Parenteral dosage form of diltiazem

Patent metadata

Field	Value
Publication number	US-11241379-B2
Application number	US-201615780793-A
Country	US
Kind code	B2
Filing date	Dec 1, 2016
Priority date	Dec 1, 2015
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

The present invention relates to a parenteral dosage form comprising a) a ready-to-infuse, stable aqueous solution comprising diltiazem or its pharmaceutically acceptable salt, pH adjusting agent to provide a pH in the range of 3 to 5 and ethanol, and b) an infusion container filled with said aqueous solution.

First claim

The invention claimed is:

1. A parenteral dosage form comprising:
a. a ready-to-infuse, stable aqueous solution comprising diltiazem or its pharmaceutically acceptable salt, a pH adjusting agent to provide a pH in the range of 3 to 5, and ethanol,
b. an infusion container filled with from about 50 ml to about 500 ml of the aqueous solution,
wherein the aqueous solution is stable at room temperature for at least 6 months or 2°-8° C. for at least 6 months, or both, and has less than 2% of desacetyl diltiazem impurity,
wherein the aqueous solution does not contain glycerol and glycols, and
wherein said dosage form is for parenteral administration.

2. The parenteral dosage form according to claim 1 , wherein the diltiazem or its pharmaceutically acceptable salt is present at a concentration of about 0.4 mg/ml to about 1.0 mg/ml.

3. The parenteral dosage form according to claim 1 , wherein ethanol is present at a concentration ranging from about 1.0% w/v to about 10.0% w/v.

4. The parenteral dosage form according to claim 1 , wherein the infusion container is made of plastic and is flexible.

5. The parenteral dosage form according to claim 1 , wherein the aqueous solution has total impurity of less than 2% when stored at room temperature for at least 6 months.

6. The parenteral dosage form according to claim 1 , wherein the aqueous solution has total impurity of less than 2% when stored at 2° C.-8° C. for at least 6 months.

7. A parenteral dosage form comprising:
a. a ready-to-infuse, stable aqueous solution consisting essentially of diltiazem or its pharmaceutically acceptable salt, a pH adjusting agent to provide a pH in the range of 3 to 5, and ethanol,
b. an infusion container filled with from about 50 ml to about 500 ml of the aqueous solution,
wherein the aqueous solution is stable at room temperature for at least 6 months or 2°-8° C. for at least 6 months, or both, and has less than 2% of desacetyl diltiazem impurity, and
wherein said dosage form is for parenteral administration.

8. The parenteral dosage form according to claim 7 , wherein the diltiazem or its pharmaceutically acceptable salt is present at a concentration of about 0.4 mg/ml to about 1.0 mg/ml.

9. The parenteral dosage form according to claim 7 , wherein ethanol is present at a concentration ranging from about 1.0% w/v to about 10.0% w/v.

10. The parenteral dosage form according to claim 7 , wherein the infusion container is made of plastic and is flexible.

11. The parenteral dosage form according to claim 7 , wherein the aqueous solution has total impurity of less than 2% when stored at room temperature for at least 6 months.

12. The parenteral dosage form according to claim 7 , wherein the aqueous solution has total impurity of less than 2% when stored at 2° C.-8° C. for at least 6 months.

13. A parenteral dosage form comprising:
a. a ready-to-infuse, stable aqueous solution consisting of (a) diltiazem or its pharmaceutically acceptable salt, (b) citric acid to provide a pH in the range of 3 to 5, (c) ethanol, and (d) optionally, sodium citrate,
b. an infusion container filled with from about 50 ml to about 500 ml of the aqueous solution,
wherein the aqueous solution is stable at room temperature for at least 6 months or 2°-8° C. for at least 6 months, or both, and has less than 2% of desacetyl diltiazem impurity,
wherein the aqueous solution does not contain glycerol and glycols, and
wherein the dosage form is for parenteral administration.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Kumar Samarth
• Thakkar Milan Natvarbhai
• Dave Kandarp Maheshkumar

Classifications

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · 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

• A61J1/1406

  Septums, pierceable membranes · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K31/554

  having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem · CPC title