Pharmaceutical tetracycline composition for dermatological use

1. A topical composition comprising minocycline, a magnesium salt, and a sulfite compound in a non-aqueous solvent, wherein the minocycline is dissolved in the composition and the composition is non-aqueous.

2. The topical composition of claim 1 , wherein the non-aqueous solvent comprises a monohydric aliphatic alcohol and a polyol.

3. The topical composition of claim 2 , wherein the ratio between the monohydric aliphatic alcohol and the polyol is in the range of 1:1 to 99:1 by weight.

4. The topical composition of claim 3 , comprising a greater percentage by weight of the monohydric aliphatic alcohol than the polyol.

5. The topical composition of claim 4 , wherein the w/w ratio of monohydric aliphatic alcohol and polyol is in a range of about 2:1 to 10:1 by weight.

6. The topical composition of claim 1 , wherein the molar ratio of the magnesium salt to the minocycline is in a range of about 2:1 to 100:1.

7. The topical composition of claim 1 , wherein the magnesium salt is magnesium chloride, or is a minocycline salt having a counter ion that is softer than chloride.

8. The topical composition of claim 1 , wherein the monohydric aliphatic alcohol is selected from the group consisting of ethanol, isopropanol, propyl alcohol, tert-butyl alcohol, or combinations thereof.

9. The topical composition of claim 8 , wherein the monohydric aliphatic alcohol is ethanol.

10. The topical composition of claim 1 , comprising from about 0.1% to about 4% by weight minocycline.

11. The topical composition of claim 1 , which when stored at 40° C. in a closed glass vial for a period of 4 weeks, exhibits an increase in the relative concentration of 4-epi-minocycline of less than 1.0% per week.

12. The topical composition of claim 2 , which when stored at 40° C. in a closed glass vial for a period of 4 weeks, exhibits an increase in the relative concentration of 4-epi-minocycline of less than 0.70% per week.

13. The topical composition of claim 1 , which when stored at 25° C. and 60% relative humidity in a sealed container for 12 months, contains less than 7% minocycline degradation product, where the degradation product is 4-epi-minocycline.

14. The topical composition of claim 2 , wherein the polyol is a C3-C8 diol or a triol.

15. The topical composition of claim 14 , wherein the polyol is propylene glycol.

16. The topical composition of claim 1 , wherein the sulfite compound is a sulfite, bisulfite, pyrosulfite, or metabisulfite.

17. The topical composition of claim 16 , wherein the sulfite compound is an inorganic sulfite salt comprising an inorganic cation selected from sodium, potassium, calcium and magnesium.

18. The topical composition of claim 1 comprising from about 0.005% to about 3.0% by weight of the sulfite compound.

19. The topical composition of claim 18 , wherein the sulfite is selected from the group consisting of sodium sulfite, sodium bisulfite, and sodium meta-bisulfite.

20. The topical composition of claim 1 , comprising less than about 3 weight percent water.

21. The topical composition of claim 20 , comprising less than about 2 weight percent water.

22. The topical composition of claim 1 , further comprising an essential oil.

23. The topical composition of claim 22 , comprising 0.01 to 5 weight percent of 1,8-cineole.

24. The topical composition of claim 1 , comprising a thickening agent.

25. The topical composition of claim 24 , wherein the thickening agent is hydroxypropyl cellulose.

26. The topical composition of claim 1 , wherein the composition is not an emulsion and/or does not comprise nanoparticles or microparticles.

27. 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.

28. The topical composition of claim 27 , having an effective pH of about 3.8 to about 5.0 when mixed with water in a ratio of 1:9 by weight.

29. The topical composition of claim 1 , wherein the non-aqueous solvent comprises a monohydric aliphatic alcohol.

30. The topical composition of claim 1 , wherein the composition is non-irritating when applied to rats daily over a period of 28 days.

31. 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.

32. The topical composition of claim 31 , 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 =((Δ R ) 2 +(Δ G ) 2 +(Δ B ) 2 ) 0.5 .

33. A topical composition comprising a tetracycline-class drug, a magnesium salt, a monohydric aliphatic alcohol and a polyol, wherein (i) the ratio between the monohydric aliphatic alcohol and the polyol is in a range of 1:1 to 99:1 by weight, and (ii) the tetracycline-class drug is dissolved in the topical composition,

wherein the topical composition is non-aqueous.

34. The topical composition of claim 33 , wherein the polyol is propylene glycol.

35. The topical composition of claim 33 , further comprising an antioxidant.

36. The topical composition of claim 33 , wherein the tetracycline class drug is minocycline.

37. The topical composition of claim 33 , wherein the composition is hydrophilic.

38. The topical composition of claim 33 , wherein the penetration efficiency into ex vivo human facial skin is equal to or exceeds 5%.

39. A method for treating a dermatological inflammation or infection comprising applying the topical composition of claim 1 to an exterior epithelial surface of a mammalian body in need thereof at least once daily for a period of at least 1 week.

40. A method for treating a dermatological inflammation or infection comprising applying the topical composition of claim 1 to an exterior epithelial surface of a mammalian body in need thereof at least once daily for a period of at least 1 month.

41. A method for making a topical composition, the method comprising (i) combining minocycline, a magnesium salt, and a sulfite compound in a non-aqueous solvent to form a mixture, and (ii) agitating the mixture from (i) to form a solution in which the minocycline is dissolved, thereby obtaining a composition of claim 1 .

42. A method for making a topical composition, the method comprising (i) combining a tetracycline-class drug, a magnesium salt, a volatile monohydric aliphatic alcohol, and a polyol to form a mixture, and (ii) agitating the mixture from (i) to form a solution in which the tetracycline-class drug is dissolved, thereby obtaining a composition of claim 33 .