Low dosage forms of risedronate or its salts

Abstract

Oral dosage forms comprising risedronate or a salt thereof, a chelating agent, and means for effecting delayed release of the risedronate (or salt) immediate release of the oral dosage form to the small intestine of the mammal subject and pharmaceutically effective absorption of the bisphosphonate with or without food or beverages. The present invention substantially alleviates the interaction between the risedronate (or salt) and food or beverages, which interaction results in the active ingredient not being available for absorption. The resulting oral dosage form may thus be taken with or without food. Further, disclosed is delivery of risedronate and the chelating agent to the small intestine, substantially alleviating the upper GI irritation associated with bisphosphonate therapies. These benefits simplify previously complex treatment regimens and can lead to increased patient compliance with bisphosphonate therapies.

What is claimed is: 
     
         1 . An oral dosage form comprising:
 (a) from about 50 mg to less than 150 mg of a bisphosphonate selected from the group consisting of risedronate and salts thereof;   (b) from about 10 mg to about 1000 mg of a chelating agent; and   (c) a delayed release mechanism to immediately release the bisphosphonate and the chelating agent in the small intestine.   
     
     
         2 . The oral dosage form of  claim 1  wherein the bisphosphonate is risedronate sodium. 
     
     
         3 . The oral dosage form of  claim 2  wherein the chelating agent is selected from the group consisting of sodium or disodium ethylenediaminetetraacetate, citric acid, sodium hexametaphosphate, salts thereof, and combinations thereof. 
     
     
         4 . The oral dosage form of  claim 3  wherein the chelating agent is disodium EDTA. 
     
     
         5 . The oral dosage form of  claim 2  wherein the delayed release mechanism is selected from the group consisting of pH triggered delivery systems, time dependent delivery systems and mixtures thereof. 
     
     
         6 . The oral dosage form of  claim 5  wherein the delayed release mechanism is a pH triggered delivery system. 
     
     
         7 . The oral dosage form of  claim 6  wherein the pH triggered delivery system comprises an enteric coating. 
     
     
         8 . The oral dosage form of  claim 4  wherein the delayed release mechanism comprises methacrylic acid copolymer. 
     
     
         9 . The oral dosage form of  claim 4  comprising from about 55 mg to about 500 mg of the disodium EDTA. 
     
     
         10 . The oral dosage form of  claim 9  comprising from about 75 mg to about 250 mg of the disodium EDTA. 
     
     
         11 . The oral dosage form of  claim 10  comprising about 100 mg of the risedronate sodium. 
     
     
         12 . The oral dosage form of  claim 10  wherein the delayed release mechanism comprises a methacrylic acid copolymer. 
     
     
         13 . The oral dosage form of  claim 12  comprising about 100 mg of the risedronate sodium. 
     
     
         14 . The oral dosage form of  claim 13  comprising about 100 mg of the disodium EDTA. 
     
     
         15 . A method for treating a disease characterized by abnormal calcium and phosphate metabolism comprising administering to a human or other mammal in need thereof the oral dosage form of  claim 2 . 
     
     
         16 . The method of  claim 15  wherein the disease is selected from the group consisting of osteoporosis, Paget's disease, hyperparathyroidism, hypercalcemia of malignancy, and osteolytic bone metastasis, and combinations thereof. 
     
     
         17 . The method of  claim 16  comprising treatment of osteoporosis. 
     
     
         18 . The method of  claim 17  wherein the oral dosage form is administered continuously on a monthly basis. 
     
     
         19 . The method of  claim 18  wherein the oral dosage form is administered with or without food. 
     
     
         20 . The method of  claim 18  wherein the oral dosage form comprises about 100 mg of risedronate sodium. 
     
     
         21 . The method of  claim 20  wherein the oral dosage form comprises about 100 mg of disodium EDTA.