Injectable liquid paracetamol formulation
The invention relates to an aqueous paracetamol solution for its use by perfusion with a pH between 4.5 and 6.0, comprising at least one substance that can react with phenolates giving rise to its O-derivatives or other coordination compounds. The injectable paracetamol solution of the present invention has high stability, does not develop color over time and has a minimal content of impurities.
1. A method of preparing a stable aqueous perfusion paracetamol solution for injection having a pH of 5.0, that contains impurities no more than or equal to 0.13% resulting from paracetamol degradation after heat sterilization when tested by storing in a plastic container for at least 89 hours at 70° C., the method consisting of:
a) incorporating into a paracetamol solution glucose at a concentration between 0.5% m/v to 3.0% m/v to stabilize said solution, to which is further added a chelant and a buffering agent;
b) placing the paracetamol solution of step a into a plastic container; and
c) sterilizing the paracetamol solution in the plastic container by heat;
wherein the stable aqueous perfusion paracetamol solution for injection is prepared without the removal of oxygen; and
wherein the stable aqueous perfusion paracetamol solution contains impurities no more than or equal to 0.13% resulting from paracetamol degradation after heat sterilization when tested by storing in the plastic container for at least 89 hours at 70° C., and wherein the solution is suitable for injection.
2. The method of claim 1 wherein buffering agent is selected from the group consisting of: citrates, malates, acetates, lactates, and gluconates.
3. The method of claim 1 wherein the buffering agent is sodium acetate and/or sodium citrate.
4. The stable aqueous perfusion paracetamol solution prepared by the method of claim 1 .
5. A method of preparing a stable aqueous perfusion paracetamol solution for injection having a pH of 5.0, that contains impurities no more than or equal to 0.13% resulting from paracetamol degradation after sterilization when tested by storing in a plastic container for at least 89 hours at 70° C., the method consisting of:
a) incorporating into a paracetamol solution glucose at a concentration between 0.5% m/v and 3.0% m/v to stabilize said solution, to which is further added a chelant and a buffering agent;
b) sterilizing the paracetamol solution by filtration;
c) placing the paracetamol solution of step b into a plastic container; and
wherein the stable aqueous perfusion paracetamol solution for injection is prepared without the removal of oxygen; and
wherein the stable aqueous perfusion paracetamol solution contains impurities no more than or equal to 0.13% resulting from paracetamol degradation after sterilization when tested by storing in the plastic container for at least 89 hours at 70° C., and wherein the solution is suitable for injection.
6. The method of claim 5 wherein the sterilization further involves heat sterilization.
7. The method of claim 5 wherein the buffering agent is sodium acetate and/or sodium citrate.