Non-hygroscopic salts of 5-ht2c agonists

Abstract

Salts of the 5-HT2C-receptor agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, and dosage forms comprising them that are useful for, inter alia, weight management.

1 . A salt selected from:
 (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-edisylate salt;   (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine phosphate salt;   (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine citrate salt;   (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-oxalate salt;   (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine succinate salt; and   (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine oxoglutarate salt; and   
       pharmaceutically acceptable salts, solvates and hydrates thereof. 
     
     
         2 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-edisylate salt. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine phosphate salt. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine citrate salt hemihydrate. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-oxalate salt. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine succinate salt. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine oxoglutarate salt. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . The salt according to  claim 1 , that is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine oxoglutarate salt solvate. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . A pharmaceutical composition comprising a salt according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         24 . A process for preparing a pharmaceutical composition comprising admixing a salt according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         25 . A dosage form comprising a therapeutically effective amount of a salt selected from: a pharmaceutically acceptable salt of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and pharmaceutically acceptable solvates and hydrates thereof, wherein said dosage form is a non-hygroscopic dosage form. 
     
     
         26 . The dosage form according to  claim 25 , wherein said salt absorbs:
 less than about 2% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 1% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 0.6% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 0.5% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 0.4% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 0.3% water by weight after about 2 h at about 90% RH and about 25° C.;   less than about 0.2% water by weight after about 2 h at about 90% RH and about 25° C.; or   less than about 0.1% water by weight after about 2 h at about 90% RH and about 25° C.   
     
     
         27 . A dosage form comprising a therapeutically effective amount of a salt according to  claim 1 . 
     
     
         28 . A method for weight management, comprising administering to an individual in need thereof, a therapeutically effective amount of a salt according to  claim 1 . 
     
     
         29 . The method according to  claim 28 , wherein said weight management comprises one or more of: weight loss, maintenance of weight loss, decreased food consumption, increasing meal-related satiety, reducing pre-meal hunger, and reducing intra-meal food intake. 
     
     
         30 . (canceled) 
     
     
         31 . The method according to  claim 28 , wherein said individual in need of weight management is selected from:
 an obese patient with an initial body mass index ≧30 kg/m 2 ;   an overweight patient with an initial body mass index ≧27 kg/m 2  in the presence of at least one weight related comorbid condition; and   an overweight patient with an initial body mass index ≧27 kg/m 2  in the presence of at least one weight related comorbid condition; wherein said weight related co-morbid condition is selected from: hypertension, dyslipidemia, cardiovascular disease, glucose intolerance, and sleep apnea.   
     
     
         32 . The method according to  claim 28 , further comprising administering a second anti-obesity agent to said individual. 
     
     
         33 . The method according to  claim 32 , wherein said second anti-obesity agent is selected from: chlorphentermine, clortermine, phenpentermine, and phentermine, and pharmaceutically acceptable salts, solvates, and hydrates thereof. 
     
     
         34 . The method according to  claim 28 , further comprising administering an anti-diabetes agent to said individual. 
     
     
         35 . The method according to  claim 34 , wherein said anti-diabetes agent is metformin. 
     
     
         36 .- 50 . (canceled)