Compositions comprising ephedrine or an ephedrine salt and methods of making and using same
The present disclosure provides compositions comprising ephedrine sulfate ready for immediate use in a clinical setting, and methods of making and using same.
1. A pharmaceutical product comprising:
a packaged syringe containing a sterilized ready-to-use ephedrine composition comprising:
a packaged concentration of ephedrine sulfate of 5 mg/mL,
9 mg/mL sodium chloride,
no preservative,
water, and
an initial pH level of about 4.5 to about 7; and
having, after storage in the syringe at 25° C. and 60% relative humidity for 12 months or after storage at 40° C. and 75% relative humidity for 6 months:
a pH level within 0.5 pH units of the initial pH level,
an ephedrine sulfate concentration of at least 95% of the packaged concentration, and
a bacterial endotoxin level not more than 7 EU/mg.
2. The pharmaceutical product of claim 1 , wherein the ready-to-use packaged pharmaceutical product is prepared by a process comprising:
mixing the ephedrine sulfate with the sodium chloride, no preservative, and water to form an ephedrine sulfate composition;
inserting the ephedrine sulfate composition into the syringe; and
terminally sterilizing the ephedrine sulfate composition in the syringe.
3. The pharmaceutical product of claim 2 , wherein the step of terminally sterilizing comprises sealing the syringe and heating the sealed syringe at about 122° C. for about 15 minutes.
4. The pharmaceutical product of claim 2 , wherein the process further comprises filtering the ephedrine sulfate composition before inserting the ephedrine sulfate composition into the syringe.
5. A pharmaceutical product comprising:
a packaged syringe containing a shelf-stable sterilized ephedrine composition comprising:
a packaged concentration of ephedrine sulfate of 5 mg/mL;
9 mg/mL sodium chloride;
water;
no preservative;
an initial pH level of about 4.5 to about 7; and
having, after storage in the syringe at 25° C. and 60% relative humidity for 12 months or after storage at 40° C. and 75% relative humidity for 6 months:
an ephedrine sulfate concentration of at least 95% of the packaged concentration, and
a level of (+)-1S,2R-ephedrine not more than 0.5%.
6. The pharmaceutical product of claim 5 , wherein the shelf-stable sterilized ephedrine composition is sterilized by terminally sterilizing the ephedrine composition in the syringe.
7. The pharmaceutical product of claim 6 , wherein the step of terminally sterilizing comprises sealing the syringe and heating the sealed syringe at about 122° C. for about 15 minutes.
8. The pharmaceutical product of claim 5 , wherein the shelf-stable sterilized ephedrine composition has a pH level within 0.5 pH units of the initial pH level after storage at 25° C. and 60% relative humidity for 12 months.
9. The pharmaceutical product of claim 5 , wherein the shelf-stable sterilized ephedrine composition has a pH level within 0.5 pH units of the initial pH level after storage at 40° C. and 75% relative humidity for 6 months.
10. A pharmaceutical product comprising:
a packaged ready-to-use single-use container comprising a shelf-stable sterilized pharmaceutical composition comprising:
a packaged concentration of ephedrine sulfate of 5 mg/mL;
9 mg/mL sodium chloride;
water;
no preservative;
an initial pH level of about 4.5 to about 7; and
having, after storage in the single-use container at 25° C. and 60% relative humidity for 12 months or after storage at 40° C. and 75% relative humidity for 6 months:
an ephedrine sulfate concentration of at least 95% of the packaged concentration, and
a pH level within 0.5 pH units of an initial pH level.
11. The pharmaceutical product of claim 10 , wherein the single-use container is a syringe.
12. The pharmaceutical product of claim 10 , wherein the pharmaceutical composition is sterilized by terminally sterilizing the pharmaceutical composition in the single-use container.
13. The pharmaceutical product of claim 12 , wherein the step of terminally sterilizing comprises sealing the single-use container and heating the sealed single-use container at about 122° C. for about 15 minutes.
14. The pharmaceutical product of claim 10 , wherein the pharmaceutical product has a pH level within 0.5 pH units of the initial pH level after storage at 25° C. and 60% relative humidity for 12 months.
15. The pharmaceutical product of claim 10 , wherein the pharmaceutical product has a pH level within 0.5 pH units of the initial pH level after storage at 40° C. and 75% relative humidity for 6 months.
16. The pharmaceutical product of claim 10 , wherein the shelf-stable sterilized pharmaceutical composition has, after storage at 25° C. and 60% relative humidity for 12 months or after storage at 40° C. and 75% relative humidity for 6 months, a particulate matter level of not more than 6,000 particles having a size greater than or equal to 10 μm.