Solid pharmaceutical composition containing 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta (c)chromen-3-yl sulfamate and polymorphs thereof

Abstract

The present invention relates to a solid pharmaceutical composition including the active principle 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate. The present invention also relates to polymorphs of the 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate compound.

1 . A solid pharmaceutical composition comprising a 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate as an active ingredient and at least one pharmaceutically acceptable carrier. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the solid composition is a capsule. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the solid composition is a tablet. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the tablet comprises by total weight of the composition 1 to 30% active ingredient, from 40 to 92% thinner, 0.1 to 20% disintegrant, 0.1 to 8% binder, 0.1 to 3% slip agent, and 0.5 to 3% of lubricant, and about 4.8% coating solution in relation to the total weight of the tablet. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , further comprising a diluent of mannitol, lactose or lactose monohydrate, starch, calcium carbonate, microcrystalline cellulose or maltodextrin. 
     
     
         6 . The pharmaceutical composition according to  claim 4 , wherein the disintegrant is starch, croscarmellose sodium, sodium starch glycolate or crospovidone. 
     
     
         7 . The pharmaceutical composition according to  claim 4 , wherein the binder is polyvinyl pyrrolidone, copolymers of N-vinyl-2-pyrrolidone and vinyl acetate, carboxymethylcellulose, pregelatinized starch or methylcellulose. 
     
     
         8 . The pharmaceutical composition according to  claim 4 , wherein the lubricant is magnesium stearate, sodium stearyl fumarate, calcium stearate or hydrogenated vegetable oil. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , comprising either:
 (a) microcrystalline cellulose and/or copolymers of N-vinyl-2-pyrrolidone and vinyl acetate; or   (b) microcrystalline cellulose and/or carboxymethylcellulose.   
     
     
         10 . The pharmaceutical composition according to  claim 3 , wherein the tablet comprises by total weight of the composition 8 to 20% active ingredient, 20 to 40% lactose, 25 to 50% of microcrystalline cellulose 2 to 8% copolymers of N-vinyl-2-pyrrolidone and vinyl acetate 1 to 5% of sodium starch glycolate, 0.2 to 1.4% flow agent, and 0.5 to 2% of lubricant on the total weight of the tablet. 
     
     
         11 . (canceled) 
     
     
         12 . The pharmaceutical composition according to  claim 1 , wherein the 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate is a particle size between 1 and 15 μm. 
     
     
         13 . The pharmaceutical composition according to claim, wherein the active ingredient is immediately released. 
     
     
         14 . The pharmaceutical composition according to  claim 3 , wherein the tablet does not exceed 800 mg. 
     
     
         15 . A method for preparing a solid pharmaceutical composition comprising the 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate according to  claim 1 , comprising a step of reducing the particle size of the active ingredient. 
     
     
         16 . The method of  claim 15 , comprising reducing the particle size by micronization. 
     
     
         17 . A method for preparing the solid pharmaceutical composition according to  claim 1  comprising the steps of:
 (a) screening the components; 
 (b) wet granulating, mixing, and compressing the components; and 
 (c) preparing and applying a coating solution, wherein said coating solution may include a substance that improves fluidity. 
 
     
     
         18 . The method according to  claim 17 , wherein the substance that improves fluidity is a slip agent. 
     
     
         19 . The method according to  claim 17 , wherein during the wet granulating step, the mass of water relative to the total mass of the active ingredient to the premixed binder, diluent and disintegrant, is between about 10 and 30%. 
     
     
         20 . The method according to  claim 17 , wherein after the wet granulating step, the granules are dried to a residual moisture of less than 3%. 
     
     
         21 - 35 . (canceled) 
     
     
         36 . The pharmaceutical composition according to  claim 14 , wherein the tablet does not exceed 400 mg. 
     
     
         37 . The method according to  claim 18 , wherein the substance the slip agent is a colloidal solution of silicon dioxide.