Polymorphic forms of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride

Abstract

The invention relates to new crystalline modifications of the hydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine, crystalline modification of the dihydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine and amorphous 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride which are suitable in particular for the preparation of solid medicaments for the treatment or prevention of depressive disorders, anxiety disorders, bipolar disorders, mania, dementia, substance-related disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleeping disorders, psychiatric disorders, cerebral infarct, tension, for the therapy of side-effects in the treatment of hypertension, cerebral disorders, chronic pain, acromegaly, hypogonadism, secondary amenorrhea, premenstrual syndrome and undesired puerperal lactation.

1 . A pharmaceutical composition comprising an amount of (i) a crystalline modification of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride, and, optionally, (ii) amorphous 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride, wherein if said pharmaceutical composition comprises an amount of (ii), then said pharmaceutical composition is substantially free of free-base 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine. 
     
     
         2 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification I (Form I). 
     
     
         3 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification II (Form II). 
     
     
         4 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification Ill (Form III). 
     
     
         5 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification IV (Form IV). 
     
     
         6 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification V (Form V). 
     
     
         7 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification VI (Form VI). 
     
     
         8 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification VII (Form VII). 
     
     
         9 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification VIII (Form VIII). 
     
     
         10 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification IX (Form IX). 
     
     
         11 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification X (Form X). 
     
     
         12 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification XI (Form XI). 
     
     
         13 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification XII (Form XII). 
     
     
         14 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification XIII (Form XIII). 
     
     
         15 . The pharmaceutical composition of  claim 1 , where said crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine comprises crystalline modification XIV (Form XIV). 
     
     
         16 . A method of treating a patient suffering from a major depressive disorder comprising administering to said patient the pharmaceutical composition of  claim 1 .