Crystalline forms of hydroxynorketamine

Abstract

The present invention provides novel, stable, processable and pharmaceutically acceptable salt forms of 2R,6R-hydrox-ynorketamineor 2S,6S-hydroxynorketamine with high aqueous solubility.

1 - 37 . (canceled) 
     
     
         38 . An acid addition salt of 2R,6R-hydroxynorketamine or 2S,6S-hydroxynorketamine wherein the acid comprises either (i) one or more carboxylic acid groups and an amide group or (ii) two or more carboxylic acid groups, with the proviso that the acid addition salt is not 2R,6R-hydroxynorketamine L-tartrate or 2S,6S-hydroxynorketamine D-tartrate. 
     
     
         39 . The acid addition salt of  claim 38  wherein the acid has Formula I or II 
       
         
           
           
               
               
           
         
       
       wherein
 n=0-3, 
 R 1  and R 2  are each independently selected from —H, —OH, and —COOH, and wherein when n=2, both R 2  may together represent a C═C bond, and wherein 
 R 3  is ═O or —COOH. 
 
     
     
         40 . An acid addition salt of  claim 38  wherein the acid has Formula III, IV or V: 
       
         
           
           
               
               
           
         
       
       wherein
 n=0-3, 
 R 1  and R 2  are each independently selected from —H, —OH, and —COOH, 
 wherein when n=2 or 3, two adjacent R 2  groups may together represent a C═C bond, and wherein 
 R 3  is ═O, or —COOH. 
 
     
     
         41 . The acid addition salt of  claim 39  wherein the acid has Formula I, wherein n=1 or 2, and wherein each R 1  is —H and one or both R 2  is —OH and any other R 2  is —H. 
     
     
         42 . The acid addition salt of  claim 39  wherein the acid has Formula I, wherein n=2, and wherein each R 1  is H and both R 2  are taken together to represent a C═C bond. 
     
     
         43 . The acid addition salt of  claim 39  wherein the acid has Formula II, wherein n=1 or 2, and wherein R 3  is ═O. 
     
     
         44 . The acid addition salt of  claim 38  wherein the acid is aspartic acid, citric acid, fumaric acid, glutaric acid, glutamic acid, hippuric acid, malic acid, maleic acid, mucic acid, oxalic acid, pyroglutamic acid, or succinic acid. 
     
     
         45 . The acid addition salt of  claim 38  selected from 2R,6R-hydroxynorketamine difumarate, 2S,6S-hydroxynorketamine difumarate, 2R,6R-hydroxynorketamine D-pyroglutamate, 2S,6S-hydroxynorketamine D-pyroglutamate, 2R,6R-hydroxynorketamine L-pyroglutamate, 2S,6S-hydroxynorketamine L-pyroglutamate, 2R,6R-hydroxynorketamine L-malate, or 2S,6S-hydroxynorketamine D-malate. 
     
     
         46 . The acid addition salt of  claim 38  in crystalline form, wherein the acid addition salt is 2R,6R-hydroxynorketamine L-pyroglutamate. 
     
     
         47 . The acid addition salt of  claim 45  selected from 2R,6R-hydroxynorketamine L-pyroglutamate and 2S,6S-hydroxynorketamine D-pyroglutamate. 
     
     
         48 . The acid addition salt of  claim 38  selected from 2R,6R-hydroxynorketamine L-tartrate and 2S,6S-hydroxynorketamine D-tartrate, wherein
 (i) the acid addition salt is anhydrous; or 
 (ii) the acid addition salt is hydrated. 
 
     
     
         49 . The acid addition salt of  claim 38  selected from 2R,6R-hydroxynorketamine difumarate and 2S,6S-hydroxynorketamine difumarate. 
     
     
         50 . A solid oral dosage form comprising an acid addition salt according to  claim 38 , wherein the acid addition salt is 2R,6R-hydroxynorketamine L-pyroglutamate. 
     
     
         51 . The solid oral dosage form of  claim 50  comprising a blend of one or more diluent, wherein when the dosage form is a tablet the blend of one or more diluent comprises microcrystalline cellulose, and wherein when the dosage form is a capsule the capsule shell comprises a constituent selected from gelatin and hydroxypropyl methylcellulose.