Patent EA-003410-B1 (EA)
Title: Novel form of irbesartan, methods for obtaining said form and pharmaceutical compositions containing them
Inventor: FRANC BRUNO
IPC: A61P27/02
Filed: 1999-06-10
Abstract: 1. A crystalline compound of irbesartan of form A of formula: having a crystal habit such that the ratio between the length and the width of the crystals is between 1:1 and 10:1 and the chargeability of which, measured by tribogeneration, ranges between 0 and -10 nanocoulombs/g. 2. A crystalline compound of irbesartan of form A, in which the ratio between the length and the width of the crystals is between 1:1 and 5:1 and the chargeability of which, measured by tribogeneration, ranges between 0 and -10 nanocoulombs/g. 3. Process for preparing a compound according to Claim 1 or Claim 2, characterized in that of irbesartan acicular habit form A a crystalline suspension is subjected to at least one sonication episode and at least one temperature oscillation episode. 4. Process according to Claim 3, in which the temperature oscillation episode comprises a heating phase and a corresponding cooling phase. 5. Process according to Claim 4, in which the heating phase precedes the cooling phase. 6. Process according to Claim 5, in which the sonication episode is followed by a temperature oscillation episode. 7. Process according to of Claim 3, in which the sonication episode is preceded by a temperature oscillation episode. 8. Process according to Claims 3, in which the sonication episode is carried out simultaneously with the temperature oscillation episode. 9. Process according to Claim 3, in which a sonication episode is carried out between 2 temperature oscillation episodes. 10. Process according to Claim 3, in which the sonication and/or temperature oscillation episodes are repeated independently. 11. Process according to Claim 3, in which the sonication is carried out in batches, semi-continuously or continuously. 12. Process according to Claim 5, in which the heating phase of the temperature oscillation episode is carried out at a temperature of between about 20 degree C and 100 degree C. 13. Process according to Claim 5, in which the heating phase of the temperature oscillation episode is carried out at a temperature such that about 15% to 25% of the crystals are dissolved in about 60 minutes. 14. Process according to Claim 5, in which the cooling phase of the temperature oscillation episode is carried out at a temperature of between about 100 degree C and -20 degree C. 15. Process according to Claim 5, in which the cooling phase of the temperature oscillation episode is carried out at a temperature of between about -5 degree C and 20 degree C. 16. Process according to Claim 5, in which the crystalline suspension is seeded with irbesartan crystals whose ratio between the length and the width is between 1:1 and 10:1. 17. Process for preparing a compound according to Claim 1 or Claim 2, wherein said process contains the steps consisting of: a) preparing a solution of irbesartan acicular habit form A in an alcohol, under concentration and temperature conditions which allow the total solubility of the irbesartan; b) cooling the said solution to a temperature selected as a function of the concentration of the solution, such that the solution is in the metastable zone; c) seeding with irbesartan crystals of brick habit; d) cooling the irbesartan solution to a temperature of between about 20 degree C and 5 degree C; e) subjecting the crystalline suspension thus formed to a mechanical shearing using a shearing machine; f) heating the crystalline suspension to a temperature of between about 40 degree C and 60 degree C to dissolve the fine particles; g) cooling the crystalline suspension to a temperature of between about 20 degree C and 5 degree C; h) filtering off the crystals of brick habit thus formed. 18. Process according to Claim 17, in which, in step a), the irbesartan is dissolved in isopropanol. 19. Process according to Claim 17, in which, in step b), a solution containing 50 g/litre to 70 g/litre of irbesartan in isopropanol is cooled to a temperature ranging between 60 degree C and 80 degree C. 20. Process according to Claim 17, in which, in step c) , the solution is seeded with irbesartan crystals whose ratio between the length and the width is between 1:1 and 10:1. 21. Process according to Claim 20, in which the seeded solution is maintained at a temperature of between 80 degree C and 22 degree C for a few minutes to about 2 hours, before being cooled. 22. Process according to Claim 20, in which, in steps b) and d), the rate of cooling is from about 5 degree C to 20 degree C per hour. 23. Process according to Claim 17, in which, in step e) , the mechanical shearing is carried out by a machine having a spin speed of about from 10 000 rpm to 15 000 rpm. 24. Process according to Claim 23, in which the mechanical shearing in step e) is carried out either by placing the shearing machine directly in the reactor or by passing the crystalline suspension into the shearing machine. 25. Pharmaceutical composition containing a compound according to either of Claims 1 to 3 and pharmaceutically acceptable excipients. 26. Pharmaceutical composition according to Claim 25, containing diuretic agent combined with a compound according to either of Claims 1 to 3. 27. Pharmaceutical composition according to Claim 28, in which the diuretic agent is hydrochlorothiazide.