Infusion bag of Midazolam for intravenous use

Patent metadata

Field	Value
Publication number	US-12102594-B2
Application number	US-202217646861-A
Country	US
Kind code	B2
Filing date	Jan 3, 2022
Priority date	Feb 22, 2019
Publication date	Oct 1, 2024
Grant date	Oct 1, 2024

Abstract

The invention relates to an infusion container comprising a sterile, ready-to-use, stable aqueous solution of Midazolam or a pharmaceutically acceptable salt thereof, suitable for direct intravenous infusion to a patient in need thereof. The invention also relates to a novel infusion container having plurality of ports that is suitable for delivering or receiving a sterile fluid, such as the said stable aqueous solution of Midazolam or a pharmaceutically acceptable salt thereof.

First claim

We claim:

1. A ready-to-use pre-filled syringe comprising a stable, aqueous solution of midazolam, wherein the solution comprises:
a. 0.1 mg/ml to 2.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically salt thereof;
b. a tonicity adjusting agent;
c. a pH adjusting agent; and
d. water for injection,

wherein the syringe was subjected to terminal sterilization by autoclaving, and the solution has a pH of 3.0 to 4.5.

2. The ready-to-use pre-filled syringe according to claim 1 , wherein the solution has a concentration of 2.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically acceptable salt thereof.

3. The ready-to-use pre-filled syringe according to claim 1 , wherein the stable, aqueous solution has a concentration of 1.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically acceptable salt thereof.

4. The ready-to-use pre-filled syringe according to claim 1 , wherein the tonicity adjustment agent comprises sodium chloride.

5. The ready-to-use pre-filled syringe according to claim 1 , wherein the tonicity adjustment agent comprises about 0.9% w/v sodium chloride.

6. The ready-to-use pre-filled syringe according to claim 1 , wherein each ml of the stable aqueous solution comprises 1 mg midazolam and about 0.9% w/v sodium chloride.

7. The ready-to-use pre-filled syringe according to claim 1 , wherein the pH adjusting agent comprises hydrochloric acid, sodium hydroxide, or a combination thereof.

8. The ready-to-use pre-filled syringe according to claim 1 , wherein the pH of the stable, aqueous solution is 3.0 to 4.0.

9. The ready-to-use pre-filled syringe according to claim 1 , wherein the pH of the stable, aqueous solution is 3.3.

10. The ready-to-use pre-filled syringe according to claim 1 , wherein the stable aqueous solution is free of a preservative.

11. The ready-to-use pre-filled syringe according to claim 1 , wherein the stable aqueous solution is free of a chelating agent, an antioxidant, a stabilizer, a complexing agent and a preservative.

12. The ready-to-use pre-filled syringe according to claim 1 , wherein the fill volume is 50 ml.

13. The ready-to-use pre-filled syringe according to claim 1 , wherein the aqueous solution of midazolam of a pharmaceutically acceptable salt thereof in the syringe remains free of any sub-visible particles at room temperature for at least 6 months.

14. The ready-to-use pre-filled syringe according to claim 1 , wherein an innermost layer of the ready-to-use pre-filled syringe comprises a cyclo-olefin polymer or a cyclo-olefin copolymer.

15. The ready-to-use pre-filled syringe according to claim 1 , wherein an innermost layer of the ready-to-use pre-filled syringe comprises a cyclo-olefin polymer.

16. A method of treating a disease or a condition or providing a supportive medication comprising administering to a patient in need thereof by injection, a stable, aqueous solution of midazolam or a pharmaceutically acceptable salt thereof from a ready-to-use pre-filled syringe of claim 1 .

17. The method according to claim 16 , wherein said disease or condition for treatment or for providing supportive medication is selected from the group consisting of preoperative sedation, anxiolysis, amnesia, for induction of general anesthesia, and before administration of other anesthetic agents.

18. The ready-to-use pre-filled syringe according to claim 1 , wherein the syringe was autoclaved at 121° C. for 15 minutes.

19. A ready-to-use pre-filled syringe comprising a stable, aqueous solution of midazolam, wherein the solution comprises:
a. 0.1 mg/ml to 2.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically salt thereof;
b. a tonicity adjusting agent;
c. a pH adjusting agent; and
d. water for injection,

wherein
(i) the syringe was subjected to terminal sterilization by autoclaving,
(ii) the solution has a pH of 3.0 to 4.5,
(iii) the fill volume is 50 ml, and
(iv) the aqueous solution of midazolam of a pharmaceutically acceptable salt thereof in the syringe remains free of any sub-visible particles at room temperature for at least 6 months.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Kumar Samarth
• Soni Maheshkumar Parasmal
• Patel Nishit
• Kane Prashant
• Bhowmick Subhas Balaram

Classifications

• A61K47/02

  Inorganic compounds · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61J1/1475

  Inlet or outlet ports · CPC title

• A61J1/10

  Bag-type containers · CPC title

• A61P23/00

  Anaesthetics · CPC title