Tetracycline compositions
The present invention relates to compositions, pharmaceutical compositions, and methods for preparing the same, comprising a tetracycline with improved stability and solubility. Some embodiments include a tetracycline with an excess of a divalent or trivalent cation.
1. An intravenous formulation comprising:
an aqueous solution of a single antibiotic ingredient and a magnesium cation;
wherein:
the single antibiotic ingredient is minocycline;
the molar ratio of the magnesium cation to the minocycline is greater than 4:1;
the formulation has a pH greater than 4 and less than 7; and
administration of the intravenous formulation results in reduced injection site hemolysis relative to intravenous administration of a control intravenous formulation that does not include magnesium.
2. The intravenous formulation of claim 1 , wherein the formulation has a pH of greater than 4 and less than 6.
3. The intravenous formulation of claim 1 , wherein the formulation has a pH of greater than 4.5 and less than 5.
4. The intravenous formulation of claim 1 , wherein the molar ratio of the magnesium cation to minocycline is greater than 10:1.
5. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is about 11:1.
6. The intravenous formulation of claim 1 , wherein the intravenous formulation has an osmolality less than about 500 mOsm/kg.
7. The intravenous formulation of claim 6 , wherein the osmolality of the solution is less than 400 mOsm/kg.
8. The intravenous formulation of claim 6 , wherein the osmolality of the solution is less than 350 mOsm/kg.
9. The intravenous formulation of claim 1 , wherein the formulation comprises a magnesium salt selected from the group consisting of magnesium sulfate, magnesium oxide, magnesium acetate, magnesium bromide, magnesium malate, magnesium citrate, magnesium chloride, magnesium malate, magnesium citrate, and magnesium acetate.
10. The intravenous formulation of claim 1 , wherein the formulation comprises magnesium sulfate.
11. The intravenous formulation of claim 1 , wherein the formulation comprises abase.
12. The intravenous formulation of claim 11 , wherein the base comprisesNaOH.
13. The intravenous formulation of claim 1 , wherein the concentration of minocycline is at least 10 mg/mL.
14. The intravenous formulation of claim 1 , wherein the formulation consists of an aqueous solution consisting of minocycline or a salt thereof, a salt that comprises a magnesium cation, and a base, and wherein the formulation has a pH that is no less than 4 and no greater than 6.
15. The intravenous formulation of claim 1 , wherein the formulation does not comprise a component selected from the group consisting of polyoxyethylene hydrogenated castor oil, an antioxidant, a pyridine-containing compound, nicotinamide, an alcohol, glycerol, polyethylene glycol, gluconate, a pyrrolidone compound, a water-miscible local anaesthetic, procaine, urea, lactose, and a dehydrating agent selected from the group consisting of ethyl acetate, acetic anhydride, absolute ethanol, and mixtures thereof.
16. The intravenous formulation of claim 1 , comprising at least about 100 mg of the single antibiotic ingredient.
17. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 30:1.
18. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
19. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
20. The intravenous formulation of claim 9 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
21. The intravenous formulation of claim 9 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
22. The intravenous formulation of claim 10 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
23. The intravenous formulation of claim 10 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
24. The intravenous formulation of claim 14 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
25. The intravenous formulation of claim 14 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.