Stable pharmaceutical compositions of succinylcholine chloride

Abstract

The present invention relates to injectable pharmaceutical compositions comprising therapeutically effective amount of succinylcholine chloride, one or more pharmaceutically acceptable aqueous solvents, and one or more stabilizing agents selected from aliphatic polyols; lower alkyl alcohols; amino acids having at least one additional amino, carboxyl or hydroxyl group; amino alcohols; and aliphatic dicarboxylic acids having at least one hydroxyl or amino group, or α-β unsaturation. The compositions are stable at room temperature for at least 30 days. Methods of manufacturing the injectable pharmaceutical compositions are also provided. The composition may be provided in a sealed container, e.g., an ampoule, vial and pre-filled syringe, and are suitable for subcutaneous, intravenous or intramuscular administration as an adjunct to general anesthesia, to facilitate tracheal intubation, and/or to provide skeletal muscle relaxation during surgery or mechanical ventilation.

1 . An injectable pharmaceutical composition comprising;
 (i) therapeutically effective amount of succinylcholine chloride;   (ii) one or more stabilizing agents;   (iii) one or more pharmaceutically acceptable solvents,   wherein the composition is stable at room temperature for at least 30 days,   wherein water is at least one of the pharmaceutically acceptable solvents, and   wherein the stabilizing agents are selected from the group consisting of aliphatic polyols; lower alkyl alcohols; amino acids having at least one additional amino, carboxyl or hydroxyl group; amino alcohols; and aliphatic dicarboxylic acids having at least one hydroxyl or amino group, or α-β unsaturation.   
     
     
         2 . The composition of  claim 1 , wherein the composition is free of tonicity contributing agent. 
     
     
         3 . The composition of  claim 1 , wherein the composition is disposed in a pre-filled syringe or vial. 
     
     
         4 . The composition of  claim 1 , wherein succinylcholine chloride is present at concentration of about 5 mg/mL to about 60 mg/mL. 
     
     
         5 . The composition of  claim 1 , wherein the stabilizing agent is selected from propylene glycol, polyethylene glycol, glycerol, cyclodextrin, cyclodextrin derivatives, ethanol, glutamic acid, aspartic acid, arginine, lysine, meglumine, diethanolamine, tromethamine, maleic acid, tartaric acid, and mixtures thereof. 
     
     
         6 . The composition of  claim 1 , wherein the composition has total impurities of less than about 6.0% (w/w) as measured by HPLC, when stored at 25° C./40% RH for up to 90 days. 
     
     
         7 . The composition of  claim 1 , wherein the composition has succinic acid impurity of less than about 0.5% (w/w) as measured by HPLC, when stored at 25° C./40% RH for up to 90 days. 
     
     
         8 . The composition of  claim 1 , wherein the composition has succinylmonocholine impurity of less than about 5.0% (w/w) as measured by HPLC, when stored at 25° C./40% RH for up to 90 days. 
     
     
         9 . The composition of  claim 1 , wherein the composition has choline impurity of less than about 3.0% (w/w) as measured by HPLC, when stored at 25° C./40% RH for up to 90 days. 
     
     
         10 . The composition of  claim 1 , wherein the composition has a pH in the range of from about 3 to about 5. 
     
     
         11 . The pharmaceutical composition according to  claim 3 , wherein the pre-filled syringe is made up of a polymeric materials selected from the group consisting of polysulfone, polycarbonate, polypropylene, polyethylene, ethylene/propylene copolymers, polyolefins, acrylic-imide copolymers, polyester, poly (1,1,2,2 tetrafluoroethylene), Nylon, polyoxymethylene, polymethylpentene, polyvinylidene chloride, ethylvinylacetate, cyclic olefin polymer, cyclic olefin copolymer, crystal zenith, and mixtures thereof. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the composition is sterilized using a technique selected from the group consisting of filtration through aseptic filtration-filling-sealing process, terminal sterilization, incorporation of sterilizing agents, irradiation, and heating. 
     
     
         13 . A kit comprising the composition of  claim 1 , wherein the kit further comprises an injection device for administration of the composition to a subject in need of such pharmaceutical composition. 
     
     
         14 . The kit of  claim 13 , wherein the injection device comprises a needle and prefilled syringe or syringe cartridge with the composition disposed therein. 
     
     
         15 . The composition of  claim 1 , wherein the aliphatic polyols and/or lower alkyl alcohols are present at a concentration of less than about 300 mg/mL. 
     
     
         16 . The composition of  claim 15 , wherein the concentration is from about 20 mg/mL to about 300 mg/mL. 
     
     
         17 . The composition of  claim 1 , wherein the amino acids having at least one additional amino, carboxyl or hydroxyl group; amino alcohols; and/or aliphatic dicarboxylic acids having at least one hydroxyl or amino group, or α-β unsaturation are present at a concentration of less than about 2 mg/mL. 
     
     
         18 . The composition of  claim 18 , wherein the concentration is from about 0.1 mg/mL to about 2 mg/mL. 
     
     
         19 . An injectable pharmaceutical composition comprising;
 (i) succinylcholine chloride at a concentration of about 20 mg/mL,   (ii) propylene glycol,   (iii) purified water,   wherein the composition is free of sodium chloride,   wherein the composition is disposed in a pre-filled syringe and is stable at room temperature for at least 30 days.   
     
     
         20 . The composition of  claim 1 , wherein succinylcholine chloride is present at a concentration of 20 mg/mL. 
     
     
         21 . A method of providing succinylcholine as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation to a human subject in need thereof comprising administration of the subject the injectable pharmaceutical compositions of  claim 1 .