MODIFIED-RELEASE PHARMACEUTICAL FORMULATIONS CONTAINING DEFERIPRONES

Claims

1. A pharmaceutical formulation in the form of modified-release tablets coated with an enteric coating for oral administration twice a day, wherein the tablet core contains: a) deferiprone in an amount of 85.0 to 95.0%, b) a hydroxypropyl methylcellulose-based polymer having a viscosity of 100 cP alone or in a mixture with a hydroxypropyl methylcellulose-based polymer having a viscosity of 4000 cP as a release-modifying agent, in an amount of 4.0 to 10.0%, c) a lubricant and / or glidant in an amount of 0.2 to 2.0% and d) other suitable pharmaceutically acceptable excipients in an amount of 0 to 5%, all amounts are calculated by weight based on the total weight of the formulation.

2. The pharmaceutical composition according to claim 1, wherein the release-modifying agent consists of a polymer based on hydroxypropyl methylcellulose having a viscosity of 100 cP, in an amount of 7.5 wt.%.

3. The pharmaceutical composition according to claim 1, wherein the release-modifying agent consists of a mixture of a hydroxypropyl methylcellulose-based polymer having a viscosity of 100 cP, alone or in a mixture with a hydroxypropyl methylcellulose-based polymer having a viscosity of 4000 cP, in an amount of 5 wt.%.

4. The pharmaceutical composition according to claim 3, wherein the ratio between the two polymers is 40:60 wt. / wt.%.

5. The pharmaceutical composition according to any one of the preceding claims, wherein the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc and combinations thereof.

6. The pharmaceutical composition according to claim 5, wherein the lubricating agent is magnesium stearate.

7. A pharmaceutical composition according to any one of the preceding claims, wherein the glidant is selected from the group consisting of colloidal silicon dioxide, starch and talc and combinations thereof.

8. The pharmaceutical composition according to claim 7, wherein the glidant is colloidal silicon dioxide.

9. A pharmaceutical composition according to any one of the preceding claims, wherein other suitable pharmaceutically acceptable excipients are selected from the classes of pH adjusting agents and bulking agents.

10. A pharmaceutical composition according to any one of the preceding claims, wherein the enteric coating comprises an enteric polymer, a diluent and, optionally, a plasticizer.

11. The pharmaceutical composition according to claim 10, wherein the enteric coating comprises a dispersion of a copolymer of ethacrynic acid and ethyl acrylate (1:1) in water and propylene glycol.

12. The pharmaceutical composition according to claim 10, wherein the enteric coating comprises a copolymer of methacrylic acid and methacrylate (1:1) in an alcohol solution with triethyl citrate.

13. A pharmaceutical composition according to any of the preceding claims, wherein the tablet core contains from 500 to 1500 mg of deferiprone.

14. The pharmaceutical composition according to claim 13, wherein the tablet core contains 1000 mg of deferiprone.

15. A pharmaceutical composition according to any of the preceding claims which is suitable for administration twice daily.

16. A method for producing a pharmaceutical composition according to any one of paragraphs 1-15, comprising the following steps: (i) mixing deferiprone with a release-modifying agent and other pharmaceutically acceptable excipients, if present, to form a mixture; (ii) wet granulating the mixture obtained in step (i) in a high shear granulator followed by drying and screening to obtain a granulate; (iii) mixing the granulate obtained in step (ii) with a lubricating excipient and / or glidant to form a mixture; compressing the mixture obtained in step (iii) to form a tablet; (iv) coating the tablet.

17. A method for producing a pharmaceutical composition according to any one of paragraphs 1-15, comprising the following steps: (i) mixing deferiprone with a release-modifying agent and other pharmaceutically acceptable excipients, if present, to form a mixture; (ii) adding a lubricating excipient and / or glidant and further mixing; (iii) directly compressing the mixture obtained in step (ii) to form a tablet; (iv) coating the tablet.

18. A pharmaceutical composition according to any one of claims 1-15 for use in the treatment of diseases causing iron overload, or for the prevention and / or treatment of diseases caused by iron overload.

19. A pharmaceutical composition for use according to claim 18, wherein the disease is thalassemia or sickle cell anemia.

20. A pharmaceutical composition for use according to claim 18, wherein said iron overload is transfusion iron overload resulting from a blood transfusion.