Freeze-drying process for preparation of bortezomib for injection

Abstract

The invention provides a freeze-drying process for preparation of bortezomib for injection, and according to the process, after subpackage of a bortezomib liquor, freeze-drying is performed, main features of a pre freezing stage comprise two times of annealing, in a sublimation drying stage, drying is kept for 30-40h at -30 DEG C. The bortezomib for injection prepared by the process is not spurted from a bottle, has full and complete appearance, good solubility, qualified clear degree and high safety, and is suitable for industrial production.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a freeze-drying process for preparing bortezomib for injection. Background technique

[0002] Bortezomib (PS-341) is a dipeptidyl boronic acid compound with high efficiency and specific proteasome inhibition. Approved by the FDA for listing, the trade name is The dosage form is freeze-dried powder injection (injection), which is used for the treatment of multiple myeloma and mantle cell lymphoma. Xi'an Janssen Pharmaceutical Co., Ltd. obtained the import registration approval of bortezomib for injection in China in March 2005.

[0003] Bortezomib is poorly soluble in water. The existing preparation methods of bortezomib for injection mostly use tert-butanol to solubilize, but after lyophilization, the preparation needs to be reconstituted with 0.9% sodium chloride injection, which has difficulties in reconstitution and poor clarity. Unqualified question. In addi...

Examples

Embodiment 1

[0036] Embodiment 1 (sample 1)

[0037] The subpackaged bortezomib intermediate medicinal solution is freeze-dried by the following freeze-drying process:

[0038] (1) Pre-freezing stage: evenly put the bottles containing the liquid medicine into the freeze dryer;

[0039] (1.1) Lower the temperature of the plate layer from room temperature to -50°C at a rate of 1.5°C / min, and keep it warm for 2 hours;

[0040] (1.2) Raise the temperature of the plate layer to -12°C at a rate of 1°C / min, and keep it warm for 3 hours;

[0041] (1.3) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 2 hours;

[0042] (1.4) Raise the temperature of the plate layer to -12°C at a rate of 1°C / min, and keep it warm for 3 hours;

[0043] (1.5) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 3 hours;

[0044] (2) Sublimation drying:

[0045] (2.1) After pre-freezing, start vacuuming, control the vacuum degree to 20Pa, and raise the temperatur...

Embodiment 2

[0050] Embodiment 2 (sample 2)

[0051] The subpackaged bortezomib intermediate medicinal solution is freeze-dried by the following freeze-drying process:

[0052] (1) Pre-freezing stage: evenly put the bottles containing the liquid medicine into the freeze dryer;

[0053] (1.1) Lower the temperature of the plate layer from room temperature to -50°C at a rate of 1.5°C / min, and keep it warm for 2 hours;

[0054] (1.2) Heat the plate layer to -10°C at a rate of 1°C / min and keep it warm for 2 hours;

[0055] (1.3) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 2 hours;

[0056] (1.4) Raise the temperature of the plate layer to -10°C at a rate of 1°C / min and keep it warm for 2 hours;

[0057] (1.5) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 3 hours;

[0058] (2) Sublimation drying:

[0059] (2.1) After pre-freezing, start vacuuming, control the vacuum degree to 20Pa, and raise the temperature of the plate layer t...

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a freeze-drying process for preparing bortezomib for injection. Background technique

[0002] Bortezomib (PS-341) is a dipeptidyl boronic acid compound with high efficiency and specific proteasome inhibition. Approved by the FDA for listing, the trade name is The dosage form is freeze-dried powder injection (injection), which is used for the treatment of multiple myeloma and mantle cell lymphoma. Xi'an Janssen Pharmaceutical Co., Ltd. obtained the import registration approval of bortezomib for injection in China in March 2005.

[0003] Bortezomib is poorly soluble in water. The existing preparation methods of bortezomib for injection mostly use tert-butanol to solubilize, but after lyophilization, the preparation needs to be reconstituted with 0.9% sodium chloride injection, which has difficulties in reconstitution and poor clarity. Unqualified question. In addi...

Examples

Embodiment 1

[0036] Embodiment 1 (sample 1)

[0037] The subpackaged bortezomib intermediate medicinal solution is freeze-dried by the following freeze-drying process:

[0038] (1) Pre-freezing stage: evenly put the bottles containing the liquid medicine into the freeze dryer;

[0039] (1.1) Lower the temperature of the plate layer from room temperature to -50°C at a rate of 1.5°C / min, and keep it warm for 2 hours;

[0040] (1.2) Raise the temperature of the plate layer to -12°C at a rate of 1°C / min, and keep it warm for 3 hours;

[0041] (1.3) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 2 hours;

[0042] (1.4) Raise the temperature of the plate layer to -12°C at a rate of 1°C / min, and keep it warm for 3 hours;

[0043] (1.5) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 3 hours;

[0044] (2) Sublimation drying:

[0045] (2.1) After pre-freezing, start vacuuming, control the vacuum degree to 20Pa, and raise the temperatur...

Embodiment 2

[0050] Embodiment 2 (sample 2)

[0051] The subpackaged bortezomib intermediate medicinal solution is freeze-dried by the following freeze-drying process:

[0052] (1) Pre-freezing stage: evenly put the bottles containing the liquid medicine into the freeze dryer;

[0053] (1.1) Lower the temperature of the plate layer from room temperature to -50°C at a rate of 1.5°C / min, and keep it warm for 2 hours;

[0054] (1.2) Heat the plate layer to -10°C at a rate of 1°C / min and keep it warm for 2 hours;

[0055] (1.3) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 2 hours;

[0056] (1.4) Raise the temperature of the plate layer to -10°C at a rate of 1°C / min and keep it warm for 2 hours;

[0057] (1.5) Cool down the plate layer to -50°C at a rate of 1°C / min and keep it warm for 3 hours;

[0058] (2) Sublimation drying:

[0059] (2.1) After pre-freezing, start vacuuming, control the vacuum degree to 20Pa, and raise the temperature of the plate layer t...

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