Stable pharmaceutical compositions of succinylcholine chloride
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. A pharmaceutical composition consisting of:
(i) therapeutically effective amount of succinylcholine chloride at a concentration of from about 5 mg/mL to 60 mg/mL;
(ii) propylene glycol as a stabilizing agent at a concentration of from about 20 mg/mL to about 300 mg/mL;
(iii) water as a solvent;
(iv) optionally one or more pH adjusting agents; and
(v) optionally sodium chloride as a tonicity contributing agent at a concentration of from about 1 mg/mL to about 50 mg/mL
wherein the composition is in the form of a ready to use aqueous solution suitable for parenteral administration, and
wherein the aqueous solution has a pH of about 3 to about 5 and is stable at room temperature for at least 30 days.
2. The composition of claim 1 , wherein succinylcholine chloride is present at a concentration of about 20 mg/mL.
3. The composition of claim 1 , wherein the composition is free of tonicity contributing agent.
4. The composition of claim 1 , wherein the composition is disposed in a pre-filled syringe or vial.
5. 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.
6. 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.
7. 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.
8. 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.
9. The pharmaceutical composition according to claim 4 , 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.
10. 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.
11. 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.
12. The kit of claim 11 , wherein the injection device comprises a needle and prefilled syringe or syringe cartridge with the composition disposed therein.
13. A method of providing succinylcholine as an adjunct to general anaesthesia, 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 .