Non-Aqueous Taxane Pro-Emulsion Formulations and Methods of Making and Using the Same

A. Working Example 1

Lot. 16

[0058]150 mg of docletaxel, 150 mg of MCT, 5 g of polysorbate 80, and 3.5 g of propylene glycol were placed into a 200 ml beaker. The beaker was heated to 50° C. and the ingredients dissolved almost completely in an ultrasonic disperser. The beaker was placed in a water bath with the temperature setting at 60° C. The contents were then agitated with a high-speed mixer (7,000 rpm×2 min.) while adding about 35 ml of warm water at 60° C. The contents were then agitated more (10,000 rpm×5 min.) to get a uniform solution.

[0059]2.5 g of propylene glycol were added to this uniform solution. The solution was then gently stirred for more uniformity and sufficient pure water was added to make the volume 50 ml. The pH of this solution was adjusted to 4 with 1N hydrochloric acid or 0.1 N hydrochloric acid.

[0060]This solution was poured into each 50 ml vial tube while applying nitrogen and the tube was sealed. High-pressure steam sterilization (121° C.×10 min.) was then a

C. Working Example 2

Lot. 33

[0063]400 mg of docetaxel trihydrate, 400 mg of MCT, 9.5 g of polysorbate 80, 7 g of polyethylene glycol 300 (average molecule weight=300) and 100 mg of lactic acid mixture (=80 mg of lactic acid and 20 mg of 70% sodium lactate) were placed into a 50 ml beaker. The beaker was heated to 50° C. and the ingredients were almost completely dissolved in an ultrasonic disperser

[0064]The resultant solution was poured into a 5 ml vial tube through a 0.2μ filter while applying nitrogen and the tube was sealed. Steam treatment (95° C.×30 min.) was then applied.

[0065]174 mg of the resultant non-aqueous composition was then placed into a test tube. 25 ml of 5% glucose solution were added and the tube was shaken by hand for about 20 seconds to obtain a clear solution. When the particle size was measured via a particle size distribution in the dynamic light scattering measurement protocol, the average size was observed to be 19.4 nm.

D. Additional Working Examples

[0066]Additional formulations and the above formulation are summarized below in Table 4:

TABLE 4Lot.31323334Drug [mg]DOC 4DOC-3W 4DOC-3W 4DOC-3W 4Oil [mg]MCT 4MCT 4MCT 4MCT 4Surfactant [mg]Polysorbate 100Polysorbate 95Polysorbate 95Polysorbate 95Non AqueousPEG300 40PEG300 85PEG300 70PEG300 70solvent [mg]PEG400 10Lactic acid1111mixture [mg]Heated treatment95° C. × 30 min.95° C. × 30 min.95° C. × 30 min.No treatmentDOC-3W—docetaxel trihydrate