Formulations of vancomycin

Abstract

Vancomycin-containing compositions substantially free of precipitation after at least about 12 months of storage at refrigerated or ambient conditions are disclosed. The compositions include vancomycin or a pharmaceutically acceptable salt thereof; a polar solvent including propylene glycol, polyethylene glycol and mixtures thereof; lactic acid, a lactate salt, or mixtures thereof; and optionally, a pH adjuster in an amount sufficient to maintain a pH of the compositions at from about 3 to about 8.

We claim: 
     
         1 . A vancomycin-containing composition, comprising:
 a) about 25 mg/mL to about 150 mg/mL vancomycin or a pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable fluid having a pH of about 3 to about 8, comprising:
 i) about 25% (v/v) to about 50% (v/v) of a polar solvent comprising propylene glycol, polyethylene glycol or mixtures thereof; and 
 ii) about 0.25 mmole to about 0.94 mmole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid; 
   wherein the vancomycin-containing composition has less than about 6% degradation of vancomycin B, as determined by HPLC at a wavelength of 280nm, after at least about 12 months of storage at a temperature of from about 5° C. to about 25° C.   
     
     
         2 . The vancomycin-containing composition of  claim 1 , wherein the pH of said vancomycin-containing composition is from about 4 to about 6. 
     
     
         3 . The vancomycin-containing composition of  claim 1 , wherein the pH of said vancomycin-containing composition is about 5.5. 
     
     
         4 . The vancomycin-containing composition of  claim 1 , further comprising a pH adjustor. 
     
     
         5 . The vancomycin-containing composition of  claim 4 , wherein the pH adjustor is a base or conjugate of an acid. 
     
     
         6 . The vancomycin-containing composition of  claim 5 , wherein the base comprises either an amine buffer, sodium hydroxide, calcium hydroxide, or mixtures thereof. 
     
     
         7 . The vancomycin-containing composition of  claim 5 , wherein the base is sodium hydroxide. 
     
     
         8 . The vancomycin-containing composition of  claim 4 , wherein the pH adjustor is an acid. 
     
     
         9 . The vancomycin-containing composition of  claim 8 , wherein the acid comprises either acetic acid, citric acid, hydrochloric acid, phosphoric acid, malic acid, or mixtures thereof. 
     
     
         10 . The vancomycin-containing composition of  claim 9 , wherein the acid comprises hydrochloric acid. 
     
     
         11 . The vancomycin-containing composition of  claim 1 , wherein the pharmaceutically acceptable fluid comprises about 0.75 mmole to about 1 mole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid. 
     
     
         12 . The vancomycin-containing composition of  claim 1 , wherein the pharmaceutically acceptable fluid comprises about 0.75 mmole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid. 
     
     
         13 . The vancomycin-containing composition of  claim 1 , wherein the pharmaceutically acceptable fluid comprises about 1 mole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid. 
     
     
         14 . The vancomycin-containing composition of  claim 1 , wherein the polar solvent is propylene glycol. 
     
     
         15 . The vancomycin-containing composition of  claim 14 , wherein the pharmaceutically acceptable fluid comprises about 0.25 to about 0.625 mmole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid and about 50% (v/v) propylene glycol. 
     
     
         16 . The vancomycin-containing composition of  claim 14 , wherein the pharmaceutically acceptable fluid comprises about 0.3 mmole to about 1.0 mole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid and about 25% (v/v) propylene glycol. 
     
     
         17 . The vancomycin-containing composition of  claim 1 , wherein the polar solvent is polyethylene glycol. 
     
     
         18 . The vancomycin-containing composition of  claim 17 , wherein the pharmaceutically acceptable fluid comprises about 0.25mmole to about 0.62 mmole of lactic acid, lactate or mixtures thereof per mL of pharmaceutically acceptable fluid and about 50% (v/v) polyethylene glycol. 
     
     
         19 . The vancomycin-containing composition of  claim 1 , wherein the composition is substantially free of precipitation after at least about 12 months of storage at a temperature of from about 5° C. to about 25° C. 
     
     
         20 . The vancomycin-containing composition of  claim 1 , wherein the amount of vancomycin is from about 75 mg/mL to about 100 mg/mL.