Patent EA-004534-B1 (EA)
Title: Novel pharmaceutical
Inventor: BLACKLER PAUL DAVID JAMES
IPC: A61K31/00
Filed: 2000-04-19
Abstract: 1. A polymorphic form of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl] thiazolidine-2,4-dione, maleic acid salt (the "Polymorph") characterised in that it: (i) provides an infra red spectrum containing peaks at 1360, 1326, 1241, 714 and 669 cm<-1>; and/or (ii) provides a Raman spectrum containing peaks at 1581, 768, 670, 271 and 226 cm<-1>; and/or (iii) provides a solid-state nuclear magnetic resonance spectrum containing peaks at chemical shifts substantially as set out in Table I; and/or (iv) provides an X-ray powder diffraction (XRPD) pattern containing peaks substantially as set out in Table II. 2. A Polymorph according to claim1, which provides an infra red spectrum substantially in accordance with Figure I. 3. A Polymorph according to claim 1 or claim 2, which provides a Raman spectrum substantially in accordance with Figure II. 4. A Polymorph according to any on of claims 1 to 3, which provides a solid-state nuclear magnetic resonance spectrum substantially in accordance with Figure III. 5. A Polymorph according to any one of claims 1 to 4, which provides an X-ray powder diffraction (XRPD) pattern substantially in accordance with Figure IV. 6. A Polymorph according to any one of claims 1 to 5, in isolated form. 7. A Polymorph according to any one of claims 1 to 6, in pure form. 8. A process for preparing a Polymorph according to claim1, characterised in that: (a) a slurry of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt (hereinafter also referred to as "Compound (I)" or the "Original Polymorph") in aqueous ethanol containing up to about 2.5% w/v water, is heated for an extended period of time; after which time the Polymorph is recovered from the denatured ethanol; or (b) Compound (I) is admixed with denatured ethanol, heated to an elevated temperature, over an extended period of time, after which time the Polymorph is recovered from the solvent; or (c) Compound (I) in denatured ethanol containing up to 2.5% w/v water at 55 degree C is seeded with the Polymorph then cooled to a temperature in the range of from 20 degree C to 25 degree C to provide the Polymorph; the Polymorph is then recovered from the solvent. 9. A pharmaceutical composition comprising an effective, non-toxic amount of a Polymorph according to claim 1 and a pharmaceutically acceptable carrier therefor. 10. A process for preparing a Compound (I), which is 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, maleic acid salt, which process comprises: (i) first preparing a solution of the Polymorph in a mixture (100:1 v/v) of absolute ethanol and methanol at an elevated temperature, (ii) then allowing the solution to cool to ambient temperature, (iii) allowing it to crystallise; and (iv) isolating crystals of Compound (I). 11. The process according to claim 10 further comprises the step of in which the cooled solution may be seeded with Compound (I). 12. The process according to claim 10 or 11, in which the elevated temperature is between 60 to 75 degree C. 13. The process according to any one of claims 10-12, in which cooling to an ambient temperature is cooling to 20-25 degree C. 14. The process according to any one of claims 10-13, in which step (i) further comprises the step of the solution filtering at an elevated temperature.