Freeze-dried pantoprazole preparation and pantoprazole injection

• US 20030003058A1
• Filed: 07/15/2002
• Published: 01/02/2003
• Est. Priority Date: 11/22/2000
• Status: Active Grant

• Current Assignee: Takeda GmbH (Takeda Pharmaceutical Company Limited)
• Original Assignee: Altana Pharma AG (Takeda Pharmaceutical Company Limited)
• Inventors: Dietrich, Rango, Linder, Rudolf
• Granted Patent: US 6,780,881 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

Lyophilized pantoprazole preparations which are obtainable by freeze-drying of an aqueous solution of pantoprazole, ethylenediamine tetraacetic acid and/or a suitable salt thereof, and sodium hydroxide and/or sodium carbonate are disclosed. The preparations have advantageous properties when reconstituted for injection.

Claims

1. Process for the production of a freeze-dried preparation comprising 5-difluoromethoxy-2-[(3,4-di-methoxy-2-pyridinyl)methylsulfinyl]-1H-benzimidazole (pantoprazole), a salt thereof, a solvate of pantoprazole or a salt thereof, comprising freeze-drying of an aqueous solution of pantoprazole, a salt thereof, a solvate of pantoprazole or a salt thereof, ethylenedlamine tetraacetic acid and/or a suitable salt thereof, and sodium hydroxide and/or sodium carbonate,

2. Process according to claim 1, comprising dissolution of ethylenediamine tetraacetic acid and/or a suitable salt thereof in water, adjusting pH of the solution to 8 or above 8 by addition of sodium hydroxide and/or sodium carbonate and addition of pantoprazole, a salt thereof, a solvate of pantoprazole or a salt thereof, to the thus obtained solution.

3. Process according to claim 1, wherein the proportion by weight of ethylenedlamine tetraacetic acid and/or a suitable salt thereof, based on the amount of pantoprazole present is from 0.05 to 25%, from 0.25 to 12.5%, or from 1 to 5%.

4. Process according to claim 1, wherein pantoprazole is pantoprazole sodium sesquihydrate.

5. Process according to claim 1, wherein the pH of the aqueous solution is in the range from 10 to 13.

6. Process according to claim 1, wherein the pH of the aqueous solution is in the range from 10.5 to 11.5.

7. Process according to claim 1, wherein the pH of the aqueous solution is in the range from 10.75 to 11.25.

8. Process according to claim 1, wherein the pH of the aqueous solution is selected from the group of pH values 10.75, 10.8, 10.85, 10.9, 10.95, 11, 11.05, 11.1, 11.15, 11.2 and 11.25.

9. Lyophilized pantoprazole preparation obtainable by a process according to claims 1 to 8.

10. Pantoprazole injection for bolus administration obtainable by reconstitution of the pantoprazole preparation according to claim 9 in a suitable solvent.

11. Pantoprazole injection according to claim 10, wherein the solvent is physiological saline.

12. Injection kit comprising a lyophilized pantoprazole preparation according to claim 9 and a solvent suitable for bolus administration.

13. Pantoprazole injection having less than 130, preferably less than 120 subvisible particles/per vial, the particles having a size equal to or greater as 10 μ

m, the number of particles determined according to U.S. Pat. No. 24 (<

788>

Particle Matter in Injections) by light obscuration particle test count.