Long term sustained release pharmaceutical composition containing aqueous suspension of bisphosphonate

Abstract

Pharmaceutical compositions for long-term sustained release of bisphosphonate drugs are provided. In one embodiment, the composition includes an aqueous suspension of a solid which includes a salt of a bisphosphonate drug and a salt of pentavalent phosphorus oxoacid. The compositions can be used to treat a variety of bone diseases, including osteoporosis.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising:
 an amorphous sosoloid comprising:
 a salt of a bisphosphonate drug; and 
 a salt of a pentavalent phosphorus oxoacid. 
   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the salt of the bisphosphonate drug is present in an amount of less than about 50% by weight based on the total weight of the amorphous sosoloid. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the bisphosphonate drug comprises a compound represented by (HO) 2 PO—R—OP(OH) 2 , wherein the chemical composition of the functional group R dictates the bisphosphonate drug as pamidronic acid, alendronic acid, ibandronic acid, risedronic acid, zoledronic acid or tiludronic acid. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the salt of the bisphosphonate drug comprises a salt selected from the group consisting of:
 normal salts, acidic salts, basic salts and combinations thereof;   calcium salts, zinc salts, magnesium salts, and combinations thereof; and   anhydrous salts, hydrates and combinations of hydrates.   
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein a weight ratio of metal to phosphorus ranges from about 0.5 to about 3.0. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the salt of the pentavalent phosphorus oxoacid comprises a salt selected from the group consisting of:
 normal salts, acidic salts, basic salts and combinations thereof;   calcium salts, zinc salts, magnesium salts, and combinations thereof;   phosphates, pyrophosphates, metaphosphates, polyphosphates and combinations thereof; and   anhydrous salts, hydrates and combinations of hydrates.   
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the salt of the pentavalent phosphorus oxoacid is selected from the group consisting of dicalcium phosphate dihydrate, dicalcium phosphate anhydrate, octacalcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate, amorphous calcium phosphate, calcium-deficient hydroxyapatite, hydroxyapatite, and tetracalcium phosphate. 
     
     
         8 . The pharmaceutical composition according to  claim 1  wherein, wherein the amorphous sosoloid has an average particle size of less than about 100 micrometers. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the amorphous sosoloid suspended in an aqueous medium to form an aqueous suspension. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the aqueous suspension has a pH ranging from about 6.0 to about 9.5. 
     
     
         11 . The pharmaceutical composition according to  claim 1 , wherein the amorphous sosoloid has a solubility in saline of less than about 0.05% by weight as bisphosphonic acid. 
     
     
         12 . The pharmaceutical composition according to  claim 1 , further comprising at least one inactive pharmaceutical excipient. 
     
     
         13 . The pharmaceutical composition according to  claim 12 , wherein the inactive pharmaceutical excipient is selected from the group consisting of surfactants, suspending agents, dispersing agents, tonicity agents, preservatives, pH buffers, agents for adjusting osmotic pressure, agents for adjusting viscosity and agents for adjusting density. 
     
     
         14 . A pharmaceutical composition comprising an aqueous suspension of an amorphous sosoloid, the amorphous sosoloid comprising:
 a calcium salt of a bisphosphonate drug; and   a calcium salt of a pentavalent phosphorus oxoacid.   
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the calcium salt of the bisphosphonate drug is present in an amount of less than about 50% by weight based on the total weight of the amorphous sosoloid. 
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein the amorphous sosoloid has an average particle size ranging from about 1 to about 100 micrometers. 
     
     
         17 . The pharmaceutical composition according to  claim 14 , wherein the aqueous suspension of the amorphous sosoloid has a pH ranging from about 6.0 to about 9.5. 
     
     
         18 . The pharmaceutical composition according to  claim 14 , wherein a weight ratio of calcium to phosphorus ranges from about 0.5 to about 3.0. 
     
     
         19 . The pharmaceutical composition according to  claim 14 , wherein the amorphous sosoloid has a solubility in saline of less than about 0.05% by weight as bisphosphonic acid.