A kind of injection composition containing cabazitaxel and its preparation method

Abstract

The invention provides a Jevtana-containing injection composition and a preparation method thereof. A mass ratio of Jevtana, polysorbate to citric acid in the Jevtana-containing injection composition is 1: 20-30: 0.05-0.25 and a tert-butyl alcohol residual quantity ratio is less than 0.5%. The preparation method utilizes tert-butyl alcohol as a solvent and a mass ratio of Jevtana to tert-butyl alcohol is 1: 20-45. The preparation method comprises the following steps of adding polysorbate-80 and citric acid into tert-butyl alcohol, carrying out stirring for dissolution, adding Jevtana into the solution for dissolution, carrying out sterilization filtration, carrying out split charging and carrying out vacuum removal of tert-butyl alcohol.

Description

technical field

[0001] The invention relates to an injection composition with cabazitaxel as an active ingredient and a preparation method thereof. Background technique

[0002] Cabazitaxel belongs to taxane antineoplastic drugs, which is prepared by semi-synthesis of precursors extracted from Taxus chinensis. The FDA of the United States and the EMA of the European Union successively approved the marketing of this product in June 2010 and March 2011 respectively. It is used in combination with prednisone to treat hormone-refractory metastatic prostate cancer previously treated with docetaxel-containing regimens. Cabazitaxel is white to off-white powder with molecular formula C 45 h 57 NO 14 , molecular weight 835.93, its lipophilicity, insoluble in water, soluble in ethanol, the structural formula is as follows:

[0003]

[0004] Cabazitaxel injection (Jevtana TM ) is a combined package of two vials, one of which contains 1.5ml of concentrated drug solution, and the...

Examples

Embodiment 1

[0037]

[0038] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 20°C to 25°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 130Pa to 150Pa, and maintain it for 4 hours; adjust the pressure of the front box at 10Pa to 20Pa, and keep it for 4 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product...

Embodiment 2

[0040]

[0041] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 25°C to 30°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 50Pa to 80Pa, and maintain it for 4 hours; adjust the pressure of the front box at 30Pa to 50Pa, and keep it for 3 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product. ...

Embodiment 3

[0043]

[0044] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 30°C to 35°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 100Pa to 120Pa, and maintain it for 3 hours; adjust the pressure of the front box at 10Pa to 20Pa, and keep it for 3 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product...

technical field

[0001] The invention relates to an injection composition with cabazitaxel as an active ingredient and a preparation method thereof. Background technique

[0002] Cabazitaxel belongs to taxane antineoplastic drugs, which is prepared by semi-synthesis of precursors extracted from Taxus chinensis. The FDA of the United States and the EMA of the European Union successively approved the marketing of this product in June 2010 and March 2011 respectively. It is used in combination with prednisone to treat hormone-refractory metastatic prostate cancer previously treated with docetaxel-containing regimens. Cabazitaxel is white to off-white powder with molecular formula C 45 h 57 NO 14 , molecular weight 835.93, its lipophilicity, insoluble in water, soluble in ethanol, the structural formula is as follows:

[0003]

[0004] Cabazitaxel injection (Jevtana TM ) is a combined package of two vials, one of which contains 1.5ml of concentrated drug solution, and the...

Examples

Embodiment 1

[0037]

[0038] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 20°C to 25°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 130Pa to 150Pa, and maintain it for 4 hours; adjust the pressure of the front box at 10Pa to 20Pa, and keep it for 4 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product...

Embodiment 2

[0040]

[0041] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 25°C to 30°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 50Pa to 80Pa, and maintain it for 4 hours; adjust the pressure of the front box at 30Pa to 50Pa, and keep it for 3 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product. ...

Embodiment 3

[0043]

[0044] Add the prescribed amount of polysorbate-80 and citric acid to tert-butanol and stir to dissolve, then add the prescribed amount of cabazitaxel, stir until the solution is clear, take the intermediate to test the pH and content, pass through a 0.22μm micropore The filter membrane was sterilized and filtered, and the filtrate was evenly distributed in 10 10ml vials, and half-tightened to a freeze dryer. Control the temperature of the front box of the freeze dryer at 30°C to 35°C, and the temperature of the cold trap at -80°C; turn on the vacuum pump, control the pressure of the front box at 100Pa to 120Pa, and maintain it for 3 hours; adjust the pressure of the front box at 10Pa to 20Pa, and keep it for 3 hours; do not set The front box pressure value, vacuumize, when the pressure is lower than 5Pa, close the septum valve, after the front box pressure has no significant change, fully press the plug, take out the box, tie the cover, and get the finished product...

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