Stable Pharmaceutical Compositions Comprising a Pyrimidine - Sulfamide

Abstract

The invention relates to stable pharmaceutical compositions comprising the compound of the below formula, or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof.

1 . A pharmaceutical composition comprising:
 a) a compound of the formula I as drawn below, or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof,   
       
         
           
           
               
               
           
         
         b) a filler, 
         c) a disintegrant, 
         d) a surfactant, and 
         e) a lubricant. 
       
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein
 the filler is selected from one or more of the following: lactose, maize starch, pregelatinized starch, dibasic calcium phosphate dihydrate (CaHPO 4 .2H 2 O), microcrystalline cellulose, maltodextrin and mannitol;   the disintegrant is selected from one or more of the following: croscarmellose sodium, sodium starch glycolate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone, alginic acid, sodium alginate, pregelatinized starch, guar gum, clays and ion exchange resins;   the surfactant is selected from the following: sodium lauryl sulphate, polysorbates, polyethylene polyoxypropylene polymers, polyoxylethylene stearates, dioctyl sodium sulfosuccinate, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene C 1-4 -alkyl ethers, sucrose monoesters and lanolin esters and ethers; and   the lubricant is selected from the following: magnesium, aluminium or calcium stearate, stearic acid, sodium stearyl fumarate, talc, sodium benzoate, glyceryl mono fatty acid, polyethylene glycol, hydrogenated cotton seed oil, castor seed oil and sucrose esters.   
     
     
         3 . A pharmaceutical composition according to  claim 2 , which comprises
 a) a compound of the formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof,   b) one or more excipients selected from the group consisting of lactose, maize starch, pregelatinised starch, calcium hydrogen phosphate and microcrystalline   cellulose,   c) polyvinylpyrrolidone,   d) sodium starch glycolate,   e) a surfactant, and   f) a lubricant.   
     
     
         4 . A pharmaceutical composition according to  claim 3 , which comprises
 a) a compound of the formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof, in a total amount of up to 50% in weight based on the total weight of the pharmaceutical composition,   b) one or more excipients selected from the group consisting of lactose, maize starch, pregelatinised starch, calcium hydrogen phosphate and microcrystalline cellulose, in a total amount of 10 to 95% in weight based on the total weight of the pharmaceutical composition,   c) polyvinylpyrrolidone, in a total amount of up to 20% in weight based on the total weight of the pharmaceutical composition,   d) sodium starch glycolate, in a total amount of up to 30% in weight based on the total weight of the pharmaceutical composition,   e) a surfactant, in a total amount of up to 7% in weight based on the total weight of the pharmaceutical composition, and   f) a lubricant, in a total amount of up to 10% in weight based on the total weight of the pharmaceutical composition.   
     
     
         5 . A pharmaceutical composition according to  claim 3 , which comprises:
 a) a compound of the formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof,   b) lactose or lactose monohydrate,   c) microcrystalline cellulose,   d) polyvinylpyrrolidone,   e) sodium starch glycolate,   f) a surfactant, and   g) a lubricant.   
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the surfactant is a polysorbate. 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the lubricant is magnesium stearate. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , which further contains a glidant. 
     
     
         9 . A pharmaceutical composition according to  claim 8 , which comprises:
 a) a compound of the formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof,   b) one or more of excipients selected from the group consisting of lactose, maize starch, pregelatinized starch, calcium hydrogen phosphate and microcrystalline   cellulose,   c) polyvinylpyrrolidone,   d) sodium starch glycolate,   e) sodium lauryl sulphate,   f) colloidal silicon dioxide, and   g) magnesium stearate.   
     
     
         10 . A pharmaceutical composition according to  claim 8 , which comprises:
 a) a compound of formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof, in a total amount of up to 50% in weight based on the total weight of the pharmaceutical composition,   b) a mixture of at least one or more of a filler in a total amount of 30-85% in weight based on the total weight of the pharmaceutical composition,   c) polyvinylpyrrolidone in a range of a total amount of 2 to 5% in weight based on the total weight of the pharmaceutical composition,   d) sodium starch glycolate in a total amount of up to 5% in weight based on the total weight of the pharmaceutical composition,   e) a surfactant in a total amount of up to 3% in weight based on the total weight of the pharmaceutical composition,   f) a glidant in a total amount of up to 1% in weight based on the total weight of the pharmaceutical composition, and   g) a lubricant in a total amount of up to 3% in weight based on the total weight of the pharmaceutical composition,   h) whereby the total weight percentage of the pharmaceutical composition is 100%.   
     
     
         11 . A pharmaceutical composition according to  claim 1 , which further contains tartaric acid. 
     
     
         12 . A pharmaceutical composition according to  claim 1 , which is in the form of a capsule. 
     
     
         13 . A pharmaceutical composition according to  claim 1 , which is in the form of a tablet. 
     
     
         14 . A pharmaceutical composition according to  claim 13 , which is coated by a protective pellicle, the coating material making said protective pellicle containing a low water vapour permeability polymer and the weight of said coating material being from 2 to 8% of the weight of the tablet before its coating. 
     
     
         15 . A pharmaceutical composition according to  claim 14 , wherein the coating material further contains a plasticizing agent, a surfactant, and/or a lubricant/glidant. 
     
     
         16 . A method for preventing or treating pulmonary hypertension using a compound of formula I as defined in  claim 1 , or a pharmaceutically acceptable salt, a solvate, a hydrate or a morphological form thereof. 
     
     
         17 . A pharmaceutical composition according to  claim 1  for use as a medicament.