Antibiotic Formulations, Unit Doses, Kits, and Methods

• US 20090288658A1
• Filed: 12/22/2008
• Published: 11/26/2009
• Est. Priority Date: 09/29/2005
• Status: Abandoned Application

• Current Assignee: Bayer Healthcare AG (Bayer AG)
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Charan, Chatan, Dwivedi, Sarvajna
• Application Number:
  US12/341,780
• Publication Number:
  US 20090288658A1
• Time in Patent Office: Days
• US Class Current: 128/200.140
• 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. An aqueous composition for aerosolization comprising amikacin being present at an amount from about 100 mg/ml to about 200 mg/ml.

2. The aqueous composition of claim 1, wherein the aqueous composition consists essentially of amikacin and water.

3. The aqueous composition of claim 1, wherein the amount amikacin is from about 110 mg/ml to about 150 mg/ml, or a potency from about 500 μ

g/mg to about 1100 μ

g/mg, or both.

4. The aqueous composition of claim 1, wherein the aqueous composition has a pH from about 4 to about 6.

5. The aqueous composition of claim 1, wherein the aqueous composition has an osmolality ranging from about 90 mOsmol/kg to about 500 mOsmol/kg.

6. The aqueous composition of claim 1, wherein the aqueous composition is preservative-free.

7. The aqueous composition of claim 1, further comprising an additional active agent.

8. The aqueous composition of claim 1, further comprising an additional active agent selected from an anti-inflammatory and a bronchodilator.

9. The aqueous composition of claim 1, further comprising a bronchodilator selected from β

-agonist, anti-muscarinic agent, and steroid.

10. The aqueous composition of claim 1, further comprising albuterol.

11. The aqueous composition of claim 1, further comprising an osmolality adjuster.

12. The aqueous composition of claim 1, wherein no precipitate forms in the aqueous composition when the aqueous composition is stored for 1 year at 25°

C.

13. The aqueous composition of claim 1, further comprising an anti-gram positive antibiotic.

14. An aqueous composition, consisting essentially of amikacin, a bronchodilator, and water.

15. The aqueous composition of claim 14, wherein the amikacin is present in an amount ranging from about 100 mg/ml to about 200 mg/ml.

16. The aqueous composition of claim 14, wherein the aqueous composition has a pH from about 3 to about 7, and an osmolality from about 90 mOsmol/kg to about 500 mOsmol/kg.

17. The aqueous composition of claim 14, wherein the bronchodilator is present in an amount of at least about 1 mg/ml.

18. The aqueous composition of claim 17, wherein the bronchodilator is selected from a β

-agonist, anti-muscarinic agent, and steroid.

19. The aqueous composition of claim 18, wherein the bronchodilator comprises albuterol or salt thereof.

20. A unit dose, comprising a container and an aqueous composition comprising amikacin, wherein the composition is preservative free.

21. The unit dose of claim 20, wherein the amikacin is present at a concentration from about 90 mg/ml to about 200 mg/ml.

22. A kit, comprising:

a first container containing a first aqueous solution comprising a first antibiotic; and

a second container containing a second aqueous solution comprising a second antibiotic,

wherein the first antibiotic is amikacin and the second antibiotic is the same or different, and wherein a concentration, or an amount, or both of the first antibiotic is the same as, or different from a concentration, or an amount, or both of the second antibiotic.

23. The kit of claim 22, wherein an amount of the first aqueous solution is from about 2 ml to about 5 ml, an amount of the second aqueous solution is from about 5 ml to about 8 ml, a concentration of first antibiotic is from about 100 mg/ml to about 120 mg/ml, and a concentration of second antibiotic is from about 120 mg/ml to about 140 mg/ml.

24. The kit of claim 23, further comprising an aerosol introducer.

26. A kit, comprising:

a first container containing a first aqueous solution comprising amikacin; and

a second container containing a second aqueous solution comprising an anti-gram-negative antibiotic,

wherein a concentration, an amount, or both, of the amikacin of the first aqueous solution is different from a concentration, or an amount, or both, of the anti-gram-negative antibiotic of the second aqueous solution.

25. The kit of claim 28, further comprising a vibrating mesh nebulizer.

27. The kit of claim 26, further comprising an aerosol introducer.

28. The kit of claim 27, further comprising a vibrating mesh nebulizer.

29. A kit, comprising:

a first container containing a first antibiotic comprising liquid amikacin; and

a second container containing a second antibiotic or salt thereof,

wherein the first and second antibiotics are the same or different, and wherein a concentration, or an amount, or both of the first antibiotic in the first container is different from a concentration, or an amount, or both, of the second antibiotic or salt thereof in the second container.

30. The kit of claim 29, wherein the second antibiotic comprises a liquid.

31. The kit of claim 29, wherein the second antibiotic comprises a powder.

32. The kit of claim 30, wherein the liquid amikacin is preservative-free.

33. The kit of claim 29, further comprising an aerosol introducer.

34. The kit of claim 33, further comprising a vibrating mesh nebulizer.

35. A method of administering an antibiotic formulation to a patient in need thereof, comprising:

aerosolizing a liquid amikacin formulation to administer the antibiotic formulation to the pulmonary system of the patient, wherein the antibiotic formulation has a concentration of amikacin ranging from about 100 mg/ml to about 200 mg/ml.

36. The method of claim 35, wherein the antibiotic formulation consists essentially of amikacin and water.

37. The method of claim 35, wherein the aerosolizing comprises forming droplets having a mass median aerodynamic diameter of less than about 10 μ

m.

38. The method of claim 37, wherein the aerosolizing comprises aerosolizing the antibiotic formulation in a vibrating mesh nebulizer.

39. The method of claim 35, wherein the pulmonary administration comprises prophylactic treatment of ventilator associated pneumonia.

40. A method of administering an antibiotic formulation to a patient in need thereof, comprising:

inserting a tube into a trachea of a patient; and

aerosolizing an antibiotic formulation to administer the antibiotic formulation to the lungs of the patient,

wherein the antibiotic formulation consists essentially of amikacin and water.

41. The method of claim 40, wherein the pulmonary administration comprises prophylactic treatment of ventilator associated pneumonia, hospital associated pneumonia, community acquired pneumonia, or combinations thereof.

42. The method of claim 40, wherein the aerosolizing comprises aerosolizing the antibiotic formulation in a vibrating mesh nebulizer.