Infusion bag of midazolam for intravenous use

Patent metadata

Field	Value
Publication number	US-11246801-B2
Application number	US-202016865841-A
Country	US
Kind code	B2
Filing date	May 4, 2020
Priority date	Feb 22, 2019
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

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 sterile, ready-to-use multi-layer infusion container having an innermost layer, the container having a stable, aqueous solution of midazolam within the container and in contact with the innermost layer, the solution comprising:
a. midazolam or a pharmaceutically salt thereof;
b. a tonicity adjusting agent;
c. a pH adjusting agent; and
d. water for injection,

wherein the innermost layer does not absorb the midazolam or pharmaceutically acceptable salt thereof, and the innermost layer is comprised of a cyclo-olefin polymer or a cyclo-olefin co-polymer.

2. The sterile, ready-to-use infusion container according to claim 1 , wherein the stable, aqueous solution has a concentration of 0.1 mg/ml to 2.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically acceptable salt thereof.

3. The sterile, ready-to-use infusion container according to claim 1 , wherein the stable, aqueous solution has a concentration of 0.5 mg/ml to 1.0 mg/ml of midazolam or a base equivalent concentration of a pharmaceutically acceptable salt thereof.

4. The sterile, ready-to-use infusion container according to claim 1 , wherein the tonicity adjustment agent is sodium chloride.

5. The sterile, ready-to-use infusion container according to claim 1 , wherein the pH of the stable, aqueous solution is 3.0 to 4.5.

6. The sterile, ready-to-use infusion container according to claim 1 , wherein the pH of the stable, aqueous solution is 3.0 to 4.0.

7. The sterile, ready-to-use infusion container according to claim 1 , wherein the pH of the stable, aqueous solution is 4.0 to 4.5.

8. The sterile, ready-to-use infusion container according to claim 1 , wherein the pH of the stable, aqueous solution is 3.4±0.2.

9. The sterile, ready-to-use infusion container 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.

10. The sterile, ready-to-use infusion container according to claim 1 , wherein the container is a rigid, semi-rigid or a flexible container.

11. The sterile, ready-to-use infusion container according to claim 1 , wherein the container is a flexible bag.

12. The sterile, ready-to-use infusion container according to claim 11 , wherein the wall of the body of said bag comprises at least two layers and wherein the innermost layer is made of a material that does not show adsorption of midazolam on its surface.

13. The sterile, ready-to-use infusion container according to claim 12 , wherein the innermost layer is made-up of a cyclo-olefin polymer or a cyclo-olefin co-polymer.

14. The sterile, ready-to-use infusion container according to claim 11 , wherein the wall of the body of the flexible infusion bag comprises at least three layers, wherein the outermost layer is made of polypropylene (PP), the middle layer is made of linear low density polyethylene (LLDPE), and the innermost layer is made of a cyclo-olefin polymer or a cyclo-olefin co-polymer.

15. The sterile, ready-to-use, infusion container according to claim 1 , wherein the container is terminally sterilized.

16. The sterile, ready-to-use, infusion container according to claim 1 , wherein the container is further overwrapped by an overwrap pouch covering the filled and sealed infusion container.

17. A sterile, ready-to-use infusion container comprising a stable, aqueous solution of Midazolam comprising:
a. midazolam or a pharmaceutically salt thereof;
b. a tonicity adjusting agent;
c. a pH adjusting agent; and
d. water for injection,

wherein the aqueous solution of midazolam or pharmaceutically acceptable salt thereof in the container remains free of any sub-visible particles (nylon particles) at room temperature for at least 6 months.

18. The sterile, ready-to-use infusion container according to claim 1 , wherein said infusion container is a flexible, multi-layered bag comprising:
a. a body filled with about 80 ml to about 500 ml of the stable, aqueous solution of midazolam or a pharmaceutically acceptable salt thereof; and
b. one or more tubes fixed to the body of the infusion bag.

19. The sterile, ready-to-use, infusion container according to claim 1 , wherein the container comprises at least two tubes with one of the at least two tubes fixed to the body of the infusion bag, and wherein one of the at least two tubes is fitted to an outlet port which is designed to attach to a sterile infusion set, and another tube is fitted to an inlet port which is designed to receive a sterile fluid which is with or without a medicament other than midazolam.

20. A method of treating a disease or a condition or providing a supportive medication comprising intravenously administering to a patient in need thereof, a stable, aqueous solution of midazolam or a pharmaceutically acceptable salt thereof from an infusion container of claim 1 .

21. The method according to claim 20 , wherein the disease or condition to be treated or supportive medication to be provided is selected from the group consisting of preoperative sedation, anxiolysis, amnesia, for induction of general anesthesia, and before administration of other anesthetic agents.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

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

Classifications

• A61K31/5517

  condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61J1/1468 Primary

  Containers characterised by specific material properties · CPC title

• A61J1/10

  Bag-type containers · CPC title

• A61K31/55

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