Details for Patent: 8,697,686

Title:	Crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-thtrahydro-1H-3-benzazepine hydrochloride
Abstract:	The present invention is directed to crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, compositions containing the same and uses thereof.
Inventor(s):	Agarwal; Rajesh K. (San Diego, CA), Betts, III; William L. (San Diego, CA), Henshilwood; James A. (Carlsbad, CA), Kiang; Yuan-Hon (Newbury Park, CA), Post; Noah (San Diego, CA)
Assignee:	Arena Pharmaceuticals, Inc. (San Diego, CA)
Filing Date:	Mar 21, 2012
Application Number:	13/425,669
Claims:	1. A method for preparing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate comprising the step of: exposing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride to water to form (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate. 2. A method according to claim 1, wherein said (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride is hygroscopic. 3. (R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate prepared by the method of claim 1. 4. A method of preparing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate comprising mixing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride with a crystallizing solvent containing water, and inducing precipitation of the hemihydrate from the crystallizing solvent. 5. A method according to claim 4, wherein the crystallizing solvent contains an alcohol, water, and a hydrocarbon. 6. A method according to claim 5, wherein the alcohol is methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1-butanol, 2-butanol, i-butyl alcohol, t-butyl alcohol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, or glycerol. 7. A method according to claim 6, wherein the alcohol is 2-propanol. 8. A method according to claim 5, wherein the hydrocarbon is benzene, cyclohexane, pentane, hexane, toluene, cycloheptane, methylcyclohexane, heptane, ethylbenzene, m-xylene, o-xylene, p-xylene, octane, indane, nonane, or naphthalene. 9. A method according to claim 8, wherein the hydrocarbon is cyclohexane. 10. A method according to claim 5, wherein the weight ratio of alcohol to water in the crystallizing solvent is 35:1 to 25:1. 11. A method according to claim 10, wherein the weight ratio of alcohol to water in the crystallizing solvent is 32:1 to 27:1. 12. A method according to claim 11, wherein the weight ratio of alcohol to water in the crystallizing solvent is 30:1 to 28:1. 13. A method according to claim 12, wherein the weight ratio of alcohol to water is about 29:1. 14. A method according to claim 5, wherein the weight ratio of alcohol plus water to hydrocarbon in the crystallizing solvent is 5:1 to 2:1. 15. A method according to claim 14, wherein the weight ratio of alcohol plus water to hydrocarbon in the crystallizing solvent is 3:1 to 2:1. 16. A method according to claim 15, wherein the weight ratio of alcohol plus water to hydrocarbon in the crystallizing solvent is or about 2.5:1. 17. A method according to claim 4, wherein the weight ratio of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride to crystallizing solvent is 1:2 to 1:15. 18. A method according to claim 17, wherein the weight ratio of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride to crystallizing solvent is 1:6 to 1:10. 19. A method according to claim 18, wherein the weight ratio of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride to crystallizing solvent is about 1:8. 20. A method according to claim 4, wherein the mixture containing the crystallizing solvent and (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride is maintained at and/or heated to a temperature of 40 to 80.degree. C. prior to inducing precipitation. 21. A method according to claim 20, wherein the mixture containing the crystallizing solvent and (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride is maintained at and/or heated to a temperature of 50 to 70.degree. C. prior to inducing precipitation. 22. A method according to claim 21, wherein the mixture containing the crystallizing solvent and (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride is maintained at and/or heated to a temperature of about 60.degree. C. 23. A method according to claim 4, wherein (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride is dissolved in the crystallizing solvent prior to inducing precipitation. 24. A method according to claim 23, wherein the dissolution is achieved by heating the mixture to a temperature between 40 and 80.degree. C. 25. A method according to claim 24, wherein the dissolution is achieved by heating the mixture to a temperature of about 60.degree. C. 26. A method according to claim 4, wherein precipitation of the hemihydrate is induced by cooling the mixture containing the crystallizing solvent and (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride. 27. A method according to claim 26, wherein precipitation of the hemihydrate is induced by cooling the mixture to a temperature of -15 to 15.degree. C. 28. A method according to claim 27, wherein precipitation of the hemihydrate is induced by cooling the mixture to a temperature of -5 to 10.degree. C. 29. A method according to claim 28, wherein precipitation of the hemihydrate is induced by cooling the mixture to a temperature of 0 to 5.degree. C. 30. (R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate obtained by a method according to claim 4. 31. A method of preparing a pharmaceutical composition comprising mixing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate with a pharmaceutically acceptable carrier. 32. The method of claim 31, wherein the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate is prepared by a method of claim 1. 33. The method of claim 31, wherein the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate is prepared by a method of claim 4. 34. A method according to claim 31, further comprising forming the pharmaceutical composition into a tablet, a pill, a powder, a lozenge, a sachet, a cachet, an elixir, a suspension, emulsions, a solution, a syrup, soft or hard gelatin capsule, a suppository, a sterile injectable solution, or a sterile packaged powder. 35. A pharmaceutical composition prepared by the method of claim 31. 36. A pharmaceutical composition prepared by the method of claim 34.