Oral soluble film containing sildenafil citrate

1. An oral soluble film, comprising:

(a) 36±7 wt. % sildenafil citrate;

(b) 30±6 wt. % binder comprising:

(i) polyvinyl alcohol (PVA);

(ii) polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer; and

(iii) silicon dioxide;

(c) 5.45±1 wt. % filler comprising microcrystalline cellulose (MCC);

(d) 6.44±1.25 wt. % flavoring agent comprising peppermint flavoring;

(e) 12±2.5 wt. % plasticizer comprising glycerin;

(f) 10±2 wt. % sweetening agent comprising sucralose and acesulfame potassium (ACE-K);

(g) 0.01±0.002 wt. % coloring agent comprising FD&C Blue 1;

(h) 0.10±0.02 wt. % preservative comprising sodium benzoate; and

(i) solvent comprising water.

2. An oral soluble film comprising:

(a) 70.24±7 mg sildenafil citrate;

(b) 58.53±12 mg binder comprising:

(i) polyvinyl alcohol (PVA);

(ii) polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer; and

(iii) silicon dioxide;

(c) 10.63±2 mg filler comprising microcrystalline cellulose (MCC);

(d) 12.56±2.5 mg flavoring agent comprising peppermint flavoring;

(e) 23.41±5 mg plasticizer comprising glycerin;

(f) 19.5±4 mg sweetening agent comprising sucralose and acesulfame potassium (ACE-K);

(g) 0.02±0.004 mg coloring agent comprising FD&C Blue 1;

(h) 0.20±0.04 mg preservative comprising sodium benzoate; and

(i) 9.76±2.25 mg water;

wherein,

the oral soluble film is configured as a unit dose;

the oral soluble film has a mass of 205±20 mg;

the oral soluble film has a thickness of 0.35±0.06 mm; and

upon contact with an oral mucosal surface, the oral soluble film dissolves within 60 seconds.

3. The oral soluble film of claim 2 , having a mass of 205±15 mg and which dissolves within 45 seconds upon contact with an oral mucosal surface.

4. A method of treating erectile dysfunction (ED) in a male subject, the method comprising orally administering the oral soluble film of claim 2 to a male subject in need thereof.

5. The method of claim 4 , wherein the oral administration comprises at least one of enteral delivery of sildenafil, transmucosal delivery of sildenafil, sublingual delivery of sildenafil, and buccal delivery of sildenafil; wherein the sildenafil is delivered as the free base or as the citrate salt.

6. The method of claim 4 , wherein the oral soluble film is administered to a male subject 30 minutes to 4 hours before sexual activity.

7. The method of claim 4 , wherein the oral soluble film is placed on the top of the tongue of the male subject.

8. The method of claim 4 , wherein the oral soluble film is orally administered to the male subject in the absence of water or beverage.

9. The method of claim 4 , wherein upon administration of sildenafil citrate equivalent to 50 mg of sildenafil, under fasted conditions with water, the oral soluble film exhibits a single-dose administration pharmacokinetic (PK) profile that comprises:

C MAX (ng/mL) of 396.227±105.035;

AUC 0→t (hr*ng/mL) of 1,426.893±520.565;

AUC 0→inf (hr*ng/mL) of 1,524.433±592.798;

T MAX (hr) of 1.088±0.466;

T 1/2 (hr) of 3.783±1.769; and

K EL (1/hr) of 0.211±0.068.

10. The method of claim 4 , having a maximum dosing frequency of once per day.

11. The method of claim 4 , wherein the male subject is at least 18 years old.

12. The oral soluble film of claim 1 , configured as a unit dose, wherein the oral soluble film:

(a) has a mass of 200±20 mg;

(b) has a thickness of 0.35±0.06 mm;

(c) has a water content of 4±1.5 wt. %; and

(d) dissolves within 60 seconds upon contact with an oral mucosal surface.

13. The oral soluble film of claim 1 , configured as a unit dose, having a mass of 205±15 mg, and which dissolves within 45 seconds upon contact with an oral mucosal surface.

14. A method of treating erectile dysfunction (ED) in a male subject, the method comprising orally administering the oral soluble film of claim 1 , configured as a unit dose, to a male subject in need thereof.

15. The method of claim 14 , wherein the oral administration comprises at least one of enteral delivery of sildenafil, transmucosal delivery of sildenafil, sublingual delivery of sildenafil, and buccal delivery of sildenafil; wherein the sildenafil is delivered as the free base or as the citrate salt.

16. The method of claim 14 , wherein the oral soluble film is administered to a male subject 30 minutes to 4 hours before sexual activity.

17. The method of claim 14 , wherein the oral soluble film is placed on the top of the tongue of the male subject.

18. The method of claim 14 , wherein the oral soluble film is orally administered to the male subject in the absence of water or beverage.

19. The method of claim 14 , wherein upon administration of sildenafil citrate equivalent to 50 mg of sildenafil, under fasted conditions with water, the oral soluble film exhibits a single-dose administration pharmacokinetic (PK) profile that comprises:

C MAX (ng/mL) of 396.227±105.035;

AUC 0→t (hr*ng/mL) of 1,426.893±520.565;

AUC 0→inf (hr*ng/mL) of 1,524.433±592.798;

T MAX (hr) of 1.088±0.466;

T 1/2 (hr) of 3.783±1.769; and

K EL (1/hr) of 0.211±0.068.

20. The method of claim 14 , having a maximum dosing frequency of once per day.

21. The method of claim 14 , wherein the male subject is at least 18 years old.

22. The oral soluble film of claim 1 , configured as a bulk roll.

23. The oral soluble film of claim 1 , having a water content of 4±1.5 wt. %.

24. The oral soluble film of claim 1 , which is manufactured from non-micronized sildenafil citrate having the following particle size distribution (PSD):

the percentage of particles smaller than 2 μm is 10%;

the percentage of particles smaller than 5 μm is 50%; and

the percentage of particles smaller than 35 μm is 90%.

25. The oral soluble film of claim 2 , wherein the variation of sildenafil citrate between two equally sized unit dosages is less than 5 wt. %.