Low oil emulsion compositions for delivering taxoids and other insoluble drugs

1. A sterile injectable oil-in-water emulsion comprising:

(a) paclitaxel at a concentration selected from the group consisting of 0.03%, 0.04%, and 0.05% by weight,

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof,

(c) a phospholipid component at a concentration from 1% to 4% by weight, wherein the weight ratio of the oil component to the phospholipid component is about 1:1,

(d) sodium hydroxide and/or hydrochloric acid to adjust the pH to between about 6 and 7, and

(e) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

2. The injectable emulsion of claim 1 wherein paclitaxel is at a concentration of about 0.05% by weight.

3. The injectable emulsion of claim 1 wherein the vegetable oil is soybean oil.

4. The injectable emulsion of claim 1 wherein the phospholipid component comprises soy lecithin or egg lecithin.

5. The injectable emulsion of claim 1 further comprising a stabilizer.

6. The injectable emulsion of claim 5 wherein the stabilizer is ethylene diamine-tetraacetic acid (EDTA).

7. The injectable emulsion of claim 6 wherein the concentration of EDTA is from about 0.001% to about 0.01% by weight.

8. The injectable emulsion of claim 1 further comprising a tonicity modifier.

9. The injectable emulsion of claim 1 wherein the average size of the oil droplets in the emulsion does not increase more than 25% after storage at about 2-8° C. for 6 months.

10. The injectable emulsion of claim 1 wherein the concentration of paclitaxel in the emulsion does not decrease by more than 10% after storage at about 2-8° C. for 6 months.

11. A sterile injectable oil-in-water emulsion comprising:

(a) docetaxel at a concentration selected from the group consisting of 0.03%, 0.04% and 0.05% by weight,

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof,

(c) a phospholipid component at a concentration from 1% to 4% by weight, wherein the ratio of the oil component to the phospholipid component is about 1:1, and

(d) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

12. The injectable emulsion of claim 11 further comprising:

(a) docetaxel at a concentration of 0.05% by weight,

(b) the medium chain triglyceride at a concentration from 1% to 3% by weight,

(c) the vegetable oil is soybean oil at a concentration from 1% to 3% by weight,

(d) the phospholipid component is soy lecithin or egg lecithin at a concentration from 1% to 5% by weight, and

(e) optionally EDTA at a concentration of 0.005% by weight.

13. A sterile injectable oil-in-water emulsion consisting essentially of:

(a) paclitaxel at a concentration selected from the group consisting of 0.03%, 0.04% and 0.05% by weight;

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof;

(c) a phospholipid component at a concentration from 1% to 4% by weight, wherein the weight ratio of the oil component to the phospholipid component is about 1:1;

(d) sodium hydroxide and/or hydrochloric acid to adjust the pH to between about 6 and 7, and

(e) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

14. The injectable emulsion of claim 13 , wherein paclitaxel is at a concentration of about 0.05% by weight.

15. The injectable emulsion of claim 13 , wherein the vegetable oil is soybean oil.

16. The injectable emulsion of claim 13 , wherein the phospholipid component comprises soy lecithin or egg lecithin.

17. A sterile injectable oil-in-water emulsion consisting essentially of:

(a) paclitaxel at a concentration selected from the group consisting of 0.03%, 0.04% and 0.05% by weight;

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof;

(c) a phospholipid component at a concentration from 1% 4% by weight, wherein the weight ratio of the oil component to the phospholipid component is about 1:1;

(d) sodium hydroxide and/or hydrochloric acid to adjust the pH to between about 6 and 7;

(e) a stabilizer; and

(f) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

18. The injectable emulsion of claim 17 , wherein the stabilizer is ethylene diamine-tetraacetic acid (EDTA).

19. The injectable emulsion of claim 18 , wherein the concentration of EDTA is from about 0.001% to about 0.01% by weight.

20. A sterile injectable oil-in-water emulsion consisting essentially of:

(a) paclitaxel at a concentration selected from the group consisting of 0.03%, 0.04% and 0.05% by weight;

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof;

(c) a phospholipid component at a concentration from 1% to 4% by weight, wherein the weight ratio of the oil component to the phospholipid component is about 1:1;

(d) sodium hydroxide and/or hydrochloric acid to adjust the pH to between about 6 and 7;

(e) a tonicity modifier; and

(f) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

21. The injectable emulsion of claim 13 , wherein the average size of the oil droplets in the emulsion does not increase more than 25% after storage at about 2-8° C. for 6 months.

22. The injectable emulsion of claim 13 , wherein the concentration of paclitaxel in the emulsion does not decrease by more than 10% after storage at about 2-8° C. for 6 months.

23. A sterile injectable oil-in-water emulsion consisting essentially of:

(a) docetaxel at a concentration selected from the group consisting of 0.03%, 0.04% and 0.05% by weight,

(b) an oil component at a concentration from 1% to 4% by weight, wherein the oil component comprises a vegetable oil or a medium chain triglyceride, or a mixture thereof,

(c) a phospholipid component at a concentration from 1% to 4% by weight, wherein the ratio of the oil component to the phospholipid component is about 1:1, and

(d) water, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.

24. A sterile injectable oil-in-water emulsion consisting essentially of:

(a) docetaxel at a concentration of 0.05% by weight,

(b) an oil component at a concentration from 1% to 3% by weight, wherein the oil component is a medium chain triglyceride;

(c) a phospholipid component at a concentration from 1% to 4% weight, wherein the ratio of the oil component to the phospholipid component is about 1:1, wherein the phospholipid component is soy lecithin or egg lecithin;

(d) water; and

(e) optionally EDTA at a concentration of about 0.005% by weight, wherein said injectable oil-in-water emulsion has an average oil droplet diameter in a range of 75 nm to 150 nm, is sterilized by filtration using a 0.2 μm filter, does not include a cryoprotectant or protein, and is stable for at least 18 months.