Dosage forms of risedronate

Abstract

Oral dosage forms of a risedronate comprised of a safe and effective amount of a pharmaceutical composition comprising risedronate, a chelating agent, and, means for effecting delayed release of the risedronate and the chelating agent in the small intestine provide immediate release of the pharmaceutical composition 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 risedronate and food or beverages, which interaction results in the bisphosphonate active ingredient not being available for absorption. The resulting oral dosage form may thus be taken with or without food. Further, the present invention effects 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.

1 . An oral dosage form of a bisphosphonate comprising a safe and effective amount of a pharmaceutical composition comprising:
 (a) from about 1 mg to about 250 mg risedronate;   (b) from about 10 mg to about 970mg of a chelating agent; and   (c) a delayed release mechanism to immediately release the risedronate and the chelating agent in the small intestine; wherein said composition weighs no greater than 1 gram.   
     
     
         2 . The oral dosage form of  claim 1  wherein the chelating agent is at least 50% as soluble in water as the risedronate. 
     
     
         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, malic acid, tartaric acid, lactic acid, lysine, sodium hexametaphosphate, their salts and combinations thereof. 
     
     
         4 . The oral dosage form of  claim 3  wherein the chelating agent is selected from the group consisting of sodium or disodium ethylenediaminetetraacetate, citric acid, sodium hexametaphosphate, and combinations thereof. 
     
     
         5 . The oral dosage form of  claim 4  wherein the chelating agent is disodium EDTA. 
     
     
         6 . The oral dosage form of  claim 1  wherein the means for delayed release of the bisphosphonate and the chelating agent in the small intestine is selected from the group consisting of pH triggered delivery systems, time dependent delivery systems and mixtures thereof. 
     
     
         7 . The oral dosage form of  claim 6  wherein the means for delayed release is a pH triggered delivery system. 
     
     
         8 . The oral dosage form of  claim 7  wherein the pH triggered delivery system comprises an enteric coating which delivers the bisphosphonate and the chelating agent to the small intestine. 
     
     
         9 . The oral dosage form of  claim 8  wherein the enteric coating disintegrates between about pH 5.5 and about pH 6.5. 
     
     
         10 . The oral dosage form of  claim 1  wherein the pharmaceutical composition is comprised of from about 0.5% to about 75% of risedronate and from about 25% to about 99.5% of pharmaceutically-acceptable excipients. 
     
     
         11 . The oral dosage form of  claim 10  wherein the chelating agent is present at an amount of from about 10 mg to about 500 mg. 
     
     
         12 . An oral dosage form comprising a safe and effective amount of a pharmaceutical composition comprising:
 (a) from about 5 mg to about 70 mg risedronate;   (b) from about 25 mg to about 500 mg of disodium EDTA; and   (c) an enteric coating which provides for immediate release of the bisphosphonate and the EDTA in the small intestine of a mammal.   
     
     
         13 . The oral dosage form of  claim 12  wherein the pharmaceutical composition comprises from about 35 mg to about 50 mg of risedronate. 
     
     
         14 . The oral dosage form of  claim 13  wherein the pharmaceutical composition comprises an enteric coating that dissolves at about pH 5.5. 
     
     
         15 . A method for treating or preventing diseases characterized by abnormal calcium and phosphate metabolism comprising administering to a human or other mammal in need thereof a safe and effective amount of a pharmaceutical composition delivered to said human or other mammal via the oral dosage form of  claim 1 . 
     
     
         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. 
     
     
         17 . The method of  claim 16  wherein the disease is osteoporosis. 
     
     
         18 . The method of  claim 17  wherein the oral dosage form is administered according to a continuous schedule having a dosing interval selected from the group consisting of daily, weekly, three times per month, twice monthly, and once monthly. 
     
     
         19 . The method of  claim 18  wherein the oral dosage form is administered weekly. 
     
     
         20 . The method of  claim 19  wherein an oral risedronate is administered to a patient with or without food by dosing a safe and effective amount of a pharmaceutical composition of  claim 13 . 
     
     
         21 . A kit comprising:
 (a) one or more oral dosage forms comprising a risedronate and a chelating agent; and   (b) means for facilitating compliance with the method of  claim 14 .   
     
     
         22 . The kit of  claim 21  further comprising one or more unit doses of a nutrient.