Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereof

Abstract

This invention relates to a highly thermally stable novel anhydrous crystalline polymorphic form of venlafaxine hydrochloride, methods for the preparation thereof, and its use.

1 . A method of treating depression in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       2 . A method of treating generalized anxiety disorder in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       3 . A method of treating social anxiety disorder in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       4 . A method of treating post traumatic stress disorder in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       5 . A method of treating panic disorder in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       6 . A method of preventing relapse or recurrence of depression disorder in a mammal in need thereof comprising administering to the mammal an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       7 . A method of treating depression, generalized anxiety disorder, social anxiety disorder, post traumatic stress disorder or panic disorder, or preventing the relapse or recurrence of depression, comprising administering to a mammal in need thereof an effective amount of a crystalline polymorph of venlafaxine hydrochloride exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 11.31, 14.01, 14.54, 14.85, 15.48, 15.81, 16.17, 16.94, 17.68, 18.02, 18.48, 19.29, 19.69, 20.46, 20.74, 21.86, 22.33, 22.67, 22.95, 23.17, 24.06, 24.61, 25.13, 26.62, 26.97, 27.64, 28.25, 29.01, 29.96, 31.01, 31.61, 32.75, 34.54, 35.50, 35.95 and 36.91.  
   
   
       8 . A method of treating depression, generalized anxiety disorder, social anxiety disorder, post traumatic stress disorder or panic disorder, or preventing the relapse or recurrence of depression, comprising administering to a mammal in need thereof an effective amount of a crystalline polymorph of venlafaxine hydrochloride having an X-ray powder diffraction pattern substantially the same as that shown in  FIG. 1 .  
   
   
       9 . A method of treating depression, generalized anxiety disorder, social anxiety disorder, post traumatic stress disorder or panic disorder, or preventing the relapse or recurrence of depression, comprising administering to a mammal in need thereof an effective amount of substantially pure anhydrous venlafaxine hydrochloride.  
   
   
       10 . The method of  claim 9  wherein the anhydrous venlafaxine hydrochloride has a melting point of about 219° C.  
   
   
       11 . Substantially pure anhydrous venlafaxine hydrochloride.  
   
   
       12 . A method of preparing anhydrous venlafaxine hydrochloride, the method comprising heating form I or II of venlafaxine hydrochloride or a mixture thereof to at least about 197° C. for a time sufficient to form the anhydrous venlafaxine hydrochloride.  
   
   
       13 . The method of  claim 12 , wherein the venlafaxine hydrochloride is heated to at least about 200° C.  
   
   
       14 . The method of  claim 12 , wherein the venlafaxine hydrochloride is heated for at least about 60 minutes.  
   
   
       15 . The method of  claim 13 , wherein the venlafaxine hydrochloride is heated for at least 150 minutes.  
   
   
       16 . The method of  claim 12  wherein the anhydrous venlafaxine hydrochloride exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       17 . The method of  claim 12  wherein the anhydrous venlafaxine hydrochloride exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 11.31, 14.01, 14.54, 14.85, 15.48, 15.81, 16.17, 16.94, 17.68, 18.02, 18.48, 19.29, 19.69, 20.46, 20.74, 21.86, 22.33, 22.67, 22.95, 23.17, 24.06, 24.61, 25.13, 26.62, 26.97, 27.64, 28.25, 29.01, 29.96, 31.01, 31.61, 32.75, 34.54, 35.50, 35.95 and 36.91.  
   
   
       18 . The method of  claim 12  wherein the anhydrous venlafaxine hydrochloride exhibits an X-ray powder diffraction pattern substantially as that shown in  FIG. 1 .  
   
   
       19 . The method of  claim 12  wherein the anhydrous venlafaxine is substantially pure.  
   
   
       20 . Anhydrous venlafaxine hydrochloride prepared according to  claim 12 .  
   
   
       21 . Anhydrous venlafaxine hydrochloride prepared according to  claim 20  which is substantially pure.  
   
   
       22 . Anhydrous venlafaxine hydrochloride prepared according to  claim 12  having a melting point of 219.  
   
   
       23 . Anhydrous venlafaxine hydrochloride prepared according to  claim 22  which is substantially pure.  
   
   
       24 . Anhydrous venlafaxine hydrochloride prepared according to  claim 12  exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74.  
   
   
       25 . Anhydrous venlafaxine hydrochloride prepared according to  claim 24  which is substantially pure.  
   
   
       26 . Anhydrous venlafaxine hydrochloride prepared according to  claim 12  exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at about 5.67, 7.28, 9.14, 9.67, 10.77, 11.31, 14.01, 14.54, 14.85, 15.48, 15.81, 16.17, 16.94, 17.68, 18.02, 18.48, 19.29, 19.69, 20.46, 20.74, 21.86, 22.33, 22.67, 22.95, 23.17, 24.06, 24.61, 25.13, 26.62, 26.97, 27.64, 28.25, 29.01, 29.96, 31.01, 31.61, 32.75, 34.54, 35.50, 35.95 and 36.91.  
   
   
       27 . Anhydrous venlafaxine hydrochloride prepared according to  claim 26  which is substantially pure.  
   
   
       28 . Anhydrous venlafaxine hydrochloride prepared according to  claim 12  exhibiting an X-ray powder diffraction pattern substantially as that shown in  FIG. 1 .  
   
   
       29 . Substantially pure anhydrous venlafaxine hydrochloride prepared according to  claim 12  exhibiting an X-ray powder diffraction pattern substantially as that shown in  FIG. 1 .  
   
   
       30 . A method of preparing a crystalline polymorph of venlafaxine hydrochloride in substantially pure form, the method comprising: 
 (a) obtaining venlafaxine hydrochloride having an X-ray powder diffraction pattern substantially the same as that shown in  FIG. 1  in substantially pure form; and    (b) converting the venlafaxine hydrochloride of step (a) into a different crystalline polymorphic form.    
   
   
       31 . The method of  claim 30 , wherein the venlafaxine hydrochloride formed in step (b) is Form I of venlafaxine hydrochloride.  
   
   
       32 . The method of  claim 30  wherein the venlafaxine hydrochloride formed in step (b) is Form II of venlafaxine hydrochloride.