Rapidly infusing compositions for oral mucosal delivery and methods

Abstract

A rapidly infusing composition that includes (a) a pharmaceutically acceptable binder and/or excipient system containing gelatin, sugar alcohol (e.g., mannitol), and a flavorant and (b) an active therapeutic ingredient (ATI). Preferred rapidly infusing compositions are those formulated with a PDE5 inhibitor as the ATI. A method of administering an ATI such as a PDE5 inhibitor to a subject is also disclosed. The subject is administered the rapidly infusing composition via the oral mucosa to treat a condition responsive to inhibition of PDE5, for example, erectile dysfunction.

1 . A rapidly infusing composition, comprising:
 a pharmaceutically acceptable binder and/or excipient system comprising gelatin, a sugar alcohol, and a flavorant, and   a PDE 5  inhibitor.   
     
     
         2 . The rapidly infusing composition of  claim 1 , which is lyophilized. 
     
     
         3 . The rapidly infusing composition of  claim 1 , which has a disintegration time of approximately 1 to 30 seconds in deionized water maintained at 37° C.±2° C. 
     
     
         4 . The rapidly infusing composition of  claim 1 , which has a disintegration time of approximately 1 to 5 seconds in deionized water maintained at 37° C.±2° C. 
     
     
         5 . The rapidly infusing composition of  claim 1 , wherein the gelatin is present in the rapidly infusing composition in an amount of 10 to 35 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         6 . The rapidly infusing composition of  claim 1 , wherein the gelatin is mammalian gelatin. 
     
     
         7 . The rapidly infusing composition of  claim 6 , wherein the mammalian gelatin is bovine gelatin. 
     
     
         8 . The rapidly infusing composition of  claim 1 , wherein the sugar alcohol is present in the rapidly infusing composition in an amount of 5 to 35 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         9 . The rapidly infusing composition of  claim 1 , wherein the sugar alcohol is mannitol. 
     
     
         10 . The rapidly infusing composition of  claim 1 , wherein the flavorant is present in the rapidly infusing composition in an amount of 0.5 to 10 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         11 . The rapidly infusing composition of  claim 1 , wherein the flavorant comprises a mixture of citric acid and black cherry flavor. 
     
     
         12 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is present in the rapidly infusing composition in an amount of 5 to 70 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         13 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is in the form of a micronized solid having a D90 diameter of 10 to 80 μm. 
     
     
         14 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is selected from the group consisting of sildenafil, tadalafil, avanafil, vardenafil, lodenafil, mirodenafil, and udenafil, or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is sildenafil or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is sildenafil citrate. 
     
     
         17 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is tadalafil or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is avanafil or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is vardenafil or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The rapidly infusing composition of  claim 1 , wherein the rapidly infusing composition further comprises a sweetener, a colorant, or both. 
     
     
         21 . The rapidly infusing composition of  claim 20 , wherein the rapidly infusing composition comprises the sweetener, and the sweetener comprises a mixture of sucralose and acesulfame-K. 
     
     
         22 . The rapidly infusing composition of  claim 20 , wherein the rapidly infusing composition comprises the colorant, and the colorant comprises FD&C Blue #2. 
     
     
         23 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is not coated or encapsulated. 
     
     
         24 . The rapidly infusing composition of  claim 1 , wherein the PDE 5  inhibitor is not complexed with an ion exchange resin. 
     
     
         25 . The rapidly infusing composition of  claim 1 , which is free of alkaline buffering agents. 
     
     
         26 . A process for manufacturing the rapidly infusing composition of  claim 1 , comprising:
 dissolving gelatin and sugar alcohol in water to form a solution;   adding the PDE 5  inhibitor to the solution, followed by the flavorant, to form a drug product suspension; and   lyophilizing the drug product suspension to remove water and form the rapidly infusing composition.   
     
     
         27 . A method of treating a condition in a subject that is responsive to inhibition of PDE 5 , the method comprising administering to the subject in need thereof, via the oral mucosa, a therapeutically effective amount of the rapidly infusing composition of  claim 1 . 
     
     
         28 . The method of  claim 27 , wherein the rapidly infusing composition is administered buccally to the subject via the buccal mucosa. 
     
     
         29 . The method of  claim 27 , wherein the therapeutically effective amount of the rapidly infusing composition is that which provides from 1 to 200 mg of the PDE 5  inhibitor per dose. 
     
     
         30 . The method of  claim 27 , wherein the rapidly infusing composition is administered to the subject once per day as needed (p.r.n). 
     
     
         31 . The method of  claim 27 , wherein the rapidly infusing composition is administered to the subject once a day (q.d.). 
     
     
         32 . The method of  claim 27 , wherein the subject is a human. 
     
     
         33 . A method of treating erectile dysfunction in a subject, the method comprising administering to the subject in need thereof, via the oral mucosa, a therapeutically effective amount of the rapidly infusing composition of  claim 1 . 
     
     
         34 . The method of  claim 33 , wherein the rapidly infusing composition is administered buccally to the subject via the buccal mucosa. 
     
     
         35 . The method of  claim 33 , wherein the therapeutically effective amount of the rapidly infusing composition is that which provides from 1 to 200 mg of the PDE 5  inhibitor per dose. 
     
     
         36 . The method of  claim 33 , wherein the rapidly infusing composition is administered to the subject once per day as needed (p.r.n). 
     
     
         37 . The method of  claim 33 , wherein the rapidly infusing composition is administered to the subject once a day (q.d.). 
     
     
         38 . The method of  claim 33 , wherein the subject is a human male.