Epinephrine fine particles and methods for use thereof for treatment of conditions responsive to epinephrine

Abstract

The invention provides compositions including epinephrine fine particles, including epinephrine nanoparticles or nanocrystals and epinephrine microparticles or microcrystals, and methods for therapeutic use of the compositions for the treatment of conditions responsive to epinephrine such as a cardiac event or an allergic reaction, particularly anaphylaxis. The epinephrine fine particles can be incorporated into orally-disintegrating and fast-disintegrating tablet pharmaceutical formulations and can significantly increase the sublingual bioavailability of epinephrine, and thereby reduce the epinephrine dose required.

1 . A pharmaceutical composition comprising epinephrine nanocrystals or microcrystals, the composition formulated for buccal or sublingual administration. 
     
     
         2 . The pharmaceutical composition in accordance with  claim 1 , further comprising at least one of a pharmaceutically-acceptable carrier, a surfactant, a penetration enhancer, and a mucoadhesive. 
     
     
         3 . (canceled) 
     
     
         4 . The pharmaceutical composition in accordance with  claim 1 , wherein the composition includes a pharmaceutically-effective dose of approximately 10 mg to approximately 40 mg epinephrine nanocrystals or microcrystals. 
     
     
         5 . The pharmaceutical composition in accordance with  claim 1 , wherein the composition includes a pharmaceutically-effective dose of approximately 10 mg epinephrine nanocrystals or microcrystals. 
     
     
         6 . The pharmaceutical composition in accordance with  claim 2 , further comprising at least one of a taste enhancer and a sweetening agent and mouthfeel enhancer. 
     
     
         7 . The pharmaceutical composition in accordance with  claim 6 , further comprising at least one of a filler, a lubricant, and a disintegrant. 
     
     
         8 . The pharmaceutical composition in accordance with  claim 6 , wherein the taste enhancer is citric acid and the sweetening agent and mouthfeel enhancer is mannitol. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . A method for treating a condition responsive to epinephrine in a subject in need thereof, comprising:
 providing a composition including epinephrine nanocrystals or microcrystals and at least one pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         13 . The method in accordance with  claim 12 , wherein the composition includes a pharmaceutically-effective dose of approximately 10 mg to approximately 40 mg epinephrine nanocrystals or microcrystals. 
     
     
         14 . The method in accordance with  claim 12 , wherein the composition includes a pharmaceutically-effective dose of approximately 10 mg epinephrine nanocrystals or microcrystals. 
     
     
         15 . The method in accordance with  claim 12 , wherein the condition is a cardiac event or an allergic reaction. 
     
     
         16 . The method in accordance with  claim 15 , wherein the cardiac event is cardiac arrest and the allergic reaction is anaphylaxis, asthma, or bronchial asthma. 
     
     
         17 - 38 . (canceled) 
     
     
         39 . The method in accordance with  claim 12 , wherein the condition is a breathing difficulty. 
     
     
         40 . The method in accordance with  claim 39 , wherein the breathing difficulty is associated with anaphylaxis, asthma, bronchial asthma, bronchitis, emphysema, or respiratory infections. 
     
     
         41 . The method in accordance with  claim 12 , wherein the treating includes enhancing sublingual bioavailability of epinephrine. 
     
     
         42 . The pharmaceutical composition in accordance with  claim 1 , wherein the epinephrine is an epinephrine base or an epinephrine bitartrate salt. 
     
     
         43 . The pharmaceutical composition in accordance with  claim 1 , wherein the composition is an oral disintegrating tablet (ODT) capable of fully dissolving or disintegrating in less than about one minute. 
     
     
         44 . The pharmaceutical composition in accordance with  claim 1 , wherein the composition is encapsulated within a polymer. 
     
     
         45 . A pharmaceutical composition comprising epinephrine fine particles, the composition formulated for buccal or sublingual administration. 
     
     
         46 . The pharmaceutical composition in accordance with  claim 45 ,
 wherein the epinephrine fine particles range in size from about 2.5 μm or less to about 100 nm.