Compositions And Methods For The Preparation And Administration Of Poorly Water Soluble Drugs

1 . A formulation for parenteral administration to a mammal comprising dimethyl isosorbide and a substantially insoluble active pharmaceutical ingredient selected from the group consisting of an ansamycin-derived antineoplastic agent, discodermolide, discodermolide analogs, an epothilone, actinomycin, an actinomycin analog, and combinations thereof.

2 . The formulation of claim 1 , wherein the active pharmaceutical ingredient is an ansamycin-derived antineoplastic agent.

3 . The formulation of claim 2 , wherein the ansamycin-derived antineoplastic agent is selected from the group consisting of geldanmycin, a geldanmycin derivative and a geldanmycin analog.

4 . The formulation of claim 1 , wherein the active pharmaceutical ingredient is an epothilone.

5 . The formulation of claim 4 , wherein the epothilone is selected from the group consisting of epothilone A, epothilone B (EPO906), deoxyepothilone B, epothilone B lactam (BMS-247550) and epothilone D.

6 . The formulation of claim 1 , wherein the active pharmaceutical ingredient is discodermolide.

7 . The formulation of claim 1 , wherein the active pharmaceutical ingredient is a discodermolide analog.

8 . The formulation of claim 7 , wherein the discodermolide analog is selected from the group consisting of 2-epi-discodermolide, 2-des-methyldiscodermolide, 5-hydroxymethyldiscoder-molide, 19-des-aminocarbonyldiscodermolide, 9(13)-cyclodiscodermolide, and laulimalide.

9 . The formulation of claim 1 , wherein the active pharmaceutical ingredient is an actinomycin analog.

10 . The formulation of claim 9 , wherein the actinomycin analog is selected from the group consisting of actinomycin A, C, C3 antibiotic complex, F1, F3, and Z complex.

11 . The formulation of claim 1 , wherein the formulation is nonaqueous.

12 . The formulation of claim 1 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

13 . The formulation of claim 1 , wherein dimethyl isosorbide is present in an amount of from about 0.2 to about 75% w/v of the composition.

14 . The formulation of claim 13 , wherein said dimethyl isosorbide is present in an amount of from about 0.2 to about 75% w/v of the composition and said composition comprises a pharmaceutically-acceptable aqueous solution in an amount of from about 0.2 to about 98% w/v.

15 . The formulation of claim 2 , wherein the formulation is nonaqueous.

16 . The formulation of claim 2 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

17 . The formulation of claim 4 , wherein the formulation is nonaqueous.

18 . The formulation of claim 4 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

19 . The formulation of claim 6 , wherein the formulation is nonaqueous.

20 . The formulation of claim 6 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

21 . The formulation of claim 7 , wherein the formulation is nonaqueous.

22 . The formulation of claim 7 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

23 . The formulation of claim 9 , wherein the formulation is nonaqueous.

24 . The formulation of claim 9 , the formulation further comprising a pharmaceutically-acceptable aqueous solution.

25 . The formulation according to claim 14 , wherein the formulation comprises about 0.1 to about 5 wt. % active pharmaceutical ingredient, about 50 to about 80% w/v DMI, and from about 20 to about 50% w/v aqueous solution.

26 . A method of solubilizing a substantially water-insoluble active pharmaceutical ingredient comprising dissolving the active pharmaceutical ingredient in dimethyl isosorbide, wherein the active pharmaceutical ingredient is selected from the group consisting of an ansamycin-derived antineoplastic agent, discodermolide, a discodermolide analog, an epothilone, actinomycin, an actinomycin analog, and combinations thereof.

27 . The method of claim 26 , wherein the active pharmaceutical ingredient is an ansamycin-derived antineoplastic agent selected from the group consisting of geldanmycin, a geldanmycin derivative and a geldanmycin analog.

28 . The method of claim 26 , wherein the active pharmaceutical ingredient is an epothilone selected from the group consisting of epothilone A, epothilone B (EPO906), deoxyepothilone B, and epothilone B lactam (BMS-247550).

29 . The method of claim 26 , wherein the active pharmaceutical ingredient is a discodermolide analog selected from the group consisting of 2-epi-discodermolide, 2-des-methyldiscodermolide, 5-hydroxymethyldiscoder-molide, 19-des-aminocarbonyldiscodermolide, 9(13)-cyclodiscodermolide, and laulimalide.

30 . The method of claim 26 , wherein the active pharmaceutical ingredient is an actinomycin analog selected from the group consisting of actinomycin A, C, C3 antibiotic complex, F1, F3, and Z complex.

31 . The method of claim 26 , wherein the active pharmaceutical ingredient is discodermolide.

32 . A method for administering a substantially water-insoluble active pharmaceutical ingredient to a mammal comprising preparing a formulation by dissolving an active pharmaceutical ingredient in dimethyl isosorbide and parenterally administering the resulting formulation to a mammal, wherein the active pharmaceutical ingredient is selected from the group consisting of an ansamycin-derived antineoplastic agent, discodermolide, a discodermolide analog, an epothilone, actinomycin, an actinomycin analog, and combinations thereof.

33 . The method of claim 32 , wherein the active pharmaceutical ingredient is an ansamycin-derived antineoplastic agent selected from the group consisting of geldanmycin, a geldanmycin derivative and a geldanmycin analog.

34 . The method of claim 26 , wherein the active pharmaceutical ingredient is an epothilone selected from the group consisting of epothilone A, epothilone B (EPO906), deoxyepothilone B, and epothilone B lactam (BMS-247550).

35 . The method of claim 26 , wherein the active pharmaceutical ingredient is a discodermolide analog selected from the group consisting of 2-epi-discodermolide, 2-des-methyldiscodermolide, 5-hydroxymethyldiscoder-molide, 19-des-aminocarbonyldiscodermolide, 9(13)-cyclodiscodermolide, and laulimalide.

36 . The method of claim 26 , wherein the active pharmaceutical ingredient is an actinomycin analog selected from the group consisting of actinomycin A, C, C3 antibiotic complex, F1, F3, and Z complex.

37 . The method of claim 26 , wherein the active pharmaceutical ingredient is discodermolide.