Compositions and methods for treating schizophrenia

Abstract

The disclosure provides a novel polymorph of Compound (I):2-((1-(2-(4-Fluorophenyl)-2-oxoethyl)piperidin-4-yl)methyl)isoindolin-1-one monohydrochloride dihydrate, i.e., Form (A) of Compound (I).HCl.2H2O. Pharmaceutical compositions comprising Form (A) of Compound (I).HCl.2H2O and related methods of treatment are also disclosed.

1 . A crystalline form of Compound (I); 
       
         
           
           
               
               
           
         
         comprising a polymorph form (A) of Compound (I).HCl.2H 2 O, and wherein the form (A) has a X-ray powder diffraction pattern with at least one major peak substantially similar to at least one major peak shown in  FIG. 11 . 
       
     
     
         2 . The crystalline form of  claim 1 , wherein the form (A) has X-ray powder diffraction pattern peaks at approximately 7.6 and 14.3° 2θ using Cu Kα radiation. 
     
     
         3 .- 8 . (canceled) 
     
     
         9 . A pharmaceutical formulation comprising Compound (I); 
       
         
           
           
               
               
           
         
         wherein the formulation comprises a release modifier that provides a maximum plasma concentration (C max ) of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O below 50 ng/mL when a dose of between about 1-100 mg of the formulation is administered to a human. 
       
     
     
         10 . The pharmaceutical formulation of  claim 9 , when Compound (I) is present as the polymorph form (A) of Compound (I).HCl.2H 2 O. 
     
     
         11 . The pharmaceutical formulation of  claim 10 , comprising about 10-75 mg of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O. 
     
     
         12 . The pharmaceutical formulation of  claim 10 , comprising about 15-65 mg of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O. 
     
     
         13 . The pharmaceutical formulation of  claim 10 , comprising about 16 mg, about 32 mg, about 40 mg, or about 64 mg of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O. 
     
     
         14 . The pharmaceutical formulation of  claim 10 , wherein the release modifier is a hypromellose. 
     
     
         15 .- 27 . (canceled) 
     
     
         28 . A method of treating a neuropsychiatric disease or disorder, comprising administering a therapeutically effective amount of the pharmaceutical formulation of  claim 9  to a subject in need thereof. 
     
     
         29 . The method of  claim 28 , wherein the neuropsychiatric disease or disorder is schizophrenia. 
     
     
         30 .- 37 . (canceled) 
     
     
         38 . A method of treating a sleep disorder, comprising administering a therapeutically effective amount of the pharmaceutical formulation of  claim 9  to a subject in need thereof. 
     
     
         39 . The method of  claim 38 , wherein at least one aspect of a sleep disorder is treated or diminished. 
     
     
         40 . The method of  claim 39  wherein the at least one aspect of a sleep disorder is selected from sleep period time, one or more segments of sleep period time, overall sleep continuity, and sleep architecture. 
     
     
         41 . The method of  claim 38 , wherein the sleep disorder is associated with schizophrenia. 
     
     
         42 . A kit comprising the pharmaceutical formulation of  claim 9 , and instructions for use.