Solid pharmaceutical fixed dose compositions comprising irbesartan and amlodipine, their preparation and their therapeutic application

1. A stable solid oral pharmaceutical fixed dose composition in the form of a monolayer tablet comprising irbesartan, amlodipine besilate and pharmaceutically acceptable excipients, wherein the irbesartan is present as coated granules embedded in an extragranular matrix comprising amlodipine besilate, wherein the amlodipine besilate is not in granular form, and wherein the composition has less than 1.50% (w/w) of total impurities for amlodipine and less than 0.50% (w/w) of total impurities for irbesartan after 6 months at 40° C./75% relative humidity.

2. The composition according to claim 1 , wherein the tablet is film coated.

3. The composition according to claim 2 wherein the tablet is further packaged in suitable packing material.

4. The composition according to claim 1 wherein the irbesartan represents between about 20% and about 70% by weight of the total composition.

5. The composition according to claim 1 wherein the amlodipine besilate represents between about 1% and 20% by weight of the total composition.

6. The composition according to claim 1 wherein the pharmaceutically acceptable excipients are selected from the group consisting of diluent, disintegrant, antiadherent, binder, lubricant, and mixtures thereof.

7. The composition according to claim 1 wherein said solid composition is free of lactose.

8. The composition according to claim 1 wherein the amount of irbesartan is between 150 mg and 300 mg of the total weight of the tablet.

9. The composition according to claim 1 wherein the amount of amlodipine besilate is between 5 mg and 10 mg of the total weight of the tablet.

10. The composition according to claim 1 in the form of a tablet wherein the total weight of the tablet is between 400 mg and 600 mg.

11. A process for the preparation of the composition of claim 1 , wherein the process comprises the steps of:

i. granulating irbesartan and one or more pharmaceutically acceptable excipients with aqueous solution containing a binder to form granules;

ii. drying the granules;

iii. separately blending amlodipine besilate with pharmaceutically acceptable excipients;

iv. mixing the irbesartan granules of step iii with the amlodipine besilate blend of step iii;

v. lubricating the blend of step iv), optionally after a pre-lubricating step; and

vi. compressing the mixture into tablets.

12. The process according to claim 11 wherein the group of pharmaceutically acceptable excipients used in step i) and iii) of the process is free of lactose.

13. The process according to claim 11 further comprising the step of coating the tablet and packaging in suitable packing material.

14. The process according to claim 11 wherein the pre-lubricating step comprises the mixing of the blend of step iv) 10 to 25 min before doing the lubricating step.

15. The composition according to claim 3 wherein said suitable packing material is PVC, PVC/PVdC or PVC/PE/PVdC.

16. The composition according to claim 1 wherein the amount of irbesartan is 300 mg of the total weight of the tablet.

17. The solid composition according to claim 1 wherein the amount of irbesartan is 150 mg of the total weight of the tablet.

18. The solid composition according to claim 1 wherein the amount of amlodipine besilate is 7 mg.

19. The solid composition according to claim 1 wherein the amount of amlodipine besilate is 14 mg.

20. The solid composition according to claim 1 in the form of a tablet wherein the total weight of the tablet is 500 mg.

21. The process according to claim 11 wherein the pre-lubricating step comprises the mixing of the blend of step iv) 20 min before doing the lubricating step.