Sildenafil sublingual spray formulation

1. A sublingual spray formulation comprising:

a. about 0.1% w/w to about 30% w/w sildenafil;

b. about 5% w/w to about 95% w/w of a pharmaceutically acceptable cosolvent selected from the group consisting of an alcohol, dehydrated alcohol, a glycol, a medium chain triglyceride and binary, ternary, or quaternary mixtures thereof;

c. about 1% w/w to about 40% w/w of malic acid; and

d. about 5% w/w to about 40% w/w water.

2. The formulation of claim 1 wherein the alcohol is dehydrated alcohol.

3. The formulation of claim 1 wherein the sildenafil is a pharmaceutically acceptable salt selected from the group consisting of citrate, hydrochloride, halide, sulfate, phosphate, acetate, maleate, succinate, ascorbate, carbonate, mesylate and lactate.

4. The formulation of claim 1 further comprising a pharmaceutically acceptable solubilizer and/or surfactant and/or stabilizer; and/or permeation enhancer; and/or antioxidant; and/or preservative; and/or flavoring agent; and/or sweetener.

5. The formulation of claim 4 wherein

a. the solubilizer and/or surfactant and/or stabilizer is selected from the group consisting of polysorbate, sorbitan, polyvinylpyrrolidine, sodium lauryl sulfate, poloxamer, cremophor, lactic acid and cyclodextrin;

b. the permeation enhancer is selected from the group consisting of oleic acid, citric acid, cetylpyridinium chloride, glyceryl oleate, menthol, L-lysine, polysorbate-20, polysorbate-80, sodium lauryl sulfate, sodium desoxycholate and a combination thereof;

c. the antioxidant is selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), methionine, ascorbic acid, sodium ascorbate, sodium thiosulfate, sodium bisulfite, sodium metabisulfite, ascorbyl palmitate, thioglycerol, and a combination thereof;

d. the preservative is selected from the group consisting of methyl paraben, propyl paraben, sodium benzoate, benzoic acid, sorbic acid, and a combination thereof;

e. the flavoring agent is selected from the group consisting of peppermint oil, blackberry, strawberry, raspberry, grape, lemon, lemon mint, cinnamon, menthol, and a combination thereof; or

f. the sweetener is selected from the group consisting of sucralose, sucrose, sorbitol, fructose, acesulfame K, aspartame, sodium saccharin, stevia, xylitol and ammonium salt of Glycyrrhizic Acid, and a combination thereof.

6. The formulation of claim 1 wherein administration results in a mean C max of about 380 to about 550 ng/ml, T max of about 50 to about 110 minutes, and mean AUC0-t of about 50,000 ng·min/mL to about 150,000 ng·min/mL.

7. The formulation of claim 1 wherein administration results in a mean C max of about 450 to about 500 ng/ml, T max of about 80 to about 90 minutes, and mean AUC0-t of about 90,000 ng·min/mL to about 120,000 ng·min/mL.

8. A method of treating pulmonary arterial hypertension in a human comprising administering the formulation of claim 1 to a patient in need thereof.

9. A method of treating sexual dysfunction in men comprising administering the formulation of claim 1 to a patient in need thereof.

10. A sublingual spray formulation comprising about 0.1% w/w to about 30% w/w sildenafil, about 5% w/w to about 40% w/w water, about 10% w/w to about 40% w/w denatured alcohol, and about 1% w/w to about 40% w/w malic acid.

11. The formulation of claim 10 wherein the formulation is propellant free.

12. The formulation of claim 10 comprising about 10% w/w to about 25% w/w sildenafil, about 20% w/w to about 35% w/w water, about 15% w/w to about 30% w/w denatured alcohol, and about 5% w/w to about 35% w/w malic acid.

13. The formulation of claim 12 further comprising about 0.05% w/w to about 0.20% w/w sweetener, about 0.005% w/w to about 1% w/w Glycyrrhizic Acid as the ammonium salt, and about 0.05% w/w to about 0.20% w/w of a flavoring agent selected from the group consisting of peppermint oil and strawberry.

14. A sublingual spray formulation comprising:

a. about 14% w/w to about 21% w/w sildenafil;

b. about 20% w/w to about 25% w/w dehydrated alcohol;

c. about 25% w/w to about 35% w/w malic acid;

d. about 0.5% w/w to about 1.0% w/w sweetener;

e. about 0.001% w/w to about 0.1% w/w ammonium salt form of Glycyrrhizic Acid;

f. about 0.10% w/w about 0.20% w/w flavoring agent; and

g. about 25% w/w to about 30% w/w water.