Parenteral unit dosage form of dihydroergotamine

Patent metadata

Field	Value
Publication number	US-12533351-B2
Application number	US-202318305527-A
Country	US
Kind code	B2
Filing date	Apr 24, 2023
Priority date	Aug 27, 2018
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

A parenteral unit dosage form comprising an aqueous solution of dihydroergotamine or pharmaceutically acceptable salt thereof as a sole active ingredient, one or more pH adjusting agents, and optionally one or more co-solvents, wherein the pH of the aqueous solution is such that it contains substantially lower amount of impurity of Formula I and impurity of Formula II as compared to aqueous solution having a pH of 4.0 or less, when the parenteral unit dosage form is stored at 25° C. and 60% relative humidity for at least three months.

First claim

We claim:

1 . A parenteral unit dosage form comprising an aqueous solution of dihydroergotamine or a pharmaceutically acceptable salt thereof as a sole active ingredient, and one or more pH adjusting agents,
wherein: the pH of the aqueous solution is in the range of 4.1 to 4.9, the solution is contained in an auto-injector or a prefilled syringe, the solution does not require reconstitution or dilution prior to subcutaneous administration, and when said parenteral unit dosage form is stored in a pouch at 25° C. and 60% relative humidity for three months, an increase in total amount of impurities as compared to an initial amount of impurities is less than 2.6% by weight.

2 . The parenteral unit dosage form according to claim 1 , wherein the pH of the aqueous solution is in the range of 4.2 to 4.8.

3 . The parenteral unit dosage form according to claim 1 , wherein the aqueous solution is free of preservative or complexing agent.

4 . The parenteral unit dosage form according to claim 1 , wherein the pharmaceutical acceptable salt of dihydroergotamine is dihydroergotamine mesylate and it is present at a concentration ranging from 0.5 to 1.5 mg/ml.

5 . The parenteral unit dosage form according to claim 1 , wherein, when said parenteral unit dosage form is stored in a pouch at 40° C. and 75% relative humidity for three months, an increase in total amount of impurities as compared to an initial amount of impurities is less than 1.7% by weight.

6 . The parenteral unit dosage form according to claim 1 , wherein, when said parenteral unit dosage form is stored in a pouch at 25° C. and 60% relative humidity for three months, the dosage form contains impurity of Formula I in an amount less than 0.25% by weight

7 . The parenteral unit dosage form according to claim 1 , wherein, when the parenteral unit dosage form is stored in a pouch at 40° C. and 75% relative humidity for three months, the dosage form contains impurity of Formula I in an amount less than 0.7% by weight.

8 . The parenteral unit dosage form according to claim 1 , wherein, when the parenteral unit dosage form is stored in a pouch at 25° C. and 60% relative humidity for three months, the dosage form contains impurity of Formula II in an amount less than 1.4% weight

9 . The parenteral unit dosage form according to claim 1 , further comprising one or more co-solvents.

10 . The parenteral unit dosage form of claim 1 , wherein the dosage form is packaged in an atmosphere containing less than 1% oxygen.

11 . The parenteral unit dosage form of claim 1 , wherein the dosage form is packaged with an oxygen scavenger.

12 . The parenteral unit dosage form of claim 1 , wherein the dosage form is packaged in a pouch.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Goyani Alpesh
• Singodia Deepak
• Pallerla Bhaskar
• Agrawal Sudeep Kumar
• Bhowmick Subhas Balaram
• Thennati Rajamannar

Classifications

• A61P25/06

  Antimigraine agents · CPC title

• A61M5/20

  Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically (A61M5/142 {, A61M5/46} take precedence; {hypodermic projectiles F42B12/54}) · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K9/0019

  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