Aerosolized fluoroquinolones and uses thereof

• US 8,524,735 B2
• Filed: 10/22/2009
• Issued: 09/03/2013
• Est. Priority Date: 05/18/2005
• Status: Active Grant

• Current Assignee: Horizon Therapeutics US Holding LLC (Amgen Inc.)
• Original Assignee: MPEX Pharmaceuticals Incorporated (Abbvie Incorporated)
• Inventors: Surber, Mark W., Bostian, Keith A., Dudley, Michael N., Lomovskaya, Olga, Griffith, David C.
• Primary Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US12/604,347
• Publication Number:
  US 20100037890A1
• Time in Patent Office: 1,412 Days
• Field of Search: 514/279, 514/294, 424/405, 424/602, 424/641, 424/646, 424/677, 424/681, 424/682
• US Class Current: 514/294
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• 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 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed herein are formulations of fluoroquinolones suitable for aerosolization and use of such formulations for aerosol administration of fluoroquinolone antimicrobials for the treatment of pulmonary bacterial infections. In particular, inhaled levofloxacin specifically formulated and delivered for bacterial infections of the lungs is described. Methods include inhalation protocols and manufacturing procedures for production and use of the compositions described.

Claims

1. A kit comprising:

a sterile single use container comprising an aqueous solution of levofloxacin or ofloxacin and a divalent or trivalent cation, wherein the solution is suitable for inhalation into a lung; and

a nebulizer adapted to receive solution from the container and to aerosolize the solution for delivery to the lung through oral inhalation.

2. The kit of claim 1, wherein the nebulizer operates by ultrasonic atomization.

3. The kit of claim 1, wherein the nebulizer operates by hydraulic atomization.

4. The kit of claim 1, wherein the nebulizer operates by a vibrating mesh.

5. The kit of claim 1, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.

6. The kit of claim 1, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.

7. The kit of claim 1, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.

8. The kit of claim 1, wherein the solution comprises levofloxacin at a concentration from about 100 mM to about 625 mM and magnesium chloride at a concentration from about 125 mM to about 250 mM, has a pH from about 5.5 to about 6.5, and an osmolality from about 350 mOsmol/kg to about 750 mOsmol/kg.

9. A system, comprising:

a reservoir comprising an aqueous solution of levofloxacin or ofloxacin and a divalent or trivalent cation, wherein the solution is suitable for inhalation into a lung; and

a nebulizer configured to aerosolize the solution for delivery to the lung through oral inhalation.

10. The system of claim 9, wherein the nebulizer operates by ultrasonic atomization.

11. The system of claim 9, wherein the nebulizer operates by hydraulic atomization.

12. The system of claim 9, wherein the nebulizer operates by a vibrating mesh.

13. The system of claim 9, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.

14. The system of claim 9, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.

15. The system of claim 9, wherein the nebulizer is adapted to produce particles having a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.

16. The system of claim 9, wherein the solution comprises levofloxacin at a concentration from about 100 mM to about 625 mM and magnesium chloride at a concentration from about 125 mM to about 250 mM, has a pH from about 5.5 to about 6.5, and an osmolality from about 350 mOsmol/kg to about 750 mOsmol/kg.