Ready to use liquid RECK formulation

1. A ready-to-use liquid formulation comprising:

ropivacaine hydrochloride in an amount of about 2.5 mg/mL;

epinephrine hydrochloride in an amount of about 5 mcg/mL, based on epinephrine free base;

clonidine hydrochloride in an amount of about 0.8 mcg/mL;

ketorolac tromethamine in an amount of about 0.3 mg/mL;

sodium chloride in an amount of about 8.5 mg/mL;

sodium metabisulfite in an amount of about 2.6 mcg/mL;

EDTA sodium in an amount of about 0.2 mg/mL;

optionally citric acid in an amount of about 2 mg/mL;

a sufficient amount of sterile water for injection; and

a sufficient amount of a pH adjuster to obtain a pH of from about 4.6 to about 4.9.

2. The ready-to-use liquid formulation of claim 1 , wherein citric acid is present in the formulation in an amount of about 2 mg/mL.

3. The ready-to-use liquid formulation of claim 1 , wherein the pH is about 4.7 to about 4.8.

4. The ready-to-use liquid formulation of claim 1 , wherein the pH adjuster is hydrochloric acid, sodium hydroxide, or a combination thereof.

5. A syringe comprising about 50 mL of the ready-to-use liquid formulation of claim 1 .

6. The syringe of claim 5 , wherein each of ropivacaine, epinephrine, clonidine, and ketorolac has a potency of at least 90% after storage for about 90 days at a temperature of about 25° C.

7. A light-sensitive container comprising the syringe of claim 5 , wherein the light-sensitive container has a light transmission of less than 5% at any wavelength between 290 nm and 450 nm.

8. A ready-to-use liquid formulation consisting of:

ropivacaine hydrochloride in an amount of about 2.5 mg/mL;

epinephrine hydrochloride in an amount of about 5 mcg/mL, based on epinephrine free base;

clonidine hydrochloride in an amount of about 0.8 mcg/mL;

ketorolac tromethamine in an amount of about 0.3 mg/mL;

sodium chloride in an amount of about 8.5 mg/mL;

sodium metabisulfite in an amount of about 2 mcg/mL to about 10 mcg/mL;

EDTA sodium in an amount of about 0.2 mg/mL;

optionally citric acid in an amount of about 2 mg/mL;

a sufficient amount of sterile water for injection; and

a sufficient amount of a pH adjuster to obtain a pH of from about 4.6 to about 4.9.

9. The ready-to-use liquid formulation of claim 8 , wherein citric acid is present in the formulation in an amount of about 2 mg/mL.

10. The ready-to-use liquid formulation of claim 8 , wherein the pH is about 4.7 to about 4.8.

11. The ready-to-use liquid formulation of claim 8 , wherein the pH adjuster is hydrochloric acid, sodium hydroxide, or a combination thereof.

12. A syringe comprising about 50 mL of the ready-to-use liquid formulation of claim 8 .

13. The syringe of claim 12 , wherein each of ropivacaine, epinephrine, clonidine, and ketorolac has a potency of at least 90% after storage for about 90 days at a temperature of about 25° C.

14. A light-sensitive container comprising the syringe of claim 12 , wherein the light-sensitive container has a light transmission of less than 5% at any wavelength between 290 nm and 450 nm.

15. A method for alleviating post-operative pain in a patient in need thereof, which comprises:

administering the ready-to-use liquid formulation of claim 1 to the patient.

16. A process for preparing the ready-to-use liquid formulation of claim 1 , which comprises:

a) adding sodium metabisulfite and EDTA Sodium in a first container including sterile water for injection and stirring to provide a dissolved solution;

b) adding 10% v/v hydrochloric acid to the first container of step a) to obtain a pH of about 2.5;

c) dissolving epinephrine free base to the first container of step b);

d) optionally, adding 10% v/v hydrochloric acid to the first container of step c) to maintain the pH of the solution below 3.0;

e) adding an additional amount of sterile water to the first container of step d) and adding the pH adjuster to obtain a pH of from about 4.0 to obtain an epinephrine solution;

f) dissolving sodium chloride and ropivacaine hydrochloride in a vessel containing sterile water for injection;

g) adding the pH adjuster to the vessel of step f) to obtain a pH that ranges from about 4.6 to about 4.9;

h) adding separately clonidine hydrochloride, ketorolac tromethamine, and the epinephrine solution of step e) to the vessel;

i) adding an additional amount of sterile water to the vessel of step h) and adding the pH adjuster to obtain a pH that ranges from about 4.6 to about 4.9;

j) transferring the solution of step i) to a second container; and

k) filtering the solution of step j) through a 0.22-micron filter.

17. A syringe comprising about 50 mL of the ready-to-use liquid formulation prepared by the process of claim 16 .

18. The syringe of claim 17 , wherein each of ropivacaine, epinephrine, clonidine, and ketorolac has a potency of at least 90% after storage for about 90 days at a temperature of about 25° C.

19. A light-sensitive container comprising the syringe of claim 17 , wherein the light-sensitive container has a light transmission of less than 5% at any wavelength between 290 nm and 450 nm.