Preparation method of voriconazole for injection

A technology for voriconazole and injection, which is applied in the field of preparation of voriconazole for injection, which can solve the problems of uneven finished product, long freeze-drying cycle, rough powder cake, etc., and achieve the effects of improving clarity, improving crystal form, and promoting uniformity

Active Publication Date: 2020-09-25
HAINAN LEVTEC PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The present invention overcomes the deficiencies of the prior art, and provides a preparation method of voriconazole for injection, in order to solve the problems of long freeze-drying cycle, uneven finished product and rough powder cake

Method used

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  • Preparation method of voriconazole for injection
  • Preparation method of voriconazole for injection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 1) Preparation: Weigh voriconazole and sulfobutylbetacyclodextrin (SBECD) at a weight ratio of 1:18, add SBECD to an appropriate amount of water, add voriconazole after SBECD is completely dissolved, and continue stirring until completely dissolved and mixed evenly. Obtain a sample containing voriconazole;

[0020] 2) Sterile filtration, half-stoppering for filling: filter the sample to the aseptic filling room with 0.45 μm and 0.22 μm sterile filters, fill in 25ml vials, and half-stopper;

[0021] 3) vacuum freeze drying:

[0022] a. Overcooling: place the subpackaged samples on the partition of the freeze dryer, set the temperature of the partition to 0°C, and keep at this temperature for 4 hours;

[0023] b. Pre-freezing: set the partition temperature to -45°C and keep at this temperature for 3 hours;

[0024] c. Annealing treatment: Raise the temperature of the separator to -10°C, keep it at this temperature for 5h, and then lower it to -45°C and keep it for 4h; ...

Embodiment 2

[0030] 1) Preparation: Weigh voriconazole and SBECD according to a weight ratio of 1:15, add SBECD into water, add voriconazole after SBECD is completely dissolved, and continue stirring until completely dissolved and mixed uniformly to obtain a voriconazole-containing sample;

[0031] 2) Sterile filtration, half-stoppering for filling: filter the sample to the aseptic filling room with 0.45 μm and 0.22 μm sterile filters, fill in 25ml vials, and half-stopper;

[0032] 3) vacuum freeze drying:

[0033] a. Overcooling: place the subpackaged samples on the partition of the freeze dryer, set the temperature of the partition to -5°C, and keep at this temperature for 2 hours;

[0034] b. Pre-freezing: set the partition temperature to -42°C and keep at this temperature for 4 hours;

[0035] c. Annealing treatment: Raise the temperature of the separator to -5°C, keep it at this temperature for 3 hours, and then lower it to -40°C and keep it for 6 hours;

[0036] d. Vacuuming: Turn ...

Embodiment 3

[0041] 1) Preparation: Weigh voriconazole and SBECD according to a weight ratio of 1:16, add SBECD to an appropriate amount of water, add voriconazole after SBECD is completely dissolved, and continue stirring until completely dissolved and mixed evenly to obtain a voriconazole-containing sample;

[0042] 2) Sterile filtration, half-stoppering for filling: filter the sample to the aseptic filling room with 0.45 μm and 0.22 μm sterile filters, fill in 25ml vials, and half-stopper;

[0043] 3) vacuum freeze drying:

[0044] a. Overcooling: place the subpackaged samples on the partition of the freeze dryer, set the temperature of the partition to -4°C, and keep at this temperature for 3 hours;

[0045] b. Pre-freezing: set the partition temperature to -40°C, and keep at this temperature for 6 hours;

[0046] c. Annealing treatment: Raise the temperature of the separator to -8°C, keep it at this temperature for 4 hours, and then lower it to -43°C and keep it for 5 hours;

[0047...

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Abstract

The invention discloses a preparation method of voriconazole for injection. A sample solution containing voriconazole is sublimated to the end point after supercooling, pre-freezing and annealing treatment, and the voriconazole for injection is obtained through desorption drying; sublimation is divided into a first stage and a second stage, wherein the temperature of the first stage is higher thanthat of the second stage, and the pressure of first stage is lower than that of the second stage; and the first stage and the second stage can be conducted under the conditions that vacuum degrees are not higher than 20 Pa and the temperature is not higher than 15 DEG C. Through the adoption of the sublimation way which is performed with high temperature and low pressure at an earlier stage and with low temperature and high pressure at a later stage, heat and mass transfer processes can be improved, the uniformity of crystallization can be promoted, intra assay variance can be avoided, re-dissolution time can be reduced, and the clarity of re-dissolution liquid medicine can be increased; and sublimation efficiency can be enhanced, freeze-drying periods can be shortened, and production costs can be reduced. Through the optimizing of the pre-freezing technology, crystal morphology can be further improved, the comprehensive advantages of products can be enhanced, and therefore, the advantages of clinical medication can be enhanced.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, more specifically, the invention relates to a preparation method of voriconazole for injection. Background technique [0002] The chemical name of voriconazole is (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazole- 1-yl)-2-butanol, whose molecular formula is C 16 h 14 f 2 N 5 O, the molecular weight is 349.3, and the structural formula is: [0003] [0004] Voriconazole for injection, developed by Pfizer, is a broad-spectrum triazole antifungal drug, suitable for the following fungal infections: invasive Aspergillus, candidemia in non-neutropenic patients, fluconazole-resistant Severe invasive infection caused by Candida, severe infection caused by Actinomycetes sp. and Fusarium sp. It is mainly used for the treatment of patients with progressive and potentially life-threatening fungal infections. [0005] The filling volume of voriconazole...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K31/506A61P31/10F26B5/06
CPCA61K9/19A61K9/0019A61K31/506A61P31/10F26B5/06
Inventor 王雅琦张欣阳秀平梁臻黄浩喜苏忠海
Owner HAINAN LEVTEC PHARMA
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