Oral soluble film containing sildenafil citrate

Abstract

The present invention relates to an oral soluble film (OSF), methods of orally administering the same, and methods of manufacturing the same. The oral soluble film includes sildenafil citrate, and can further include a binder, filler, flavoring agent, plasticizer, sweetening agent, preservative, solvent, and optionally coloring agent. The active ingredient and excipients can be provided and present in an amount effective to achieve desired physical and performance characteristics of the OSF.

1 . An oral soluble film, comprising:
 (a) sildenafil citrate;   (b) binder comprising:
 (i) polyvinyl alcohol (PVA); 
 (ii) polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer; and 
 (iii) silicon dioxide; 
   (c) filler comprising microcrystalline cellulose (MCC);   (d) flavoring agent comprising peppermint flavoring;   (e) plasticizer comprising glycerin;   (f) sweetening agent comprising sucralose and acesulfame potassium (ACE-K);   (g) coloring agent comprising FD&C Blue 1;   (h) preservative comprising sodium benzoate; and   (i) solvent comprising water.   
     
     
         2 . 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.   
     
     
         3 . 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. 
     
     
         4 . The oral soluble film of  claim 1 , wherein the sildenafil citrate is present in an amount of 0.24±0.06 mg/mm3. 
     
     
         5 . The oral soluble film of  claim 1 , configured as a unit dose, exhibiting a dissolution (USP apparatus: 1 (basket); media: 0.01 N HCl; volume: 900-ml; temperature: 37±0.5° C.; RPM: 100; sampling: 5, 10, 15, 30, 45, 60 min) of (i) at least 90 wt. % at 5 minutes and (ii) 100 wt. % release at 10 minutes. 
     
     
         6 . The oral soluble film of  claim 1 , configured as a unit dose, exhibiting a stability, such that at least 90 wt. % of the sildenafil citrate remains in the oral dissolvable film, under stability conditions of 25±2° C., relative humidity (RH) 60±5%, over a period of time of >6 months. 
     
     
         7 . The oral soluble film of  claim 1 , wherein the binder comprises Kollicoat® Protect, which additionally functions as a film-coating agent, disintegrating agent, taste masking agent, emulsifier, anti-caking agent, to increase tensile strength of the oral soluble film, to increase elongation of the oral soluble film, or any combination thereof. 
     
     
         8 . The oral soluble film of  claim 1 , wherein the filler comprises microcrystalline cellulose, which additionally functions as a binder, anti-caking agent, emulsifier, bulking agent, viscosity increasing agent, or any combination thereof. 
     
     
         9 . The oral soluble film of  claim 1 , wherein the flavoring agent comprises peppermint flavoring, which additionally functions as a taste masking agent, permeation enhancer, or a combination thereof. 
     
     
         10 . The oral soluble film of  claim 1 , wherein the plasticizer comprises glycerin, which additionally functions as a sweetener, humectant, solvent, thickening agent, lubricant, or any combination thereof. 
     
     
         11 . 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. 
     
     
         12 . The method of  claim 11 , 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. 
     
     
         13 . The method of  claim 11 , wherein the oral soluble film is administered to a male subject 30 minutes to 4 hours before sexual activity. 
     
     
         14 . The method of  claim 11 , wherein the oral soluble film is placed on the top of the tongue of the male subject. 
     
     
         15 . The method of  claim 11 , wherein the oral soluble film is orally administered to the male subject in the absence of water or beverage. 
     
     
         16 . The method of  claim 11 , wherein the oral soluble film is orally administered to the male subject with water or beverage. 
     
     
         17 . The method of  claim 11 , wherein the male subject is at least 18 years old. 
     
     
         18 . The method of  claim 11 , wherein the sildenafil citrate is administered in an amount equivalent to 50±5 mg of sildenafil, as the free base. 
     
     
         19 . The method of  claim 11 , wherein the sildenafil citrate is administered in an amount equivalent to 50 mg of sildenafil, as the free base. 
     
     
         20 . The method of  claim 11 , wherein the oral soluble film is orally administered to treat erectile dysfunction (ED), and the male subject achieves an erection in 12-70 minutes after the oral administration.