Packaged stable enema solution or suspension containing 5-aminosalicyclic acid

• US 4,664,256 A
• Filed: 10/02/1985
• Issued: 05/12/1987
• Est. Priority Date: 09/06/1983
• Status: Expired

• Current Assignee: Solvay Pharmaceuticals Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Farmaceutisk Laboratorium Ferring A/S
• Inventors: Halskov, Soren
• Primary Examiner(s): Price, William
• Assistant Examiner(s): Foster, Jimmy G.
• Application Number:
  US06/782,159
• Time in Patent Office: 587 Days
• Field of Search: 206/204, 206/205, 206/213.1, 264/55, 264/102, 514/166, 514/159
• US Class Current: 206/213.1
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: B65D 2565/387 Materials used as gas barriers
• CPC Class Codes: Y02W 30/80 Packaging reuse or recycling, e.g. of multilayer packaging bio-packaging Y02W90/10

Abstract

A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA or a pharmaceutically acceptable salt or ester thereof, a chelating agent, an antioxidant and a buffer, the solution or suspension having a pH value of from 4 to 7 and being contained in a plastic bottle under an inert gas, the plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle.

Claims

1. A packaged enema solution or suspension consisting essentially of an effective amount of 5-ASA or a pharmaceutically acceptable salt or ester thereof, a chelating agent, an antioxidant and a buffer, said solution or suspension having a pH value of about 4.8 and being contained in a plastic bottle under an inert gas, said plastic bottle being packaged in a diffusion-tight light-impervious package in the same inert gas as is present in the bottle.

2. A packaged enema solution or suspension according to claim 1, wherein the chelating agent comprises EDTA, the antioxidant comprises sodium pyrosulfite and the buffer comprises citric acid and sodium hydroxide.

3. A packaged enema solution or suspension according to claim 1, wherein the buffer is sodium bicarbonate and hydrochloric acid.

4. An enema solution or suspension according to claim 1, wherein the 5-aminosalicyclic acid is sufficiently pure to avoid autooxidation, having no additional HPLC fluospectrophotometric and spectrophotometric peaks.

5. A packaged enema solution or suspension according to claim 1, wherein the inert gas is argon, nitrogen or carbon dioxide.

6. A packaged enema solution or suspension according to claim 1 consisting essentially of substantially pure 5-aminosalicyclic acid or a pharmaceutically acceptable salt or ester thereof, ethylenediaminetetraacetic acid, sodium pyrosulfite, citric acid, sodium hydroxide and purified water.

7. A packaged enema solution or suspension according to claim 1, wherein the plastic bottle is polyethylene.

8. A packaged enema solution or suspension according to claim 7, wherein a polyethylene granulate used for producing the polyethylene bottle is deoxidized by alternately evacuating the granulate and flooding the granulate with nitrogen gas.

9. A package enema solution or suspension according to claim 8, wherein the deoxidized granulate is extruded, formed into a bottle by means of an inert gas, and the bottle is filled with said enema solution.

10. A package enema solution or suspension according to claim 9, the filled bottle is conveyed directly to a packing chamber wherein the bottle is packed into an aroma-tight bag under an inert gas, said bag being sealed by welding before being contacted with air.

11. A packaged enema solution or suspension according to claim 10, wherein the aroma-tight bag is a plastic aluminum laminate.

12. A packaged enema solution or suspension according to claim 11, containing per 100 ml of solution about 0.2 to 4.0 g 5-aminosalicyclic acid, about 50 mg to 200 mg of sodium pyrosulfite, about 0.5 to 1.5 g citric acid, about 0.5 to 2 g sodium hydroxide, about 5 to 30 mg sodium EDTA, and purified water.

13. A packaged enema solution or suspension according to claim 12, containing per 100 ml of solution about 1 g of 5-aminosalicyclic acid, about 200 mg of sodium pyrosulfite, about 1 g citric acid, about 20 mg sodium EDTA, and sufficient sodium hydroxide and purified water to maintain said pH of 4.8.