N-n-dimethyltryptamine (dmt) and dmt analog compositions, methods of making, and methods of use thereof

Abstract

Pharmaceutical compositions including an amorphous N—N-dimethyltryptamine (DMT) or a pharmaceutically acceptable salt or prodrug thereof, and a polymeric carrier are described. These compositions are suitable for buccal or sublingual administration to a patient. Methods of treating disorders, including neurological disorders, by administration of these compositions are described.

1 . A composition comprising a pharmaceutically effective amount of an amorphous N,N-dimethyltryptamine (DMT) incorporated within a polymeric carrier matrix. 
     
     
         2 . The composition of  claim 1 , wherein the DMT is characterized by a powder x-ray diffractogram free of any discernable peaks. 
     
     
         3 . The composition of  claim 1 , wherein the DMT is characterized by a differential scanning calorimetry (DSC) spectrum lacking a sharp melting endotherm of crystalline DMT and/or lacking an indication of phase change. 
     
     
         4 . The composition of  claim 1 , wherein the polymeric carrier matrix is a mucoadhesive polymer. 
     
     
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         6 . The composition of  claim 1 , wherein the pharmaceutical composition is capable of producing a T max  between 10 min to 90 min upon administration. 
     
     
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         26 . A composition, comprising:
 about 0.5% to about 60% by weight of an amorphous N—N-dimethyltryptamine or a pharmaceutically acceptable salt or prodrug thereof;   about 15% to about 80% by weight of a mucoadhesive polymer matrix; and   about 0.1% to about 30% by weight of a permeation enhancer.   
     
     
         27 . The composition of  claim 26 , comprising about 20% to about 35% by weight of the N—N-dimethyltryptamine or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         28 . The composition of  claim 26 , comprising about 50% to about 60% by weight of the mucoadhesive polymer matrix. 
     
     
         29 . The composition of  claim 26 , further comprising about 0.5% to about 20% by weight of a plasticizer. 
     
     
         30 . The composition of  claim 26 , comprising about 0.5% to about 5% by weight of the plasticizer. 
     
     
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         46 . The composition of  claim 1 , wherein the DMT remains in an amorphous state after aging at 25° C. and 60% relative humidity for 6 months. 
     
     
         47 . The composition of  claim 46 , characterized by a powder x-ray diffractogram free of any discernable peaks. 
     
     
         48 . The composition of  claim 46 , characterized by a differential scanning calorimetry (DSC) spectrum for absence of sharp melting endotherm of crystalline DMT and/or indication of phase change (e.g., glass transition temperature). 
     
     
         49 . The composition of  claim 1 , wherein the DMT is capable of remaining in an amorphous state after aging at 40° C. and 75% relative humidity for 6 months. 
     
     
         50 . The composition of  claim 49 , characterized by a powder x-ray diffractogram free of any discernable peaks. 
     
     
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         54 . A method of making a pharmaceutical composition, comprising the steps of:
 combining N—N-dimethyltryptamine or a pharmaceutically acceptable salt or prodrug thereof, and excipients in a solvent; and   removing the solvent to provide a polymeric matrix comprising an amorphous N—N-dimethyltryptamine or a pharmaceutically acceptable salt or prodrug thereof.   
     
     
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         65 . A composition prepared according to the method of  claim 54 . 
     
     
         66 . The composition of  claim 65 , wherein the DMT is capable of remaining in an amorphous state after aging at 25° C. and 60% relative humidity for 6 months. 
     
     
         67 . The composition of  claim 66 , characterized by a powder x-ray diffractogram free of any discernable peaks. 
     
     
         68 . The composition of  claim 66 , characterized by a differential scanning calorimetry (DSC) spectrum for absence of sharp melting endotherm of crystalline DMT and/or indication of phase change. 
     
     
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