Isoproterenol hydrochloride injection and preparation process thereof

A technology of isoproterenol hydrochloride and injection, which is applied in drug delivery, cardiovascular system diseases, drug combination, etc., can solve the problems of high prescription cost and unachievable preparation method, and achieve the effect of low cost of prescription and preparation process

Inactive Publication Date: 2012-07-04

上海禾丰制药有限公司

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AI-Extracted Technical Summary

Problems solved by technology

[0005] The cost of the existing prescription is relatively high, and...

Abstract

The invention discloses a formula of isoproterenol hydrochloride injection and a preparation process thereof. The isoproterenol hydrochloride injection contains, per 1000 mL, 5 g of isoproterenol hydrochloride, 60 g to 110 g of sodium chloride, 1 g to 5 g of disodium ethylenediaminetetraacetate (EDTA-2Na), and water for injection added up to 1000 mL. The quality of the isoproterenol hydrochloride injection conforms to the regulations of notice on issue of chemical injection and multi-component biochemical injection basic technical requirements ([2008] No.7 file) issued by State Food and Drug Administration in 2008 and the quality standards of China pharmacopoeia (part II, 2010 edition).

Application Domain

Organic active ingredientsPharmaceutical delivery mechanism +1

Technology Topic

Disodium EdetateInjection solution +11

Image

Examples

Experimental program(4)

Example Embodiment

[0045] Example 1

[0046] Isoproterenol Hydrochloride Injection, contains the following ingredients:

[0047] Each 10000ml injection contains,

[0048] Isoproterenol Hydrochloride 5g

[0049] Sodium Chloride 85g

[0050] Sodium metabisulfite 10g

[0051] Disodium Edetate 3g

[0052] Water for injection was added to 10000ml.

[0053] Its preparation process is:

[0054] (1) Add 90% of the total volume of water for injection to the preparation container, cool it to below 30 °C, and pass CO 2 15 minutes to saturate;

[0055] (2) Dissolve disodium edetate with hot water for injection at 80°C to 85°C and set aside for use;

[0056] (3) Start the stirrer, add sodium chloride, sodium metabisulfite, isoproterenol hydrochloride and disodium edetate solution obtained in step (2) to the water for injection obtained in step (1) in turn, stir for 5 minutes to dissolve ;

[0057] (4) Adjust the pH value of the solution obtained in step (3) with 10% hydrochloric acid or 5% sodium hydroxide to make the pH value reach 2.3 to 4.3, add water for injection to the total amount, and stir for 10 minutes until uniform;

[0058] (5) Filter the solution obtained in step (4) with a 0.45μm, 0.22μm pleated filter until it becomes clear;

[0059] (6) The solution obtained in step (5) is potted according to the potting operation procedure, and the ampoule is filled with N during potting. 2;

[0060] (7) Sterilize at 100°C for 30 minutes, or sterilize at 121°C for 12 minutes.

[0061] According to the quality standard requirements for isoproterenol hydrochloride injection in Part II of the Chinese Pharmacopoeia 2010 edition, the stability of the two samples prepared under the sterilization conditions of 100°C for 30 minutes and 121°C for 12 minutes were investigated and tested, respectively. The results are compared as follows:

[0062]

[0063] In this formulation, sodium metabisulfite acts as an antioxidant to prevent the oxidation of isoproterenol hydrochloride. However, because sodium metabisulfite easily reacts with isoproterenol hydrochloride to produce sulfonated compounds, and the samples after sterilization at 121 °C for 12 minutes cannot make the sulfonated compounds reach the quality standard of isoproterenol hydrochloride injection in the second part of the Chinese Pharmacopoeia 2010 edition.

[0064] Therefore, we revised the formulation process of isoproterenol hydrochloride injection, mainly focusing on the screening of antioxidants, and then sterilized according to the sterilization process of 121 ° C for 12 minutes, and the prepared samples were tested again. Data are as follows:

[0065]

[0066] Through the above tests, we can find that removing the antioxidants anhydrous sodium sulfite or sodium metabisulfite in isoproterenol hydrochloride injection can avoid the production of sulfonates, isoproterenol hydrochloride injection can be sterilized at 121 ℃ for 12 minutes Terminal sterilization process, all inspection items are in compliance with regulations, and SAL ≤ 10 can be guaranteed -6 , and F 0 ≥12; and the use of aseptic production technology is also applicable, which can meet the SAL not greater than 10 -3 technical requirements. However, due to the easy oxidation of epinephrine injections, the production process needs to be improved, and the N 2.

Example Embodiment

[0067] Example 2

[0068] Isoproterenol Hydrochloride Injection, contains the following ingredients:

[0069] Each 10000ml injection contains,

[0070] Isoproterenol Hydrochloride 5g

[0071] Sodium Chloride 60g

[0072] Disodium Edetate 1g

[0073] Water for injection was added to 10000ml.

[0074] The preparation process of described isoproterenol hydrochloride injection, comprises the following steps:

[0075] (1) Add 90% of the total volume of water for injection to the preparation container, cool it to below 30 °C, and pass CO 2 15 minutes to saturate;

[0076] (2) Dissolve disodium edetate with hot water for injection at 80°C to 85°C and set aside for use;

[0077] (3) Start the stirrer, add sodium chloride, isoproterenol hydrochloride and disodium edetate solution obtained in step (2) to the water for injection obtained in step (1) in turn, and stir for 5 minutes to dissolve;

[0078] (4) Adjust the pH value of the solution obtained in step (3) with 10% hydrochloric acid or 5% sodium hydroxide to make the pH value reach 2.3 to 4.3, add water for injection to the total amount, and stir for 10 minutes until uniform;

[0079] (5) Filter the solution obtained in step (4) with a 0.45μm, 0.22μm pleated filter element until it becomes clear, and during the filtration process, the solution tank is filled with N 2;

[0080] (6) The solution obtained in step (5) is potted according to the potting operation procedure, and the ampoule is filled with N during potting. 2;

[0081] (7) Sterilize at 100°C for 30 minutes, or sterilize at 121°C for 12 minutes.

[0082] Of course, steps (1) to (4) in the above formulation process can also be prepared by aseptic production, and then the solution obtained by filtration at 0.45 μm and 0.22 μm is clarified. N 2 , and then perform aseptic potting. When potting, the ampoule is filled with N. 2.

[0083] Quality inspection is carried out to the prepared isoproterenol hydrochloride injection, and the results are as follows:

[0084]

[0085] Compared with Example 1, the production process of the present invention is carried out in a closed environment, and is filtered and potted by continuously passing N 2 The product is sealed and protected to ensure that the raw material "isoproterenol hydrochloride" is not oxidized, thereby achieving the purpose of removing the antioxidant "sodium metabisulfite" from the prescription.

Example Embodiment

[0086] Example 3

[0087] Isoproterenol Hydrochloride Injection, contains the following ingredients:

[0088] Each 10000ml injection contains,

[0089] Isoproterenol Hydrochloride 5g

[0090] Sodium Chloride 85g

[0091] Disodium Edetate 3g

[0092] Water for injection was added to 10000ml.

[0093] The preparation process is the same as that of Example 2.

[0094] Quality inspection is carried out to the prepared isoproterenol hydrochloride injection, and the results are as follows:

[0095]

PUM

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