Tazobactam Arginine Compositions
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.