Pharmaceutical tetracycline composition for dermatological use
Provided herein is a topical composition and related methods for making and using the composition. In a first aspect, the topical composition comprises minocycline, a magnesium salt, and a sulfite compound in a non-aqueous solvent. In yet another aspect, the topical composition comprises a tetracycline-class drug, a source of magnesium, a monohydric aliphatic alcohol, and a polyol, wherein (i) the ratio between the monohydric aliphatic alcohol and the propylene glycol is in the range of 1:1 to 99:1 by weight and (ii) the tetracycline-class drug is dissolved in the topical composition.
1. A topical composition, comprising:
minocycline,
a divalent cation,
a sulfite compound, and
a solvent;
wherein
the minocycline is dissolved in the composition; and
the relative concentration of 4-epi-minocycline in the composition is less than 5.0% after storage at 40° C. in a sealed glass vial for 4 weeks.
2. The topical composition of claim 1 , wherein the relative concentration of 4-epi-minocycline increases less than 1.00% per week when stored at 40° C. in a sealed glass vial for 4 weeks.
3. The topical composition of claim 1 , wherein the relative concentration of 4-epi-minocycline is 0.50% to 1.00% prior to storage and increases 0.20% to 0.40% when stored at 40° C. in a sealed glass vial for 4 weeks.
4. The topical composition of claim 1 , wherein the relative concentration of 4-epi-minocycline is 0.50% to 1.00% prior to storage and increases 0.20% to 0.40% when stored at 40° C. in a sealed glass vial for 4 weeks.
5. The topical composition of claim 1 , wherein
the solvent comprises ethanol,
the divalent cation is a magnesium cation, and
the composition comprises less than 5% water as measured by Karl Fischer titration.
6. The topical composition of claim 5 , wherein the composition comprises less than 3% water as measured by Karl Fischer titration.
7. The topical composition of claim 5 , wherein the composition comprises less than 2% water as measured by Karl Fischer titration.
8. The topical composition of claim 5 , wherein the composition comprises less than 1% water as measured by Karl Fischer titration.
9. The topical composition of claim 5 , wherein the composition comprises 0.5% to 1.0% water as measured by Karl Fischer titration.
10. The topical composition of claim 1 , wherein the solvent comprises a monohydric aliphatic alcohol and a polyol.
11. The topical composition of claim 10 , wherein the ratio of the monohydric aliphatic alcohol to the polyol is in the range of 1:1 to 99:1 by weight.
12. The topical composition of claim 10 , wherein the ratio of the monohydric aliphatic alcohol to the polyol is in the range of 2:1 to 10:1 by weight.
13. The topical composition of claim 1 , wherein the molar ratio of the divalent cation to the minocycline is in a range of about 2:1 to 100:1.
14. The topical composition of claim 10 , wherein the monohydric aliphatic alcohol is selected from the group consisting of ethanol, isopropanol, propyl alcohol, tert-butyl alcohol, and combinations thereof.
15. The topical composition of claim 10 , wherein the monohydric aliphatic alcohol is ethanol.
16. The topical composition of claim 10 , wherein the polyol is a C3-C8 diol or a triol.
17. The topical composition of claim 16 , wherein the polyol is propylene glycol.
18. The topical composition of claim 1 , wherein the sulfite compound is a sulfite, bisulfite, pyrosulfite, or metabisulfite.
19. The topical composition of claim 18 , wherein the sulfite compound is an inorganic sulfite salt comprising an inorganic cation selected from sodium, potassium, calcium and magnesium.
20. The topical composition of claim 18 , wherein the sulfite is selected from the group consisting of sodium sulfite, sodium bisulfite, and sodium meta-bisulfite.
21. The topical composition of claim 1 , comprising from about 0.005% to about 3.0% by weight of the sulfite compound.
22. The topical composition of claim 1 , comprising from about 0.1% to about 4% by weight of the minocycline.
23. The topical composition of claim 1 , further comprising an essential oil.
24. The topical composition of claim 23 , comprising 0.01 to 5 weight percent of 1,8-cineole.
25. The topical composition of claim 1 , wherein the composition is not an emulsion and/or does not comprise nanoparticles or microparticles.
26. The topical composition of claim 1 , having an effective pH of 3-6 when mixed with water in a ratio of 1:9 by weight.
27. The topical composition of claim 1 , wherein the composition exhibits no significant change in color after aging for 4 weeks at 40° C. in a sealed container.
28. The topical composition of claim 27 , wherein no significant color change is a color change of less than 20 in distance in 3-dimensional RGB space where each value is measured on a 0-255 range and distance is calculated in 3-dimensional RGB space according to the following formula: distance RGB =((ΔR) 2 +(ΔG) 2 +(ΔB) 2 ) 0.5 .
29. The topical composition of claim 1 , wherein the composition is hydrophilic.
30. A method for treating an active dermatological inflammation or infection comprising applying the topical composition of claim 1 to an inflamed or infected area of skin of a human at least once daily for a period of at least 1 month.
31. The method of claim 30 wherein the active dermatological inflammation or infection is acne.
32. The method of claim 30 wherein the active dermatological inflammation or infection is rosacea.