5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt, hydrate as pharmaceutical

Abstract

A hydrate of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt, characterized in that it: (i) comprises water in the range of from 0.4 to 2.5 %w/w; and (ii) provides an infra red spectrum containing peaks at 1749, 1703, 1645, 1623, 1365 and 736 cm −1 ; and/or (iii) provides an X-ray powder diffraction (XRPD) pattern substantially as set out in Figure II and/or (iv) provides a Raman spectrum containing peaks at 3106, 3069, 3002, 2961, 1750, 1718, 1684, 1385, 1335, 1229, 1078, 917, 428 and 349 cm −1 and/or (iv) provides a solid-state nuclear magnetic resonance spectrum containing chemical shifts substantially as set out in Table I; a process for the preparation of such a compound, a pharmaceutical composition containing such a compound and the use of such a compound or composition in medicine.

1 . A hydrate of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt, characterised in that it: 
 (i) comprises water in the range of from 0.4 to 2.5%w/w; and    (ii) provides an infra red spectrum containing peaks at 1749, 1703, 1645, 1623, 1365 and 736 cm −1 ; and/or    (iii) provides an X-ray powder diffraction (XRPD) pattern substantially as set out in Table I and /or    (iv) provides a Raman spectrum containing peaks at 3106, 3069, 3002, 2961, 1750, 1718, 1684, 1385, 1335, 1229, 1078, 917, 428 and 349 cm −1  and/or    (iv) provides a solid-state nuclear magnetic resonance spectrum containing chemical shifts substantially as set out in Table II.    
     
     
         2 .A hydrate according to  claim 1 , wherein the water content is in the range of from 1.5 to 2.0% w/w.  
     
     
         3 . A hydrate according to  claim 1  or  claim 2 , which provides an infra red spectrum substantially in accordance with Figure I.  
     
     
         4 . A hydrate according to any one of  claims 1  to  3 , which provides an X-ray powder diffraction (XRPD) pattern substantially as set out in accordance with Figure II.  
     
     
         5 . A hydrate according to any one of  claims 1  to  4 , which provides a Raman spectrum substantially as set out in Figure III.  
     
     
         6 . A hydrate according to any one of  claims 1  to  5 , which provides a solid state nuclear magnetic resonance spectrum substantially in accordance with Figure IV.  
     
     
         7 . A hydrate according to any one of  claims 1  to  6 , in isolated form.  
     
     
         8 . A hydrate according to any one of  claims 1  to  7 , in pure form.  
     
     
         9 . A hydrate according to any one of  claims 1  to  8 , in crystalline form.  
     
     
         10 . A compound in the form of a rehydratable form of a hydrate according to any one of  claims 1  to  9 .  
     
     
         11 . A process for preparing a hydrate according to  claim 1 , characterised in that 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt is crystallised from ethanol containing 15 to 25% by volume of water.  
     
     
         12  A pharmaceutical composition comprising an effective, non-toxic amount of a hydrate according to  claim 1  and a pharmaceutically acceptable carrier therefor.  
     
     
         13 . A hydrate according to  claim 1 , for use as an active therapeutic substance.  
     
     
         14 . A hydrate according to  claim 1 , for use in the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof.  
     
     
         15 . The use of Hydrate for the manufacture of a medicament for the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof.  
     
     
         16 . A method for the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof, in a human or non-human mammal which comprises administering an effective, non-toxic, amount of Hydrate to a human or non-human mammal in need thereof.