Capsule and powder formulations containing lanthanum compounds

Abstract

The present invention includes an oral pharmaceutical capsule comprising a shell, lanthanum carbonate or lanthanum carbonate hydrate, and a lubricant such as talc, wherein the shell encapsulates the lanthanum carbonate or its hydrate and the lubricant. Capsule shells comprise, for example, gelatin. The present invention also includes an oral pharmaceutical powder comprising lanthanum carbonate or lanthanum carbonate hydrate and a pharmaceutically acceptable excipient. The oral pharmaceutical capsules and powders of the present invention can be administered to treat a patient at risk of or suffering from hyperphosphatemia, at risk of or suffering from chronic kidney disease (CKD), at risk of or suffering from soft tissue calcification associated with CKD, or at risk of or suffering from secondary hyperparathyroidism.

1 . An oral pharmaceutical capsule comprising a shell, lanthanum carbonate or lanthanum carbonate hydrate, and a lubricant, wherein the shell encapsulates the lanthanum carbonate or lanthanum hydrate and the lubricant. 
     
     
         2 .- 40 . (canceled) 
     
     
         41 . An oral pharmaceutical powder comprising (1) lanthanum carbonate or lanthanum carbonate hydrate, (2) dextrates, (3) colloidal silicon dioxide, and (4) magnesium stearate, wherein the elemental lanthanum as lanthanum carbonate or lanthanum carbonate hydrate is in an amount from about 26 wt % to about 50 wt % by weight of the powder. 
     
     
         42 . The powder of  claim 41 , wherein the lanthanum carbonate or lanthanum carbonate hydrate has the formula:
   La 2 (CO 3 ) 3   .n H 2 O   
       wherein n has a value from 0 to 10. 
     
     
         43 . The powder of  claim 41 , wherein n has a value from 3 to 6. 
     
     
         44 . The powder of  claim 41 , wherein the elemental lanthanum as lanthanum carbonate or lanthanum carbonate hydrate is in an amount from about 35 wt % to about 50 wt % by weight of the powder. 
     
     
         45 . The powder of  claim 41 , wherein the dextrates is in an amount from about 5% to about 50% by weight of the powder. 
     
     
         46 . The powder of  claim 41 , wherein the colloidal silicon dioxide is in an amount from about 0.1% to about 4% by weight of the powder. 
     
     
         47 . The powder of  claim 41 , wherein systemic exposure to lanthanum is higher following administration of the powder compared to administration of a tablet comprising (1) lanthanum carbonate or lanthanum carbonate hydrate, (2) dextrates, (3) colloidal silicon dioxide, and (4) magnesium stearate while the powder and the tablet are pharmacodynamically equivalent. 
     
     
         48 . The powder of  claim 41  comprising (1) 68.14 wt % lanthanum carbonate tetrahydrate, (2) 30.56 wt % dextrates (hydrated), (3) 1.0 wt % colloidal silicon dioxide, and (4) 0.3 wt % magnesium stearate. 
     
     
         49 . A method of treating hyperphosphatemia in a patient comprising administering to the patient an oral pharmaceutical powder comprising (1) lanthanum carbonate or lanthanum carbonate hydrate, (2) dextrates, (3) colloidal silicon dioxide, and (4) magnesium stearate, wherein the elemental lanthanum as lanthanum carbonate or lanthanum carbonate hydrate is in an amount from about 26 wt % to about 50 wt % by weight of the powder. 
     
     
         50 . A method of treating a patient (1) at risk of or suffering from chronic kidney disease (CKD), (2) at risk of or suffering from soft tissue calcification associated with chronic kidney disease (CKD), or (3) at risk of or suffering from secondary hyperparathyroidism comprising administering to the patient an oral pharmaceutical powder comprising (1) lanthanum carbonate or lanthanum carbonate hydrate, (2) dextrates, (3) colloidal silicon dioxide, and (4) magnesium stearate, wherein the elemental lanthanum as lanthanum carbonate or lanthanum carbonate hydrate is in an amount from about 26 wt % to about 50 wt % by weight of the powder.