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 method of administering ephedrine to a subject having hypotension or at risk of developing hypotension in need thereof, the method comprising:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration, and
a bacterial endotoxin level not more than 7 EU/mg; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
2. The method of claim 1 , wherein the method consists essentially of the steps of:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration, and
a bacterial endotoxin level not more than 7 EU/mg; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
3. The method of claim 1 , wherein the method further comprises, before the step of removing:
combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution comprising an initial ephedrine sulfate level of 5 mg/mL, 9 mg/mL sodium chloride or 5% dextrose, and no preservative;
optionally contacting the batch solution with an acid or a base to obtain an initial pH level of the solution of 4.5 to 7;
filtering the batch solution through a membrane filter to obtain a filtered batch solution;
placing not more than 20 mL of the filtered batch solution into the syringe to obtain one or more filled syringes; and
sealing each of the one or more filled syringes in the packaging.
4. A method of administering ephedrine to a subject having hypotension or at risk of developing hypotension in need thereof, the method comprising:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration, and
a level of (+)-1 S,2R-ephedrine not more than 0.5%; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
5. The method of claim 4 , wherein the method consists essentially of the steps of:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration, and
a level of (+)-1 S,2R-ephedrine not more than 0.5%; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
6. The method of claim 4 , wherein the method further comprises, before the step of removing:
combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution comprising an initial ephedrine sulfate level of 5 mg/mL, 9 mg/mL sodium chloride or 5% dextrose, and no preservative;
optionally contacting the batch solution with an acid or a base to obtain an initial pH level of the solution of 4.5 to 7;
filtering the batch solution through a membrane filter to obtain a filtered batch solution;
placing not more than 20 mL of the filtered batch solution into the syringe to obtain one or more filled syringes; and
sealing each of the one or more filled syringes in the packaging.
7. A method of administering ephedrine to a subject having hypotension or at risk of developing hypotension in need thereof, the method comprising:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration, and
a pH level within 0.5 pH units of the initial pH level; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
8. The method of claim 7 , wherein the method consists essentially of the steps of:
removing, from sealed packaging, a 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 or 5% dextrose,
no preservative,
water,
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 at least 95% of the packaged concentration; and
injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition.
9. The method of claim 7 , wherein the method further comprises, before the step of removing:
combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution comprising an initial ephedrine sulfate level of 5 mg/mL, 9 mg/mL sodium chloride or 5% dextrose, and no preservative;
optionally contacting the batch solution with an acid or a base to obtain an initial pH level of the solution of 4.5 to 7;
filtering the batch solution through a membrane filter to obtain a filtered batch solution;
placing not more than 20 mL of the filtered batch solution into the syringe to obtain one or more filled syringes; and
sealing each of the one or more filled syringes in the packaging.