Storage stable thyroxine active drug formulations and methods for their production

Abstract

This invention provides a storage-stable dosage form of a thyroxine active drug composition which exhibits an improved stability. The formulation contains a thyroxine active drug substance, an alditol, and a saccharide, and, optionally, additional pharmaceutically accepted excipients. Levothyroxine sodium is the preferred active drug substance, mannitol is the preferred alditol, and sucrose is the9 preferred saccharide. Additional preferred excipients include, for example, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and sodium lauryl sulfate.

1 . A storage stable pharmaceutical composition which comprises a therapeutically effective amount of a thyroxine active drug, a stabilizing amount of an alditol, a stabilizing amount of a saccharide, and optionally further comprises other pharmaceutically acceptable excipients.  
     
     
         2 . The composition of  claim 1 , wherein said thyroxine active drug is levothyroxine sodium.  
     
     
         3 . The composition of  claim 1 , wherein said alditol is selected from the group consisting of mannitol, sorbitol, maltitol and xylitol.  
     
     
         4 . The composition of  claim 1 , wherein said alditol is mannitol.  
     
     
         5 . The composition of  claim 1 , wherein said saccharide is selected from a reducing sugar, an aldose, a hemiacetal, a cyclic hemiacetal and a cyclized aldose.  
     
     
         6 . The composition of  claim 1 , wherein said saccharide is selected from the group consisting of a monosaccharide, a disaccharide, and an oligosaccharide.  
     
     
         7 . The composition of  claim 1 , wherein said saccharide is selected from the group consisting of sucrose, maltose, cellobiose, lactose, trehalose, glucose, fructose, galactose, ribose and deoxyribose.  
     
     
         8 . The composition of  claim 1 , wherein said saccharide is a disaccharide.  
     
     
         9 . The composition of  claim 8 , wherein said disaccharide is sucrose.  
     
     
         10 . A storage stable pharmaceutical composition which comprises a therapeutically effective amount of a thyroxine active drug, an alditol in the amount of about 5% to about 90% of the total weight of said composition, and a saccharide in an amount of about 5% to about 70% of the total weight of said composition.  
     
     
         11 . The composition of  claim 1 , which comprises at least one further pharmaceutical excipient.  
     
     
         12 . A storage stable oral pharmaceutical composition which comprises a therapeutically effective amount of levothyroxine sodium, a stabilizing amount of mannitol, a stabilizing amount of sucrose, and optionally further comprises other pharmaceutically acceptable excipients.  
     
     
         13 . The composition of  claim 12 , wherein said stabilizing amount of mannitol is from about 5% to about 90% of the total weight of said composition and wherein said stabilizing amount of sucrose is from about 5% to about 70% of the total weight of said composition.  
     
     
         14 . The composition of  claim 12 , wherein said stabilizing amount of mannitol is from about 15% to about 80% of the total weight of said composition and wherein said stabilizing amount of sucrose is from about 10% to about 60% of the total weight of said composition.  
     
     
         15 . A storage stable oral pharmaceutical composition which comprises a therapeutically effective amount of levothyroxine sodium, mannitol in an amount of about 5% to about 90% of the total weight of said composition, sucrose in an amount of about 5% to about 70% of the total weight of said composition, and optionally further comprises microcrystalline cellulose, polyvinylpyrrolidone, crospovidone, magnesium stearate, sodium lauryl sulfate, and colloidal silicon dioxide.  
     
     
         16 . The composition of  claim 1 , which is a solid oral dosage form.  
     
     
         17 . The composition of  claim 1 , which is selected from the group consisting of a tablet, a capsule, a rectal suppository, a vaginal suppository, a pill, a dragee, a lozenge, granules, beads, microspheres, pellets, a powder or any combination thereof.  
     
     
         18 . The composition of  claim 1 , which is a powder.  
     
     
         19 . The composition of  claim 1 , which is a granulate.  
     
     
         20 . The composition of  claim 1 , which is a tablet.  
     
     
         21 . The composition of  claim 1 , which is formulated for oral, rectal, vaginal, transmucosal, transdermal, parental, subcutaneous or intramuscular administration.  
     
     
         22 . A method for the treatment of thyroid disorders comprising orally administering the composition of  claim 1 , to a human.