Crystallization method and bioavailability

Abstract

Preparation, in-vitro and in vivo characterization of novel forms of (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl) phosphonic acid, suitable for pharmaceutical compositions in drug delivery systems for humans.

The claimed invention is: 
     
         1 . A molecular complex comprising zoledronic acid and sodium. 
     
     
         2 . A pharmaceutical composition comprising a molecular complex of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein the composition is an oral dosage form. 
     
     
         4 . A molecular complex of  claim 1 , wherein the molecular complex is crystalline. 
     
     
         5 . A molecular complex of  claim 1  comprising zoledronic acid, sodium zoledronate and water. 
     
     
         6 . A molecular complex of  claim 5 , wherein the molecular complex is crystalline. 
     
     
         7 . A pharmaceutical composition comprising a molecular complex of  claim 4  and a pharmaceutically acceptable excipient. 
     
     
         8 . A pharmaceutical composition according to  claim 7 , wherein the composition is an oral dosage form. 
     
     
         9 . A molecular complex of  claim 5 , wherein the sodium zoledronate is monosodium zoledronate. 
     
     
         10 . A pharmaceutical composition comprising a molecular complex of  claim 9  and a pharmaceutically acceptable excipient. 
     
     
         11 . A molecular complex of  claim 5 , wherein the sodium zoledronate is disodium zoledronate. 
     
     
         12 . A pharmaceutical composition comprising a molecular complex of  claim 11  and a pharmaceutically acceptable excipient. 
     
     
         13 . A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to  claim 1 . 
     
     
         14 . A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to  claim 5 . 
     
     
         15 . A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to  claim 9 . 
     
     
         16 . A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to  claim 11 .