Oral pharmaceutical formulation containing ibandronate

Abstract

The invention is directed to well-tolerated pharmaceutical compositions for oral application, containing ibandronate or a physiologically tolerable salt thereof as active substance, the administration form consisting of an active substance-containing inner portion enclosed in such fashion by a coat free of active substance that rapid release of the active substance takes place.

1 - 20 . (canceled)  
     
     
         21 . A method of treating a bone disease in a patient in need thereof, comprising orally administering to the patient a pharmaceutical formulation comprising 
 (a) a core containing a bone disease treating effective amount of ibandronate and    (b) a coating which is free of ibandronate,    wherein the coating dissolves or is separated from the core during contact with digestive solution in the patient's stomach,    wherein the pharmaceutical formulation avoids release of ibandronate in the esophagus, and    wherein at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach.    
     
     
         22 . The method of  claim 21 , wherein the bone disease is related to a disorder in calcium metabolism.  
     
     
         23 . The method of  claim 21 , wherein the bone disease is selected from the group consisting of hypercalcemia, osteoporosis, tumor osteolysis and Paget's disease.  
     
     
         24 . The method of  claim 21 , wherein at least 75% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach.  
     
     
         25 . The method of  claim 21 , wherein at least 85% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach.  
     
     
         26 . The method of  claim 21 , wherein at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 2 hours after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         27 . The method of  claim 21 , wherein at least 75% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 2 hours after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         28 . The method of  claim 21 , wherein at least 85% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 2 hours after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         29 . The method of  claim 21 , wherein at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 1 hour after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         30 . The method of  claim 21 , wherein at least 75% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 1 hour after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         31 . The method of  claim 21 , wherein at least 85% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach in less than 1 hour after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         32 . The method of  claim 21 , wherein at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach 1-30 minutes after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         33 . The method of  claim 21 , wherein at least 75% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach 1-30 minutes after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         34 . The method of  claim 21 , wherein at least 85% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach 1-30 minutes after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         35 . The method of  claim 21 , wherein about 80-90% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach within 15 minutes after the pharmaceutical formulation contacts the digestive solution in the patient's stomach.  
     
     
         36 . The method of  claim 21 , wherein the coating comprises at least one member selected from the group consisting of cellulose, cellulose derivatives, dextrins, starches, starch derivatives, carbohydrate polymers, natural gums, polyacrylic acid, polyvinyl alcohol, polyvinyl acetate, polyvinylpyrrolidone, polymethacrylates, polymethacrylate derivates, chitosan, chitosan derivates, shellac, shellac derivates, fats and waxes.  
     
     
         37 . The method of  claim 21 , wherein the coating comprises at least one cellulose derivative selected from the group consisting of methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, sodium carboxymethylcellulose and ethylcellulose.  
     
     
         38 . The method of  claim 21 , wherein the coating comprises at least one polymethacrylate derivative selected from the group consisting of a cationic copolymer of dimethylaminoethyl methacrylate with neutral methacrylic esters, a copolymer of acrylic and methacrylic esters and a copolymer of ethyl acrylate and methyl methacrylate.  
     
     
         39 . The method of  claim 21 , wherein the coating comprises at least one member selected from the group consisting of an anionic copolymer of methacrylic acid and methyl methacrylate, cellulose acetate phthalate, cellulose acetate trimelliatate, methylhydroxypropylcellulose phthalate and polyvinyl acetate phthalate.  
     
     
         40 . In a method of treating bone disease in a patient in need thereof, wherein said method comprises orally administering to a patient a pharmaceutical formulation containing ibandronate, the improvement comprising (a) a core containing a bone disease treating effective amount of ibandronate and (b) a coating which is free of ibandronate surrounding the core, wherein the coating dissolves or is separated from the core during contact with digestive solution in the patient's stomach, and wherein the coating prevents irritation and ulcerations of the esophagus, and wherein at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach.  
     
     
         41 . A method of treating a bone disease in a patient in need thereof, comprising orally administering to the patient a pharmaceutical formulation comprising (a) a core containing a bone disease treating effective amount of ibandronate and (b) a coating which is free of ibandronate, wherein the thickness and type of the coating is chosen so that when the pharmaceutical formulation is administered orally to the patient, the r lease of the ibandronate in the esophagus is avoided, the coating dissolves or is separated from the core during contact with digestive solution in the patient's stomach, and at least 30% of the administered amount of ibandronate is released from the pharmaceutical formulation into the stomach.