Pharmaceutical formulation comprising lanthanum compounds

• US 7,465,465 B2
• Filed: 08/26/2004
• Issued: 12/16/2008
• Est. Priority Date: 08/26/2003
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Shire BioChem, Inc. (Shire plc)
• Inventors: Ferdinando, Josephine Christine, Haslam, Robert Paul, Trespidi, Laura Anna
• Primary Examiner(s): Richter; Johann R
• Assistant Examiner(s): Arnold; Ernst V
• Application Number:
  US10/926,330
• Publication Number:
  US 20050079135A1
• Time in Patent Office: 1,573 Days
• Field of Search: 424/464, 424/715, 514/960, 514/492
• US Class Current: 424/600
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

This invention relates to a chewable lanthanum formulation comprising a pharmaceutically effective amount of a lanthanum compound; and at least one chewable pharmaceutically acceptable excipient. This invention also relates to a pharmaceutical formulation in a tablet or in a powder comprising a pharmaceutically effective amount of a lanthanum compound produced by a process which comprises the steps of: a) powder blending the lanthanum compound and at least one pharmaceutically acceptable excipient in a mixer to form a mixture; or b) powder blending the lanthanum compound and excipients, compressing the resulting combination into a slug material or roller compacting the resulting combination into a strand material, and milling the prepared material into a free flowing mixture; and c) compressing the resulting mixture into a tablet or filing up the resulting mixture in a appropriate container.

Claims

1. A lanthanum carbonate pharmaceutical formulation in a chewable tablet, comprising lanthanum carbonate in an amount of from about 200 mg to about 1000 mg elemental lanthanum in the proportion of about 10 to about 40 wt % of the formulation as elemental lanthanum and pharmaceutically acceptable excipients comprising a diluent in an amount from about 40 to about 80 wt % of the formulation and a flow agent in an amount from about 0.1 to about 5.0 wt % of the formulation, produced by a process which comprises the steps of:

a. blending the lanthanum carbonate and the pharmaceutically acceptable excipients to form a mixture;

or

b. blending the lanthanum carbonate and the pharmaceutically acceptable excipients, compressing the resulting combination into a slug material or roller compacting the resulting combination into a strand material, and milling the prepared material into a free flowing mixture; and

c. compressing the mixture formed in steps a or b into a tablet,

wherein the process is performed without wet granulation or drying, the diluent is dextrates, corn syrup, oligosaccharide, isomaltooligosaccharide, glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose, dextrin, starch, fructose, xylitol, maltodextrin, maltitol, isomalt, lactose, sorbitol, microcrystalline cellulose, sucrose based diluent-binders, confectioner'"'"'s sugar, calcium sulfate dihydrate, calcium lactate trihydrate, hydrolysed starches, dextrose, inositol, hydrolyzed cereal solids, amylase, or glycine, and the flow agent is magnesium stearate, talc, polyethylene glycol, silica, colloidal anhydrous silica, hydrogenated vegetable oils, glyceryl behenate, or glyceryl monostearate.

3. The formulation of claim 1, wherein the lanthanum carbonate has the formula:

La₂(CO₃)₃.xH₂O

where x has a value from 3 to 8.

4. The formulation of claim 3, wherein x has a value from about 4 to about 5.

5. The formulation of claim 1, wherein the diluent is dextrates or sorbitol.

6. The formulation of claim 1, wherein the flow agent is colloidal anhydrous silica in an amount of about 2 wt % of the formulation.

7. The chewable lanthanum carbonate pharmaceutical tablet of claim 1 for the treatment of chronic renal insufficiency, comprising the following ingredients:

8. The chewable lanthanum carbonate pharmaceutical tablet of claim 1 for the treatment of chronic renal insufficiency comprising the following ingredients:

11. The formulation of claim 1, produced by the process which comprises the steps of:

a. blending the lanthanum carbonate and the pharmaceutically acceptable excipients to form a mixture; and

b. compressing the mixture into a tablet.

12. The lanthanum carbonate pharmaceutical formulation of claim 1, wherein the lanthanum carbonate is in an amount from about 20 to about 30 wt % lanthanum, as the element.

2. A lanthanum carbonate pharmaceutical formulation in a chewable tablet, comprising lanthanum carbonate in an amount of from about 200 mg to about 1000 mg elemental lanthanum in the proportion of about 10 to about 40 wt % of the formulation as elemental lanthanum and pharmaceutically acceptable excipients comprising a diluent in an amount from about 40 to about 80 wt % of the formulation and a flow agent in an amount from about 0.1 to about 5.0 wt % of the formulation, produced by a process which comprises the steps of:

a. compressing the lanthanum carbonate into a slug material or roller compacting the lanthanum carbonate into a strand material,

b. milling the slug or strand material into a free flowing material,

c. blending the free flowing material with the pharmaceutically acceptable excipients to form a mixture, and

d. compressing the mixture into a tablet,

wherein the process is performed without wet granulation or drying, the diluent is dextrates, corn syrup, oligosaccharide, isomaltooligosaccharide, glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose, dextrin, starch, fructose, xylitol, maltodextrin, maltitol, isomalt, lactose, sorbitol, microcrystalline cellulose, sucrose based diluent-binders, confectioner'"'"'s sugar, calcium sulfate dihydrate, calcium lactate trihydrate, hydrolysed starches, dextrose, inositol, hydrolyzed cereal solids, amylase, or glycine, and the flow agent is magnesium stearate, talc, polyethylene glycol, silica, colloidal anhydrous silica, hydrogenated vegetable oils, glyceryl behenate, or glyceryl monostearate.

9. A lanthanum carbonate pharmaceutical formulation in a powder, comprising lanthanum carbonate in an amount of from about 200 mg to about 1000 mg elemental lanthanum in the proportion of about 10 to about 40 wt % of the formulation as elemental lanthanum and pharmaceutically acceptable excipients comprising a diluent in an amount from about 40 to about 80 wt % of the formulation and a flow agent in an amount from about 0.1 to about 5.0 wt % of the formulation, produced by a process which comprises the steps of:

a. blending the lanthanum carbonate and the pharmaceutically acceptable excipients,

b. compressing the resulting combination into a slug material or roller compacting the resulting combination into a strand material, and

c. milling the prepared material into a free flowing powder mixture,

wherein the process is performed without wet granulation or drying, the diluent is dextrates, corn syrup, oligosaccharide, isomaltooligosaccharide, glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose, dextrin, starch, fructose, xylitol, maltodextrin, maltitol, isomalt, lactose, sorbitol, microcrystalline cellulose, sucrose based diluent-binders, confectioner'"'"'s sugar, calcium sulfate dihydrate, calcium lactate trihydrate, hydrolysed starches, dextrose, inositol, hydrolyzed cereal solids, amylase, or glycine, and the flow agent is magnesium stearate, talc, polyethylene glycol, silica, colloidal anhydrous silica, hydrogenated vegetable oils, glyceryl behenate, or glyceryl monostearate.

10. A lanthanum carbonate pharmaceutical formulation in a powder comprising, lanthanum carbonate in an amount of from about 200 mg to about 1000 mg elemental lanthanum in the proportion of about 10 to about 40 wt % of the formulation as elemental lanthanum and pharmaceutically acceptable excipients comprising a diluent in an amount from about 40 to about 80 wt % of the formulation and a flow agent in an amount from about 0.1 to about 5.0 wt % of the formulation, produced by a process which comprises the steps of:

a. compressing the lanthanum carbonate into a slug material or roller compacting the lanthanum carbonate into a strand material,

b. milling the slug or strand material into a free flowing material, and

c. blending the free flowing powder material with the pharmaceutically acceptable excipients to form a mixture,

wherein the process is performed without wet granulation or drying, the diluent is dextrates, corn syrup, oligosaccharide, isomaltooligosaccharide, glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose, dextrin, starch, fructose, xylitol, maltodextrin, maltitol, isomalt, lactose, sorbitol, microcrystalline cellulose, sucrose based diluent-binders, confectioner'"'"'s sugar, calcium sulfate dihydrate, calcium lactate trihydrate, hydrolysed starches, dextrose, inositol, hydrolyzed cereal solids, amylase, or glycine, and the flow agent is magnesium stearate, talc, polyethylene glycol, silica, colloidal anhydrous silica, hydrogenated vegetable oils, glyceryl behenate, or glyceryl monostearate.