Lanthanum composition
The present invention discloses stable, solid oral pharmaceutical composition comprising Lanthanum carbonate having more than 6 molecules of water per molecule of lanthanum carbonate and pharmaceutically acceptable carriers or diluents, wherein said carrier or diluent excludes monosaccharide/s or disaccharide/s, such that the composition has comparable in-vitro dissolution profile similar to that of FOSRENOL®. Also disclosed is a wet granulation process for making the same.
1. A stable wet granulated pharmaceutical composition in the form of a tablet for human use comprising:
a) more than 70% weight by weight of lanthanum carbonate octahydrate; and
b) a pharmaceutically acceptable diluent or carrier excluding monosaccharide(s) and disaccharide(s);
wherein the composition does not exhibit decarboxylation of lanthanum carbonate after three months of storage at 40° C. and 75% humidity.
2. The composition according to claim 1 , wherein said diluent or carrier is selected from the group consisting of microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose and mixtures thereof.
3. The composition according to claim 1 , wherein said lanthanum carbonate octahydrate has a particle size distribution such that the d (0.9) is not more than 110 microns.
4. The composition according to claim 1 , wherein said composition further contains one or more pharmaceutically acceptable excipients selected from the group consisting of binders, disintegrants, sweeteners, flavors, surfactants, glidants, lubricants and mixtures thereof.
5. The composition according claim 4 , wherein said binder is selected from a group consisting of methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, gelatin, polyvinylpyrrolidone, poly(meth)acrylates, and mixtures thereof.
6. A process for preparing a wet granulated lanthanum carbonate composition in the form of a stable tablet containing more than 70% w/w of lanthanum carbonate octahydrate, wherein said process comprises the steps of:
a) blending lanthanum carbonate octahydrate, with at least one diluent or carrier and optionally other pharmaceutically acceptable excipients to form a blend;
b) granulating the blend of step (a) with a binder solution to foam granules;
c) optionally, blending the granules of step (b) with one or more lubricants, and/or one or more extra granular ingredients to get a final blend; and
d) compressing said final blend to form tablets; wherein said diluent or carrier excludes monosaccharides and disaccharides and wherein the composition does not exhibit decarboxylation of lanthanum carbonate after three months of storage at 40° C. and 75% humidity.
7. The process according to claim 6 , wherein said binder solution comprises at least one binder dissolved/dispersed in a granulating fluid.
8. The process according to claim 6 , wherein said diluent or carrier is selected from the group consisting of microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose and mixtures thereof.
9. The process according to claim 6 , wherein said lanthanum carbonate octahydrate has a particle size distribution such that the d (0.9) is not more than 110 microns.
10. The process according to claim 7 , wherein said binder is selected from a group consisting of methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl-cellulose, sodium carboxymethyl cellulose, gelatin, polyvinylpyrrolidone, poly(meth)acrylates, and mixtures thereof.
11. The process according to claim 6 , wherein said composition optionally contains one or more pharmaceutically acceptable excipients selected from the group consisting of disintegrants, sweeteners, flavors, surfactants, glidants, and mixtures thereof.
12. A stable wet granulated lanthanum carbonate composition in the form of a tablet comprising more than 70% w/w of lanthanum carbonates octahydrate, 5 to 25% w/w of microcrystalline cellulose, 0 to 5% w/w of hydroxypropyl cellulose and 0 to 10% w/w of powdered cellulose, wherein the composition excludes monosaccharides and disaccharides, and wherein the composition does not exhibit decarboxylation of lanthanum carbonate after three months storage at 40° C. and 75% humidity.
13. The composition according to claim 12 , wherein said composition comprises more than 70% w/w of lanthanum carbonates octahydrate, from about 8 to about 15% w/w of microcrystalline cellulose, from about 1 to about 3% w/w of hydroxypropyl cellulose and 0 to about 10% w/w of powdered cellulose.
14. The composition according to claim 13 , wherein said composition further comprises from about 0.5 to about 1.5% w/w of acesulfame potassium and from about 2 to about 4% of Avicel CE15.