Novel olanzapine forms and related methods of treatment

Abstract

The invention provides novel soluble olanzapine forms. These forms include salts, co-crystals, and solvates of olanzapine. The invention also provides novel pharmaceutical compositions comprising these novel soluble forms and related methods of treatment. Compositions and methods of the invention of the invention are useful in the treatment of psychosis and functional bowel disorders.

1 - 44 . (canceled)  
     
     
         45 . An olanzapine salt comprising olanzapine fumarate.  
     
     
         46 . The olanzapine salt of  claim 45 , wherein the salt is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms, of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 9.49, 13.99, and 15.83 degrees;    (ii) 12.71, 17.13, and 19.67 degrees;    (iii) 21.43, 22.29, and 22.99 degrees;    (iv) 9.49 degrees;    (v) 9.49 and 13.99 degrees; and    (vi) 15.83 and 22.29 degrees.    
     
     
         47 . The olanzapine salt of  claim 45 , wherein said salt is crystalline.  
     
     
         48 . The olanzapine salt of  claim 45 , wherein said salt exhibits a powder X-ray diffraction pattern substantially as shown in  FIG. 1 .  
     
     
         49 . A pharmaceutical composition comprising the olanzapine salt of  claim 45 .  
     
     
         50 . An olanzapine salt comprising olanzapine maleate.  
     
     
         51 . The olanzapine salt of  claim 50 , wherein the salt is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 5.57, 12.95, and 16.79 degrees;    (ii) 11.97, 19.25, and 21.11 degrees;    (iii) 5.57, 19.25, and 22.23 degrees;    (iv) 5.57 degrees;    (v) 5.57 and 12.95 degrees; and    (vi) 16.79 and 19.25 degrees.    
     
     
         52 . The olanzapine salt of  claim 50 , wherein said salt is crystalline.  
     
     
         53 . The olanzapine salt of  claim 50 , wherein said salt exhibits a powder X-ray diffraction pattern substantially as shown in  FIG. 3 .  
     
     
         54 . A pharmaceutical composition comprising the olanzapine salt of  claim 50 .  
     
     
         55 . An olanzapine salt comprising olanzapine malonate.  
     
     
         56 . The olanzapine salt of  claim 55 , wherein the salt is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 7.37, 9.45, and 12.41 degrees;    (ii) 14.83, 20.51, and 21.35 degrees;    (iii) 7.37, 17.71, and 23.19 degrees;    (iv) 7.37 degrees;    (v) 9.45 and 12.95 degrees; and    (vi) 9.85 and 17.71 degrees.    
     
     
         57 . The olanzapine salt of  claim 55 , wherein said salt is crystalline.  
     
     
         58 . The olanzapine salt of  claim 55 , wherein said salt exhibits a powder X-ray diffraction pattern substantially as shown in  FIG. 5 .  
     
     
         59 . A pharmaceutical composition comprising the olanzapine salt of  claim 55 .  
     
     
         60 . An olanzapine solvate comprising methanol.  
     
     
         61 . The olanzapine solvate of  claim 60 , wherein the solvate is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 8.61, 16.45, and 18.85 degrees;    (ii) 16.45, 19.97, and 23.09 degrees;    (iii) 20.85, 22.05, and 24.73 degrees;    (iv) 8.61 degrees;    (v) 8.61 and 16.45 degrees; and    (vi) 18.85 and 19.97 degrees.    
     
     
         62 . The olanzapine solvate of  claim 60 , wherein the solvate exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: a=10.1416(8) angstroms, b=12.2793(9) angstroms, c=14.1147(11) angstroms, beta=91.7860(10) degrees.  
     
     
         63 . The olanzapine solvate of  claim 60 , wherein said solvate is crystalline.  
     
     
         64 . The olanzapine solvate of  claim 60 , wherein said solvate exhibits a powder X-ray diffraction pattern substantially as shown in  FIG. 6 .  
     
     
         65 . A pharmaceutical composition comprising the olanzapine solvate of  claim 60 .  
     
     
         66 . An olanzapine co-crystal comprising olanzapine and nicotinamide.  
     
     
         67 . The olanzapine co-crystal of  claim 66 , wherein said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 4.89, 8.65, and 17.17 degrees;    (ii) 23.97, 24.61, and 25.57 degrees;    (iii) 4.89, 17.17, and 25.57 degrees;    (iv) 4.89 degrees;    (v) 4.89 and 8.65 degrees; and    (vi) 17.17 and 23.97 degrees.    
     
     
         68 . The olanzapine co-crystal of  claim 66 , wherein said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 8.65, 11.87, and 14.53 degrees;    (ii) 17.53, 18.09, and 23.89 degrees;    (iii) 8.65, 17.53, and 24.19 degrees;    (iv) 8.65 degrees;    (v) 11.87 and 14.53 degrees; and    (vi) 18.09 and 23.89 degrees.    
     
     
         69 . The olanzapine co-crystal of  claim 66 , wherein said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 6.43, 12.85, and 18.69 degrees;    (ii) 9.55, 14.91, and 21.85 degrees;    (iii) 6.43, 14.91, and 19.83 degrees;    (iv) 6.43 degrees;    (v) 12.85 and 18.69 degrees; and    (vi) 6.43 and 21.85 degrees.    
     
     
         70 . The olanzapine co-crystal of  claim 66 , wherein said co-crystal exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: a=14.0961(12) angstroms, b=12.5984(10) angstroms, c=27.219(2) angstroms, beta=97.396(2) degrees.  
     
     
         71 . The olanzapine co-crystal of  claim 66 , wherein said co-crystal exhibits a powder X-ray diffraction pattern substantially as shown in a figure selected from the group consisting of  FIG. 14B ,  FIG. 16 , and  FIG. 17B .  
     
     
         72 . A pharmaceutical composition comprising the olanzapine co-crystal of  claim 66 .  
     
     
         73 . An olanzapine solvate comprising propylene glycol.  
     
     
         74 . The olanzapine solvate of  claim 73 , wherein said solvate is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein said X-ray diffraction pattern comprises peaks selected from the group consisting of: 
 (i) 8.39, 11.71, and 15.55 degrees;    (ii) 13.95, 15.55, and 19.55 degrees;    (iii) 14.45, 17.91, and 21.47 degrees;    (iv) 8.39 degrees;    (v) 8.39 and 21.47 degrees; and    (vi) 11.71 and 15.55 degrees.    
     
     
         75 . The olanzapine solvate of  claim 73 , wherein said solvate exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: a=10.4264(9) angstroms, b=13.3916(11) angstroms, c=14.4424(12) angstroms, beta=95.503(2) degrees.  
     
     
         76 . The olanzapine solvate of  claim 73 , wherein said solvate is crystalline.  
     
     
         77 . The olanzapine solvate of  claim 73 , wherein said solvate exhibits a powder X-ray diffraction pattern substantially as shown in  FIG. 10B .  
     
     
         78 . A pharmaceutical composition comprising the olanzapine solvate of  claim 73 .  
     
     
         79 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 49  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.  
     
     
         80 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 54  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.  
     
     
         81 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 59  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.  
     
     
         82 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 65  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.  
     
     
         83 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 72  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.  
     
     
         84 . A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical composition of  claim 78  to a patient suffering from psychosis, a functional bowel disorder, or irritable bowel syndrome.