Antibiotic formulations, unit doses, kits, and methods

• US 9,895,386 B2
• Filed: 04/29/2016
• Issued: 02/20/2018
• Est. Priority Date: 09/29/2005
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Charan, Chatan, Dwivedi, Sarvajna
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US15/143,009
• Publication Number:
  US 20160317562A1
• Time in Patent Office: 662 Days
• CPC Class Codes: A61J 1/065 Rigid ampoules, e.g. glass ampoules
• CPC Class Codes: A61J 1/1412 Containers with closing means, e.g. caps
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7034 attached to a carbocyclic compound, e.g. phloridzin
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• 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 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/08 Solutions composition of solutions 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: A61M 11/001 Particle size control
• CPC Class Codes: A61M 16/04 Tracheal tubes catheters in general A61M25/00
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An aqueous or powder composition includes anti-gram-negative antibiotic or salt thereof being present at an amount ranging from about 100 mg/ml to about 200 mg/ml. Another aqueous or powder composition includes anti-gram-positive antibiotic or salt thereof being present at a concentration ranging from about 0.6 to about 0.9 of the water solubility limit, at 25° C. and 1.0 atmosphere, of the anti-gram-positive antibiotic or salt thereof. Other embodiments include unit doses, kits, and methods.

Claims

1. A method of producing a unit dose of an aqueous amikacin composition comprising:

a) preparing an amikacin solution by dissolving amikacin sulfate in preservative-free water by stirring;

b) adjusting the pH of the amikacin solution, if necessary, until the pH of the solution is between about 5.5 and 6.3; and

c) adding about 3 to 10 ml of the amikacin solution to a container in order to generate a unit dose;

wherein the unit dose comprises a preservative-free liquid composition for aerosolization having a pH of about 5.5 to about 6.3 and a shelf life of at least two years at room temperature without the formation of precipitate, wherein the unit dose consists essentially of water and about 400 mg to about 750 mg amikacin, at a concentration of about 125 mg/ml; and

wherein the unit dose has an osmolarity ranging from about 90 mOsmol/kg to about 500 mOsmol/kg and a potency of amikacin, from about 500 μ

g/mg to about 1100 μ

g/mg.

2. The method of claim 1, wherein the container is in a nebulizer.

3. The method of claim 2, wherein the nebulizer is a vibrating mesh nebulizer.

4. The method of claim 1, wherein about 3 to 6 ml of the amikacin solution is added to the container in step c).

5. The method of claim 1, wherein the container is an ampoule.

6. The method of claim 1 or 5, wherein the container comprises a blow-fill seal.

7. The method of claim 1, wherein the container comprises a vial.

8. The method of claim 1, wherein the container comprises a glass bottle.

9. The method of claim 1, wherein the rubber stopper is a rubber siliconized stopper.

10. A unit dose of an aqueous amikacin composition, wherein the unit dose is prepared according to a method comprising the steps of:

a) preparing an amikacin solution by dissolving amikacin sulfate in preservative-free water for injection by stirring;

b) adjusting the pH of the amikacin solution, if necessary, until the pH of the solution is between about 5.5 and 6.3; and

c) adding about 3 to 10 ml of the amikacin solution to a container in order to generate a unit dose;

wherein the unit dose comprises a preservative-free liquid composition for aerosolization having a pH of about 5.5 to about 6.3 and a shelf life of at least two years at room temperature without the formation of precipitate, wherein the unit dose consists essentially of water and about 400 mg to about 750 mg amikacin, at a concentration of about 125 mg/ml; and

wherein the unit dose has an osmolarity ranging from about 90 mOsmol/kg to about 500 mOsmol/kg and a potency of amikacin, from about 500 μ

g/mg to about 1100 μ

g/mg.