Aerosol fluoroquinolone formulations for improved pharmacokinetics
View Patent ↗The present invention relates to the field of antimicrobial agents. In particular, the present invention relates to the use of aerosolized fluoroquinolones formulated with divalent or trivalent cations and having improved pulmonary availability for the treatment and management of bacterial infections of the lung and upper respiratory tract.
1. A pharmaceutical composition, comprising an aqueous solution consisting essentially of from about 75 mg/ml to about 150 mg/ml levofloxacin or ofloxacin and from about 160 mM to about 240 mM of a divalent or trivalent cation, wherein the solution has a pH from about 5 to about 7 and an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg.
2. The composition of claim 1 , wherein the levofloxacin or ofloxacin is present at a concentration from about 80 mg/ml to about 120 mg/ml.
3. The composition of claim 1 , wherein the solution consists essentially of from about 90 mg/ml to about 110 mg/ml levofloxacin and from about 180 mM to about 220 mM of a divalent or trivalent cation.
4. The composition of claim 1 , wherein the solution has a pH from about 6.0 to about 6.5 and an osmolality from about 350 mOsmol/kg to about 400 mOsmol/kg.
5. The composition of claim 1 , wherein the solution consists of 80 mg/ml to 120 mg/ml levofloxacin and from about 160 mM to about 240 mM of a divalent or trivalent cation.
6. The composition of claim 1 , wherein the divalent or trivalent cation is selected from magnesium, calcium, zinc, copper, aluminum, and iron.
7. The composition of claim 1 , wherein the divalent or trivalent cation is selected from magnesium chloride, magnesium sulfate, zinc chloride, and copper chloride.
8. The composition of claim 1 , wherein the aqueous solution lacks a conventional pharmaceutical carrier or excipient selected from the group consisting of mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, and magnesium carbonate.
9. A pharmaceutical composition comprising an aqueous solution consisting essentially of from about 80 mg/ml to about 120 mg/ml levofloxacin or ofloxacin and from about 175 mM to about 225 mM of a divalent or trivalent cation selected from the group consisting of magnesium, calcium, zinc, copper, aluminum, and iron; wherein the solution has a pH from about 5 to about 7 and an osmolality from about 300 mOsmol/kg to about 500 mOsmol/kg.
10. The pharmaceutical composition of claim 9 , wherein the divalent or trivalent cation is magnesium.
11. The composition of claim 9 , wherein the aqueous solution consists of the levofloxacin or ofloxacin and the divalent or trivalent cation.
12. The composition of claim 9 , wherein the solution has a pH from about 6.0 to about 6.5 and an osmolality from about 350 mOsmol/kg to about 400 mOsmol/kg.
13. The composition of claim 9 , wherein the solution consists essentially of from about 80 mg/ml to about 120 mg/ml levofloxacin and from about 175 mM to about 225 mM of a divalent or trivalent cation selected from the group consisting of magnesium, calcium, zinc, copper, aluminum, and iron.
14. A pharmaceutical composition comprising an aqueous solution consisting essentially of from about 90 mg/ml to about 110 mg/ml of levofloxacin and from about 190 mM to about 210 mM of magnesium chloride; wherein the solution has a pH from about 5 to about 7 and an osmolality from about 350 mOsmol/kg to about 400 mOsmol/kg.
15. The composition of claim 14 , wherein the aqueous solution consists essentially of about 100 mg/ml of levofloxacin and about 200 mM magnesium chloride.
16. The composition of claim 14 , wherein the aqueous solution has a pH from about 6.0 to about 6.5.
17. The composition of claim 14 , wherein the aqueous solution consists of the levofloxacin and the magnesium chloride.