Nanoemulsion, method for its preparation and use

1. A pharmaceutical formulation for the administration of melatonin in the form of a nanoemulsion, said nanoemulsion consisting of an aqueous phase and a lipid phase, said aqueous phase comprising a base, said lipid phase comprising a polyoxyethylene sorbitan ester, the said aqueous phase or lipid phase, or both, further comprising ascorbyl palmitate, wherein said nanoemulsion comprises melatonin as an active agent in an amount from 0.1% to 10% w/t, wherein in the nanoemulsion the emulsifying components consist of polyoxyethylene sorbitan ester and ascorbyl palmitate as the only emulsifying components, wherein in the nanoemulsion ascorbyl palmitate is present in an amount from 0.3 to 2% by weight and said polyoxyethylene sorbitan ester is present in an amount from 0.2 to 10% by weight and wherein said nanoemulsion comprises micelle sizes from 20 to 900 nm.

2. The pharmaceutical formulation of claim 1 , wherein both the aqueous phase and the lipid phase comprise ascorbyl palmitate.

3. The pharmaceutical formulation of claim 1 , wherein the polyoxyethylene sorbitan ester is selected from the group consisting of: polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80 and any combination thereof.

4. The pharmaceutical formulation of claim 1 , wherein the micelle size is from 20 to 200 nm.

5. The pharmaceutical formulation of claim 1 , wherein the base is selected from the group consisting of: L-arginine, L-lysine, a peptide, aminomethylpropanol, an alkaline metal hydrate, an alkaline earth metal hydrate, and any combination thereof.

6. The pharmaceutical formulation of claim 1 , wherein the aqueous phase further comprises one or more preserving agents selected from the group consisting of: potassium sorbate, sodium benzoate, parabens, and any combination thereof.

7. The pharmaceutical formulation of claim 1 , wherein the lipid phase comprises one or more lipids selected from the group consisting of: coconut oil, wheat germ oil, sunflower oil, olive oil, a medium-chain triglyceride, and any combination thereof.

8. The pharmaceutical formulation of claim 7 , wherein the one or more lipids are present in an amount from 0.1 to 10% w/w.

9. The pharmaceutical formulation of claim 1 , further comprising one or more polyols in an amount from 0.1 to 40% w/w.

10. The pharmaceutical formulation of claim 9 , wherein the one or more polyols are selected from the group consisting of: glycerine, propylene glycol, sorbitol, mannitol, fructose, sucrose, glucose, trehalose, and honey.

11. The pharmaceutical formulation of claim 1 , further comprising active agents selected from the group consisting of: flavonoids, flavones, flavanones, isoflavones, essential oils, terpenes, plant saponins, liposoluble vitamins, vitamin cofactors, enzyme cofactors, amino acids, oligopeptides, peptides, saturated fatty acids, unsaturated fatty acids, and any combination thereof.

12. The pharmaceutical formulation of claim 1 , having a pH from 3 to 7.

13. The pharmaceutical formulation of claim 1 , further comprising an acidic pH chitosan solution.

14. A method for making the pharmaceutical formulation of claim 1 , comprising the following sequential steps:

(a) preparing an aqueous phase comprising a base and a lipid phase comprising a lipid and a polyoxyethylene sorbitan ester, wherein the aqueous phase or the lipid phase, or both, further comprise ascorbyl palmitate;

(b) heating the aqueous and lipid phases at a temperature from 30 to 80° C.;

(c) pouring out the aqueous phase into the lipid phase under mechanical stirring, so as to obtain the nanoemulsion;

(d) bringing the nanoemulsion to room temperature, and

(e) dispersing melatonin as an active agent into the nanoemulsion by mechanical stirring,

wherein polyoxyethylene sorbitan ester and ascorbyl palmitate are included as the only emulsifying components.