Stabilizing ceftolozane

Abstract

Pharmaceutical compositions can include an amount of a ceftolozane and a stabilizing agent in a formulation for parenteral administration.

1 . A pharmaceutical composition comprising stabilized ceftolozane obtained by a process comprising lyophilizing a composition including ceftolozane and a stabilizing agent selected from the group consisting of: sodium chloride, sucrose, and trehalose, to obtain a lyophilized stabilized ceftolozane pharmaceutical composition, wherein the stabilized ceftolozane is characterized by a reduction in purity of less than 5% at 60 degrees C. over 7 days in a sealed container, as determined by a Develosil column ODS-UG-5; 5 micrometers; 250×4.6 mm, a mobile phase of sodium perchlorate buffer solution (pH 2.5)/CH 3 CN 90:10 (v/v) at a 1.0 mL/min flow rate and oven temperature of 45° C. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the lyophilized stabilized ceftolozane pharmaceutical composition after 3 days at 70 degrees C. after lyophilization comprises at least about 70% of an initial amount of ceftolozane after lyophilization. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the lyophilized stabilized ceftolozane pharmaceutical composition contains 1,000 mg of ceftolozane active. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the stabilizing agent is selected from the group consisting of sucrose and trehalose. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the stabilized ceftolozane is obtained by a process comprising lyophilizing a solution comprising ceftolozane, L-arginine and the stabilizing agent. 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein the stabilized ceftolozane comprises is obtained by a process comprising lyophilizing a composition comprising about 1,000 mg of ceftolozane. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the stabilized ceftolozane is obtained by a process comprising lyophilizing a composition comprising about 300-500 mg of the stabilizing agent. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the stabilizing agent comprises sucrose and trehalose. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the stabilized ceftolozane is obtained by a process comprising lyophilizing a solution comprising ceftolozane, citric acid, L-arginine and about 100-500 mg of the stabilizing agent. 
     
     
         10 . A pharmaceutical composition comprising stabilized ceftolozane and about 300 mg of a stabilizing agent, wherein the stabilizing agent is selected from the group consisting of sucrose and trehalose. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the stabilizing agent comprises trehalose and sucrose. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the stabilizing agent further comprises sodium chloride. 
     
     
         13 . The pharmaceutical composition of  claim 10 , further comprising L-arginine and citric acid. 
     
     
         14 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition comprises 1,000 mg ceftolozane active per unit dose. 
     
     
         15 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition comprises about 300 mg of the stabilizing agent per 1,000 mg of the ceftolozane active. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein
 a. the stabilizing agent further comprises sodium chloride;   b. the pharmaceutical composition comprises 1,000 mg ceftolozane active per unit dose; and   c. the pharmaceutical composition further comprises about 500-700 mg L-arginine per 1,000 mg of ceftolozane active.   
     
     
         17 . A unit dosage form container enclosing a pharmaceutical composition formulated for parenteral administration for the treatment of complicated intra-abdominal infections or complicated urinary tract infections, the pharmaceutical composition comprising 1,000 mg of ceftolozane active, L-arginine, citric acid and about 300-500 mg of a stabilizing agent selected from the group consisting of: sodium chloride, trehalose, and sucrose, wherein the pharmaceutical composition after 7 days at 60 degrees C. wherein the reduction in the purity of ceftolozane active in the pharmaceutical composition is not more than 5% less than the initial amount. 
     
     
         18 . The container of  claim 17  containing 300 mg of a stabilizing agent selected from the group consisting of trehalose and sucrose. 
     
     
         19 . The container of  claim 17 , wherein the pharmaceutical composition is obtained by lyophilizing an aqueous solution comprising about 300-500 mg of the stabilizing agent, an amount of ceftolozane sulfate containing 1,000 mg of ceftolozane active, citric acid, and L-arginine to obtain the pharmaceutical composition as a lyophilized composition. 
     
     
         20 . The container of  claim 19 , further comprising tazobactam sodium.