Process for the preparation of sevelamer hydrochloride and formulation thereof
Disclosed herein is an improved process for preparation of Sevelamer hydrochloride having phosphate binding capacity of 4.7 to 6.4 mmol/g. Further, the invention discloses Sevelamer hydrochloride compositions and a novel process for preparation of said compositions comprising high shear non-aqueous granulation.
1. A process for wet granulating sevelamer, the process comprising the steps of:
a) obtaining sevelamer;
b) mixing said sevelamer with a granulation liquid,
i) said granulation liquid comprised of at least one non-aqueous solvent,
ii) said granulation liquid is further comprised of from 0% to less than about 20% water; and
c) granulating the sevelamer by wet granulation to produce granulated sevelamer.
2. The process of claim 1 , wherein the non-aqueous solvent comprises a short-chain alcohol.
3. The process of claim 2 , wherein the non-aqueous solvent comprises ethyl alcohol.
4. The process of claim 2 , wherein the non-aqueous solvent comprises isopropyl alcohol.
5. The process of claim 4 , wherein said granulation liquid is further comprised of about 5% water.
6. The process of claim 1 , wherein the granulation liquid further comprises a binder.
7. The process of claim 6 , wherein said binder comprises polyvinylpyrrolidone.
8. The process of claim 1 , wherein before the sevelamer is mixed with the granulation liquid, the sevelamer is pre-wet with a wetting solution.
9. The process of claim 8 , wherein the wetting solution comprises water.
10. The process of claim 9 , wherein the wetting solution further comprises polyethylene glycol.
11. The process of claim 1 , wherein the granulated sevelamer has a hydration of not more than about 7% as measured by Karl Fischer analysis.
12. The process of claim 1 , wherein the granulated sevelamer exhibits a weight loss on drying of not more than about 15%.
13. The process of claim 2 , wherein the granulating is selected from the group consisting of: wet high-shear granulation and wet spray granulation.
14. A composition of matter comprising sevelamer prepared by the process of claim 1 .
15. The composition of matter of claim 14 , further comprising at least one pharmaceutically-acceptable excipient, said composition in oral tablet form, said tablet providing up to about 1 gram of sevelamer per tablet, said tablet substantially disintegrating in HCl solution within not more than about 3 minutes.
16. In a process of granulating sevelamer, the improvement comprising wet granulation using a granulation liquid comprised of at least one non-aqueous solvent and from 0% to less than about 20% water, whereby the sevelamer may be wet granulated using the granulation liquid.
17. Sevelamer, wet granulated with a granulation liquid comprised of at least one non-aqueous solvent and from 0% to less than about 20% water.