Phosphate-binding polymer and tablets using the same

• US 20070190135A1
• Filed: 03/12/2007
• Published: 08/16/2007
• Est. Priority Date: 10/12/1998
• Status: Abandoned Application

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Kubota, Ryuji, Matsuda, Katsuya, Takata, Noriyuki
• Application Number:
  US11/716,676
• Publication Number:
  US 20070190135A1
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 13/12 of the kidneys

Abstract

Disclosed are a phosphate-binding polymer having a true specific gravity of 1.18-1.24, tablets that solely consist of the particles of a phosphate-binding polymer having an average particle size of no more than 400 μm, with at least 90% being occupied by particles no larger than 500 μm, and having a true specific gravity of 1.18-1.24 and a water content of 1-14%, or tablets that contain both the particles and crystalline cellulose and/or low substituted hydroxypropyl cellulose, and a process for producing such tablets. The phosphate-binding polymer can be formulated as tablets either alone or in combination with specified additives. Whichever the case, the tablets have satisfactory hardness, contain the active ingredient in high proportion, have high phosphate-binding capability and exhibit rapid disintegrability in an acidic to neutral region while having little sensitivity to the strength of agitation. The tablets are excellent pharmaceutical preparations that undergo reduced variations in bioavailability in spite of movements within the digestive tracts and pH changes.

Claims

1. A tablet having a hardness of 6 KP or more which comprises:

a. particles of a phosphate-binding polymer having an average particle size of no more than 400 microns, with at least 90% of the particles being occupied by particles no larger than 500 microns, and having a true specific gravity of 1.20-1.22 and a water content of 1-14%; and

b. at least one of crystalline cellulose or low substituted hydroxypropyl cellulose wherein the crystalline cellular or the low substituted hydroxypropyl cellulose or mixture thereof is present in an amount of at least 10% of the weight of the phosphate-binding polymer.

2. The tablet according to claim 1 wherein said particles of a phosphate-binding polymer have an average particle size of no more than 250 microns, with at least 90% being occupied by particles no larger than 300 microns.

3. The tablet according to claim 1 wherein the low substituted hydroxypropyl cellulose has 5.0-16.0 wt % substitution by hydroxypropoxyl groups.

4. The tablet according to any of claims 1-3 wherein the phosphate-binding polymer particles are obtained by allowing epichlorohydrin to act on polyallylamine in a water/acetonitrile mixed solvent system so that the polyallylamine is crosslinked.

5. The tablet according to claim 1 wherein further contains a hardened oil.

6. The tablet according to claim 1 which is coated on the surface with a water-soluble film base.

15. A method for treating hyperphosphatemia comprising administering a tablet according to claim 1 to a patient in need thereof.

16. The tablet according to claim 1, wherein the hardness of the tablet is measured with a tablet hardness tester.

17. The tablet according to claim 1, wherein said tablet has a weight loss of 1% or less in a friability test.

18. The tablet according to claim 17, wherein the weight loss of said tablet is measured by a friability tester by being revolved 100 times.

20. The tablet according to claim 1 wherein said table has a weight loss of 1% or less in a friability test.

21. The tablet according to claim 20 wherein the weight loss of said tablet is measured by a friability tester by being revolved 100 times.

7. A process for producing a phosphate-binding polymer tablet having a hardness of 6 KP or more which comprises:

a. grinding a phosphate-binding polymer having a true specific gravity of 1.20-1.22 into particles having an average particle size of no more than 400 microns, with at least 90% being occupied by particles no larger than 500 microns, said phosphate-binding polymer being either polyallylamine or obtained by crosslinking the same;

b. adjusting the phosphate-binding polymer particles to have a water content of 1-14%;

c. mixing the particles with at least one of crystalline cellulose or low substituted hydroxyproply cellulose, wherein the amount of the crystalline cellular, low substituted hydroxypropyl cellulose or mixture thereof is at least 10% by weight of phosphate binding polymer; and

d. compressing the mixture into tablets.

8. The process according to claim 7 wherein the polymer particles have an average particle size of no more than 400 microns, with at least 90% of the particles no larger than 500 microns, and with a water content of 1-14%.

9. The process according to claim 8 wherein the polymer particles have an average particle size of no more than 250 microns, with at least 90% of the particles no larger than 300 microns.

10. The process according to claim 7 which further contains a component selected from the group consisting of crystalline cellulose, low substituted hydroxypropyl cellulose, and mixtures thereof.

11. The process according to claim 7 wherein the low substituted hydroxypropyl cellulose has 5.0-16.0 weight % substitution by hydroxy groups.

12. The process according to claim 7 wherein the tablet further contains a hardened oil.

13. The process according to claim 7 wherein the tablet is coated with a water-soluble film base.

14. The process according to claim 7 wherein the phosphate-binding polymer particles are obtained by allowing epichlorohydrin to act on polyallylamine in a water/acetonitrile mixed solvent system so that the polyallylamine is crosslinked.

19. The process according to claim 7, wherein the hardness of the tablet is measured with a tablet hardness tester.