Epinephrine nanoparticles, methods of fabrication thereof, and methods for use thereof for treatment of conditions responsive to epinephrine

Abstract

The invention provides compositions including epinephrine nanoparticles and methods for therapeutic use of the compositions in the treatment of conditions responsive to epinephrine such as a cardiac event or an allergic reaction, particularly anaphylaxis. The epinephrine nanoparticles 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. Additionally, the invention provides methods for fabrication of stabilized epinephrine nanoparticles for use in the described compositions.

1 . A pharmaceutical composition comprising epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TPP), the composition formulated for buccal or sublingual administration. 
     
     
         2 . The pharmaceutical composition in accordance with  claim 1 , wherein the epinephrine is epinephrine bitartrate. 
     
     
         3 . (canceled) 
     
     
         4 . The pharmaceutical composition in accordance with  claim 1 , further comprising at least one of a pharmaceutically-acceptable carrier, a penetration enhancer, and a mucoadhesive. 
     
     
         5 . The pharmaceutical composition in accordance with  claim 4 , furthermore comprising at least one of a taste enhancer and a sweetening agent and mouthfeel enhancer. 
     
     
         6 . The pharmaceutical composition in accordance with  claim 5 , wherein the taste enhancer is citric acid and the sweetening agent and mouthfeel enhancer is mannitol. 
     
     
         7 - 15 . (canceled) 
     
     
         16 . A method for fabricating epinephrine nanoparticles comprising:
 a) preparing a solution including chitosan, acetic acid, and water;   b) preparing a solution including tripolyphosphate (TPP) and epinephrine; and   c) adding the solution of step b) to the solution of step a) and mixing together.   
     
     
         17 . The method in accordance with  claim 16 , further comprising a step of adding at least one of a taste enhancer and a sweetening agent and mouthfeel enhancer. 
     
     
         18 . The method in accordance with  claim 17 , wherein the taste enhancer is citric acid and the sweetening agent and mouthfeel enhancer is mannitol. 
     
     
         19 . The method in accordance with  claim 16 , wherein the epinephrine is epinephrine bitartrate. 
     
     
         20 . An epinephrine nanoparticle produced in accordance with the method of  claim 16 . 
     
     
         21 . A method for enhancing sublingual bioavailability of epinephrine in a subject in need thereof, comprising:
 providing a composition including epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TPP) and a pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         22 . A method for treating a condition responsive to epinephrine in a subject in need thereof, comprising:
 providing a composition including epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TPP) and a pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         23 . The method in accordance with  claim 22 , wherein the condition is a cardiac event or an allergic reaction. 
     
     
         24 . The method in accordance with  claim 23 , wherein the cardiac event is cardiac arrest and the allergic reaction is anaphylaxis, asthma, or bronchial asthma. 
     
     
         25 . A method for treatment of a breathing difficulty in a subject in need thereof, comprising:
 providing a composition including epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TTP) and a pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         26 . The method in accordance with  claim 25 , wherein the breathing difficulty is associated with anaphylaxis, asthma, bronchial asthma, bronchitis, emphysema, or respiratory infections. 
     
     
         27 . A method for treatment of an allergic emergency in a subject diagnosed with or suspected of having an allergic emergency, comprising:
 providing a composition including epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TPP) and a pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         28 . The method in accordance with  claim 27 , wherein the allergic emergency is anaphylaxis, asthma, or bronchial asthma. 
     
     
         29 . A method for treatment of a cardiac event in a subject diagnosed with or suspected of having a cardiac event, comprising:
 providing a composition including epinephrine nanoparticles encapsulated with chitosan and tripolyphosphate (TPP) and a pharmaceutically-acceptable carrier; and   administering the composition to the subject.   
     
     
         30 . The method in accordance with  claim 29 , wherein the cardiac event is cardiac arrest. 
     
     
         31 - 41 . (canceled)