, while the oil concentration had a non-significant impact on emulsification time.

Cumulative drug release graphs show that fish oil SNEDDS are an effective delivery system of rosuvastatin with complete drug release in about 400 minutes. Whereas rosuvastatin release from suspension remained incomplete even after 800 minutes. For optimization, the selection of the independent factors is very important.

Obtain a clue of the middle value from the literature and then select the lower and higher levels. SNEDDS proposed in this study can effectively enhance bioavailability and may synergize the therapeutic action. Therefore, studies in animal models may be performed in the future.

Omega-3 fatty acids are used as supplements in the management of cardiovascular, neurological, inflammatory, and immunological diseases. Nanoformulations of omega-3 fatty acids have the potential to revolutionize their management.