Tetracycline compositions
Compositions, pharmaceutical compositions, and methods for preparing the same, comprising a tetracycline with improved stability and solubility, are disclosed. Some embodiments include a tetracycline with an excess of a divalent or trivalent cation.
1. An intravenous formulation consisting essentially of:
an aqueous solution of minocycline or a salt thereof 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 and less than or equal to about 10:1; and
the formulation has a pH greater than 4 and less than 7.
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 about 10:1.
5. The intravenous formulation of claim 1 , wherein the intravenous formulation has an osmolality less than about 500 mOsm/kg.
6. The intravenous formulation of claim 5 , wherein the osmolality of the solution is less than 400 mOsm/kg.
7. The intravenous formulation of claim 5 , wherein the osmolality of the solution is less than 350 mOsm/kg.
8. 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.
9. The intravenous formulation of claim 1 , wherein the formulation comprises magnesium sulfate.
10. The intravenous formulation of claim 1 , wherein the formulation comprises a base, wherein the base comprises NaOH.
11. The intravenous formulation of claim 1 , wherein the concentration of minocycline is at least 10 mg/mL.
12. The intravenous formulation of claim 1 , wherein the formulation consists of an aqueous solution consisting essentially of minocycline or a salt thereof, magnesium sulfate, and a base, and wherein the formulation has a pH that is greater than 4 and no greater than 6.
13. 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.
14. The intravenous formulation of claim 1 , comprising at least about 100 mg of minocycline or a salt thereof.
15. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
16. The intravenous formulation of claim 1 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
17. The intravenous formulation of claim 8 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
18. The intravenous formulation of claim 8 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
19. The intravenous formulation of claim 9 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
20. The intravenous formulation of claim 9 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
21. The intravenous formulation of claim 12 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
22. The intravenous formulation of claim 12 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
23. The intravenous formulation of claim 1 , wherein the formulation does not contain a pharmaceutically acceptable oil.
24. The intravenous formulation of claim 23 , wherein the molar ratio of magnesium cation to minocycline is between about 5:1 to about 10:1.
25. The intravenous formulation of claim 24 , wherein the formulation has a pH of between about 4.5 and about 5.5.
26. The intravenous formulation of claim 25 , wherein the formulation has an osmolality less than about 500 mOsm/kg.
27. The intravenous formulation of claim 26 , wherein the molar ratio of magnesium cation to minocycline is about 5:1.
28. The intravenous formulation of claim 27 , comprising at least about 130 mg of minocycline.
29. The intravenous formulation of claim 28 , wherein the total volume of the formulation is less than 500 ml.
30. The intravenous formulation of claim 29 , wherein the total volume of the formulation is less than 110 ml.