Tazobactam Arginine Compositions

Abstract

This disclosure provides compositions containing solid forms of tazobactam arginine, and methods of manufacturing and using these compositions.

1 - 6 . (canceled) 
     
     
         7 . A composition obtained by a process comprising the steps of:
 a) combining L-arginine, tazobactam acid and acetone in an aqueous solution at a pH of 5.9+/−0.5;   b) allowing a solid tazobactam arginine composition to precipitate from the aqueous solution; and   c) obtaining the solid tazobactam arginine composition from the aqueous solution.   
     
     
         8 . The composition of  claim 7 , wherein the tazobactam acid and L-arginine are combined in the aqueous solution before combination with the acetone. 
     
     
         9 . The composition of  claim 8 , wherein the aqueous solution is at a temperature of about 22-30 degrees C. 
     
     
         10 . The composition of  claim 9 , further comprising cooling the solution comprising L-arginine, tazobactam acid and acetone to a temperature of about 10-15 degrees C. prior to obtaining the solid tazobactam arginine composition from the aqueous solution. 
     
     
         11 . The composition of  claim 7 , further comprising combining the solid tazobactam arginine composition with a beta lactam antibiotic in a pharmaceutical composition. 
     
     
         12 . The composition of  claim 7 , wherein the solid tazobactam arginine composition has a differential scanning calorimetry (DSC) thermogram having a characteristic peak at about 209 degrees C. 
     
     
         13 . The composition of  claim 7 , wherein the solid tazobactam arginine composition has a thermogravity (TG) curve with an onset temperature of about 201 degrees C. 
     
     
         14 . The composition of  claim 7 , wherein the solid tazobactam arginine composition has a solubility in acetic acid of greater than about 100 mg/mL at about 22 degrees C. 
     
     
         15 . The composition of  claim 7 , wherein the solid tazobactam arginine composition has a solubility in water of greater than about 100 mg/mL at about 22 degrees C. 
     
     
         16 . The composition of  claim 8 , obtained by a method further comprising cooling the solution comprising L-arginine, tazobactam acid and acetone to a temperature of about 10-15 degrees C. prior to obtaining the solid tazobactam arginine composition from the aqueous solution, and combining the solid tazobactam arginine composition with a beta lactam antibiotic selected from the group consisting of the compounds in Table 2 in a pharmaceutical composition, wherein:
 a) the aqueous solution is at a temperature of about 22-30 degrees C.;   b) the solid tazobactam arginine composition has a differential scanning calorimetry (DSC) thermogram having a characteristic peak at about 209 degrees C.; and   c) the solid tazobactam arginine composition has a thermogravity (TG) curve with an onset temperature of about 201 degrees C.   
     
     
         17 . A composition obtained by a method comprising the steps of:
 a) combining L-arginine, tazobactam acid and isopropanol in an aqueous solution;   b) allowing a solid tazobactam arginine composition to precipitate from the aqueous solution; and   c) obtaining the solid tazobactam arginine composition from the aqueous solution.   
     
     
         18 . The composition of  claim 17 , wherein the tazobactam acid and L-arginine are combined in the aqueous solution before combination with the isopropanol. 
     
     
         19 . The composition of  claim 18 , wherein the aqueous solution is at a temperature of about 22-30 degrees C. 
     
     
         20 . The composition of  claim 19 , further comprising combining the solid tazobactam arginine composition with a beta lactam antibiotic in a pharmaceutical composition. 
     
     
         21 . The composition of  claim 20 , wherein the beta lactam antibiotic is selected from the group consisting of the beta lactam compounds of Table 2. 
     
     
         22 . The composition of  claim 17 , wherein the solid tazobactam arginine composition has a differential scanning calorimetry (DSC) thermogram having a characteristic peak at about 209 degrees C. 
     
     
         23 . The composition of  claim 17 , wherein the solid tazobactam arginine composition has a thermogravity (TG) curve with an onset temperature of about 201 degrees C. 
     
     
         24 . The composition of  claim 17 , wherein the solid tazobactam arginine composition has a solubility in acetic acid of greater than about 100 mg/mL at about 22 degrees C. 
     
     
         25 . The composition of  claim 17 , wherein the solid tazobactam arginine composition has a solubility in water of greater than about 100 mg/mL at about 22 degrees C. 
     
     
         26 . The composition of  claim 18 , obtained by a method further comprising cooling the solution comprising L-arginine, tazobactam acid and isopropanol to a temperature of about 10 degrees C. prior to obtaining the solid tazobactam arginine composition from the aqueous solution, and combining the solid tazobactam arginine composition with a beta lactam antibiotic selected from the group consisting of the compounds in Table 2 in a pharmaceutical composition, wherein:
 a) the aqueous solution is at a temperature of about 25 degrees C.;   b) the solid tazobactam arginine composition has a differential scanning calorimetry (DSC) thermogram having a characteristic peak at about 209 degrees C.; and   c) the solid tazobactam arginine composition has a thermogravity (TG) curve with an onset temperature of about 201 degrees C.   
     
     
         27 . A pharmaceutical composition obtained by a process comprising the steps of:
 a) combining tazobactam, L-arginine in an aqueous solution with an antisolvent selected from the group consisting of acetone and isopropanol;   b) allowing a solid composition comprising tazobactam and L-arginine to precipitate from the aqueous solution;   c) obtaining the solid composition from the aqueous solution and   d) combining the solid composition with a beta lactam antibiotic in a pharmaceutical composition comprising tazobactam and L-arginine.