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Preparation method for gemcitabine hydrochloride lyophilized preparation for injection

A technology of gemcitabine hydrochloride and freeze-dried preparations is applied in the field of drug preparation, which can solve the problems of large difference between product temperature and separator temperature, high solution concentration, cracked vials of vials, etc., and achieves high yield, fast reconstitution, Stable quality effect

Active Publication Date: 2012-08-22
湖北一半天制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Prepare gemcitabine hydrochloride for injection according to the conventional method, the concentration of the solution is relatively high, the filling volume is relatively large, the temperature difference between the product temperature and the clapboard temperature is relatively large during pre-freezing, and the cracking and bottoming of the vial are serious.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Taking 100 bottles of gemcitabine hydrochloride freeze-dried preparation for injection as an example, the specific preparation method is:

[0020] Weigh 100.0g of mannitol and 6.3g of sodium acetate, dissolve in 2000ml of water, weigh 113.9g of gemcitabine hydrochloride and add to the solution to dissolve, weigh 2.0g of activated carbon and add to the liquid, stir for 30min, and filter the liquid with two 0.45μm filter membranes Decarburization, then pass the decarburized drug solution through a 0.22μm antibacterial film, measure the pH value, subpackage after the content is qualified, and then freeze-dry at low temperature according to the following procedures:

[0021] Pre-freezing: Cool the product to -45°C and keep it warm for 2 hours.

[0022] Sublimation drying: raise the temperature of the product to -20°C and keep it warm for 30 to 35 hours, then raise the temperature of the product to 0°C and keep it warm for 8 hours;

[0023] Analytical drying: heat the heat ...

Embodiment 2

[0025] Prepare 1.0 g of gemcitabine hydrochloride solution according to conventional methods, then carry out low-temperature freeze-drying according to the following procedures:

[0026] A. Pre-freezing: first cool the gemcitabine hydrochloride solution to -20°C and keep it warm for 1-2 hours. After the temperature of the product drops to -16-20°C, quickly cool it down to -40±2°C and keep it warm for 2-3 hours.

[0027] B. Sublimation drying: vacuumize the box to 7-12 Pa, heat the heat transfer oil at a rate of 1-2 °C / h, keep it warm when the temperature of the heat transfer oil rises to 0 °C, the temperature difference between the sample and the heat transfer oil should be less than 15 ~20±2℃, the total time should not be less than 30h.

[0028] C. Analytical drying: heat the heat transfer oil at a rate of 1°C / 10min, raise the temperature of the product to 40±2°C, and keep it warm for 3 to 5 hours.

Embodiment 3

[0030] Prepare 1.0 g of gemcitabine hydrochloride solution according to conventional methods, then carry out low-temperature freeze-drying according to the following procedures:

[0031] A. Pre-freezing: first cool down the gemcitabine hydrochloride solution to -12°C~-14°C; then lower the heat transfer oil to -20°C at a rate of 1°C / 10min, keep it warm for 2~3 hours, and wait for the temperature of the product to drop to -16~- After 20°C, quickly cool down to -40±2°C and keep warm for 4-5 hours.

[0032] B. Sublimation drying: vacuumize the box to 7-12 Pa, heat the heat transfer oil at a rate of 1-2 °C / h, keep it warm when the temperature of the heat transfer oil rises to 0 °C, the temperature difference between the sample and the heat transfer oil should be less than 15 ~20±2℃, the total time should not be less than 30h.

[0033] C. Analytical drying: heat the heat transfer oil at a rate of 1°C / 10min, raise the temperature of the product to 40±2°C, and keep it warm for 3 to 5...

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Abstract

The invention discloses a preparation method for a gemcitabine hydrochloride lyophilized preparation for injection, comprising the following steps: step A of pre-cooling: reducing temperature of gemcitabine hydrochloride solution to negative 12-negative 14 degrees centigrade at the first, then reducing temperature of a heat transfer oil to negative 20 degrees centigrade at a speed of 1 degree centigrade per 10 minutes, keeping the temperature for 2-3 h, after temperature of products is reduced to negative 16-negative 20 degrees centigrade, fast reducing temperature to negative 38-negative 42 degrees centigrade, and keeping temperature for 4-5 h; step B of sublimating a drying step: vacuumizing to 7-12 Pa in a box body, heating the heat transfer oil at the speed of 1-2 degrees centigrade per hour, when the temperature of the heat transfer oil is increased to 0 degree centigrade, keeping the temperature, wherein total time is not less than 30 h, temperature difference of the sample and the heat transfer oil is less than 22 degrees centigrade; step C of analyzing and drying step: heating the heat transfer oil at the speed of 1 degree centigrade per 10 minutes, increasing the temperature of products to 38-42 degrees centigrade and keeping the temperature for 3-5 h. The lyophilized preparation prepared by the invention is featured with sponginess, reliable quality, fast re-dissolving property and good clarity.

Description

technical field [0001] The invention relates to a preparation method of medicines, in particular to a preparation method of gemcitabine hydrochloride freeze-dried powder injection as an antineoplastic drug. Background technique [0002] Gemcitabine hydrochloride is a new type of synthetic antineoplastic drug, which was approved for marketing in South Africa, Sweden, the Netherlands and other countries in 1995, and was approved for marketing by the US FDA in 1996. [0003] Prepare gemcitabine hydrochloride freeze-dried preparations for injection according to conventional methods. The process steps include pre-freezing, sublimation, and drying. The specific methods are: A. Pre-freezing: first cool the product to -45°C and keep it warm for 2 hours; : Raise the temperature of the product to -20°C, keep it warm for 30-35 hours, then raise the temperature of the product to 0°C and keep it warm for 8 hours, and then raise the temperature of the product to 45°C; C. Analytical drying...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K31/7068A61P35/00
Inventor 易镇海李方芝
Owner 湖北一半天制药有限公司
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