Water-insoluble, iron-containing mixed metal, granular material
There is provided a granular material comprising (i) at least 50% by weight based on the weight of the granular material of solid water-insoluble mixed metal compound capable of binding phosphate of formula (I): M II 1-x M III x (OH) 2 A n- y .ZH 2 O (I) where M II is at least one of magnesium, calcium, lanthanum and cerium; M III is at least iron(III); A n- is at least one n-valent anion; x=Σny; 0<x≦0.67, 0<y≦1, and 0≦z<10; (ii) from 3 to 12% by weight based on the weight of the granular material of non-chemically bound water, and (iii) no greater than 47% by weight based on the weight of the granular material of excipient.
1. A dried granular material comprising granules, each granule comprising a mixture of
(i) at least 50% by weight based on the weight of the granule of solid water-insoluble inorganic mixed metal compound capable of binding phosphate and which contains iron (III) and at least one of magnesium, calcium, lanthanum or cerium, wherein the mixed metal compound is not a hydrothermally-treated compound,
(ii) from 3 to 10% by weight based on the weight of the granule of non-chemically bound water, and
(iii) an excipient, present in an amount no greater than 47% by weight based on the weight of the granule, wherein at least 50% by weight of the granules of the granular material have a diameter of from 106 micrometers to 1180 micrometers.
2. A granular material according to claim 1 wherein the mixed metal compound comprises a layered double hydroxide.
3. A granular material according to claim 1 wherein the mixed metal compound contains at least one of hydroxyl and carbonate ions and contains as the metals iron (III) and magnesium.
4. A granular material according to claim 1 , wherein the granular material comprises from 5 to 20% by weight of pregelatinised starch as excipient based on the weight of the granule.
5. A granular material according to claim 1 , comprising from 1 to 15% by weight of cross linked polyvinyl pyrrolidone as excipient based on the weight of the granule.
6. A granular material according to claim 1 wherein the excipient comprises at least pregelatinised starch and crospovidone.
7. A granular material according to claim 1 wherein at least 95% by weight of the granules of the granular material have a diameter less than 1180 micrometers.
8. A unit dose for oral administration comprising a water resistant capsule containing a granular material according to claim 1 .
9. A unit dose for oral administration comprising a compacted tablet of a granular material according to claim 1 .
10. A unit dose according to claim 9 further comprising a lubricant between the granules.
11. A unit dose according to claim 10 wherein the lubricant is or comprises magnesium stearate.
12. A unit dose according to claim 9 coated with a water-resistant coating.
13. A unit dose according to claim 12 wherein the water-resistant coating comprises at least 30% by weight of a butylated methacrylate copolymer.
14. A unit dose according to claim 12 wherein the tablet has a belly band having a width of 2 mm or more.
15. A unit dose according to claim 8 wherein the solid water-insoluble inorganic compound capable of binding phosphate is present in an amount of at least 200 mg.
16. A process for the preparation of a granular material as defined in claim 1 comprising the steps of:
i) mixing the solid water-insoluble inorganic mixed metal compound with one or more excipients to produce a homogeneous mix,
ii) contacting a suitable liquid with the homogeneous mix and mixing in a granulator to form wet granules,
iii) optionally passing the wet granules though a screen to remove granules lager than the screen size,
iv) drying the wet granules to provide dry granules, and
v) milling and/or sieving the dry granules, wherein at least 50% by weight of the granules of the granular material have a diameter of from 106 micrometers to 1180 micrometers.
17. A process according to claim 16 where in the liquid is selected from water, ethanol and mixtures thereof.
18. A method of treating hyperphosphataemia comprising administering a granular material according to claim 1 to a patient in need thereof.