A preparation method of moxifloxacin hydrochloride preparation

Abstract

The invention discloses a preparation method of a moxifloxacin hydrochloride preparation, which comprises adding moxifloxacin hydrochloride into water for injection, stirring until dissolved, adding sodium hydroxide solution to adjust pH value, heating and stirring until dissolved; then adding sodium chloride, and fixing the volume, and sequentially cooling, filling, tamponade, and sterilizing to obtain the moxifloxacin hydrochloride preparation. The invention can reduce the preparation volume, shorten the administration time, and can be directly intravenously injected, thereby reducing the cost.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and in particular to a method for preparing a moxifloxacin hydrochloride preparation. Background Art

[0002] Moxifloxacin hydrochloride is an 8-methoxyfluoroquinolone antibacterial drug, mainly used to treat acute bacterial sinusitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, uncomplicated skin and skin tissue infections, complicated intra-abdominal infections, etc. The currently marketed large-volume injection was developed by Bayer of Germany and was first approved for marketing in the United States on April 30, 2002. The license holder is Bayer Vital GmbH, the manufacturer is Bayer AG, and the trade name is Specifications: 250ml: 0.4g Moxifloxacin and 2.0g Sodium Chloride.

[0003] The existing preparations are large-volume injections, which require a long time for intravenous administration and are difficult to combine with other large-volume injections, thus affecting the clinical compliance of patients. Summary of the invention

[0004] In view of the deficiencies of the prior art, the present invention provides a method for preparing a moxifloxacin hydrochloride preparation, which can reduce the preparation volume and shorten the administration time.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing a moxifloxacin hydrochloride preparation, the method comprising the following steps:

[0007] Step S1: preparing the solution: adding moxifloxacin hydrochloride having a volume concentration of 37 to 43 mg / mL into water for injection accounting for 80% to 95% of the total volume of the injection solution, and stirring at room temperature until dissolved;

[0008] Step S2: adding sodium hydroxide solution to the solution obtained in step S1, stirring at 50-60° C. until dissolved for later use;

[0009] Step S3: adding sodium chloride having a volume concentration of 8.5 to 9.5 mg / mL to the solution obtained in step S2, and adjusting the volume to the formula amount, and then cooling the solution for standby use;

[0010] Step S4: filling and sterilization: filling the solution obtained in step S3 into a vial with a volume of 10.2-11.0 mL, plugging and capping, and sterilizing to obtain a moxifloxacin hydrochloride preparation.

[0011] Furthermore, the concentration of moxifloxacin hydrochloride in step S1 is preferably 40 mg / ml.

[0012] Furthermore, the amount of water for injection in step S1 is preferably 90% of the total volume of the injection solution.

[0013] Furthermore, the sodium chloride concentration in step S3 is preferably 9 mg / ml.

[0014] Furthermore, the liquid preparation temperature in step S2 is preferably 60°C.

[0015] Furthermore, the molar concentration of the sodium hydroxide solution in step S2 is 1 mol / L.

[0016] Furthermore, in step S2, the pH of the sodium hydroxide solution is adjusted to a range of 7.5 to 8.5, preferably a pH of 8.

[0017] Furthermore, in step S4, the sterilization condition maintains the temperature at 121° C. to 124° C. for 12 to 15 minutes, preferably maintaining the temperature at 121° C. for 15 minutes.

[0018] Furthermore, the cooling temperature in step S2 is 25°C.

[0019] Furthermore, the stirring speed of step S1 is 300 rpm.

[0020] Furthermore, the filling volume in step S2 is preferably 10.6 mL.

[0021] Compared with the prior art, the advantages of the present invention are:

[0022] 1. Compared with the prior art, the present invention adjusts the osmotic pressure by adding sodium chloride and adjusts the pH of the solution by adding sodium hydroxide to obtain a small-volume moxifloxacin hydrochloride injection. The injection increases the administration method and compatibility method while maintaining the product quality unchanged, thereby improving patient compliance.

[0023] 2. Reducing the volume of the preparation can meet the requirements of compatibility with other large-volume injections, and can also be directly injected intravenously alone, shortening the administration time and improving patient compliance. In addition, small-volume injections are easy to transport and store, reducing costs.

[0024] 3. The preparation method is simple, and the reagents used are pollution-free, reducing harm to the environment. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the embodiments, so that those skilled in the art can fully understand the technical content of the present invention. It should be understood that the following examples are used to further illustrate the present invention and cannot be interpreted as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art according to the above content of the present invention belong to the scope of protection of the present invention. The following examples of specific preparation method parameters are also only an example in a suitable range, that is, those skilled in the art can make a selection within a suitable range according to the description herein, and are not limited to the specific numerical values ​​​​exemplified below.

[0026] A method for preparing a moxifloxacin hydrochloride preparation, the method comprising the following steps:

[0027] Step S1: preparing the solution: adding moxifloxacin hydrochloride having a volume concentration of 37 to 43 mg / mL into water for injection accounting for 80% to 95% of the total volume of the injection solution, and stirring at room temperature until dissolved;

[0028] Step S2: adding sodium hydroxide solution to the solution obtained in step S1, stirring at 50-60° C. until dissolved for later use;

[0029] Step S3: adding sodium chloride having a volume concentration of 8.5 to 9.5 mg / mL to the solution obtained in step S2, and adjusting the volume to the formula amount, and then cooling the solution for standby use;

[0030] Step S4: filling and sterilization: filling the solution obtained in step S3 into a vial with a volume of 10.2-11.0 mL, plugging and capping, and sterilizing to obtain a moxifloxacin hydrochloride preparation.

[0031] The concentration of moxifloxacin hydrochloride in step S1 is 40 mg / ml.

[0032] The amount of water for injection in step S1 is preferably 90% of the total volume of the injection solution.

[0033] The sodium chloride concentration in step S2 is preferably 9 mg / ml.

[0034] The liquid preparation temperature in step S1 is preferably 60°C.

[0035] The molar concentration of the sodium hydroxide solution in step S1 is 1 mol / L.

[0036] In step S1, the pH of the sodium hydroxide solution is adjusted to a range of 7.5 to 8.5, preferably 8.

[0037] In step S2, the sterilization condition is to maintain the temperature at 121° C. to 124° C. for 12-15 minutes, preferably at 121° C. for 15 minutes.

[0038] The cooling temperature in step S2 is 25°C.

[0039] The stirring speed in step S1 is 300 rpm.

[0040] The filling volume in step S2 is preferably 10.6 mL.

[0041] The present invention adjusts the osmotic pressure by adding sodium chloride and adjusts the pH value of the solution by adding sodium hydroxide to obtain a small-volume moxifloxacin hydrochloride injection. The injection increases the administration mode and the compatibility mode while maintaining the product quality unchanged, thereby improving the patient compliance.

[0042] Reducing the volume of the preparation can meet the requirements of compatibility with other large-volume injections, and can also be injected directly intravenously alone, shortening the administration time and improving patient compliance. In addition, small-volume injections are easy to transport and store, reducing costs.

[0043] The following is combined with specific embodiments to further illustrate and describe the concept of the present invention, but it does not mean that the present invention is limited to the specific scheme described below. In the embodiments, any specific numerical value within the scope of the present invention is applicable.

[0044] Embodiment 1:

[0045] Prescription: Moxifloxacin hydrochloride (calculated as moxifloxacin) 4.0g, sodium chloride 0.8g, water for injection 90mL, appropriate amount of pH adjuster (sodium hydroxide), filling specification 10.8mL / bottle.

[0046] Step S1: Add 4.0 g of moxifloxacin hydrochloride to 90 mL of water and stir at 300 rpm at room temperature until dissolved;

[0047] Step S2: adjust the pH of the solution obtained in step S1 to 7.9-8.1 using 1 mol / L sodium hydroxide, raise the temperature to 60°C and stir at 300 rpm using a magnetic stirrer until completely dissolved;

[0048] Step S3: Add 0.8 g of sodium chloride to the solution obtained in step S2, stir until dissolved, and adjust the volume to 100 mL, then cool to 25° C. for later use;

[0049] Step S4: filling and sterilization: the solution obtained in step S3 is filled into each bottle at 10.8 mL, plugged and capped, and sterilized at a temperature of 121° C. for 15 min to obtain a moxifloxacin hydrochloride preparation.

[0050] The results are shown in Table 1. Moxifloxacin hydrochloride was completely dissolved in 17 seconds, and the obtained moxifloxacin hydrochloride preparation had high purity and few impurities.

[0051] Embodiment 2:

[0052] Prescription: Moxifloxacin hydrochloride (calculated as moxifloxacin) 4.0g, sodium chloride 0.9g, water for injection 90mL, appropriate amount of pH adjuster (sodium hydroxide), filling specification 10.8mL / bottle.

[0053] Step S1: Add 4.0 g of moxifloxacin hydrochloride to 90 mL of water and stir at 300 rpm at room temperature until dissolved;

[0054] Step S2: adjust the pH of the solution obtained in step S1 to 7.9-8.1 using 1 mol / L sodium hydroxide, raise the temperature to 60°C and stir at 300 rpm using a magnetic stirrer until completely dissolved;

[0055] Step S3: Add 0.9 g of sodium chloride to the solution obtained in step S2, stir until dissolved, and adjust the volume to 100 mL, then cool to 25° C. for later use;

[0056] Step S4: filling and sterilization: the solution obtained in step S3 is filled into each bottle at a rate of 10.8 mL, the bottle is plugged and capped, and sterilized at a temperature of 121° C. for 15 min to obtain a floxacin hydrochloride preparation.

[0057] The results are shown in Table 1. Moxifloxacin hydrochloride was completely dissolved in 15 seconds, and the obtained moxifloxacin hydrochloride preparation had high purity and few impurities.

[0058] Comparative Example 2-1:

[0059] Prescription: Moxifloxacin hydrochloride (calculated as moxifloxacin) 4.0g, sodium chloride 0.8g, water for injection 90mL, appropriate amount of pH adjuster (sodium hydroxide), filling specification 10.8mL / bottle.

[0060] Step S1: Add 0.9 g of sodium chloride to 90 mL of water, heat to 60 °C and stir at 300 rpm using a magnetic stirrer until completely dissolved;

[0061] Step S2: Add 4.0 g of moxifloxacin hydrochloride to the solution of step S1 and stir at 300 rpm at room temperature until dissolved for later use;

[0062] Step S3: Use 1 mol / L sodium hydroxide to adjust the pH of the solution obtained in step S2 to 7.9-8.1, stir until dissolved, and adjust the volume to 100 mL, and then cool to 25° C. for use;

[0063] Step S4: filling and sterilization: the solution obtained in step S3 is filled into each bottle at a rate of 10.8 mL, the bottle is plugged and capped, and sterilized at a temperature of 121° C. for 15 min to obtain a moxifloxacin hydrochloride preparation.

[0064] The results are shown in Table 1. Comparative Example 2-1 changes the order of adding moxifloxacin hydrochloride and sodium chloride compared to Example 2. It can be seen that moxifloxacin hydrochloride is completely dissolved in 5 minutes and 49 seconds, and the prolonged preparation time affects the stability of the product.

[0065] Table 1 Test data of Example 1 to Comparative Example 2-1

[0066]

[0067] Combining the above table, we can see

[0068] 1. Combining Example 1 and Example 2, it can be seen that moxifloxacin hydrochloride is completely dissolved in 15 to 17 seconds, the preparation time is short, the content is stable between products, the content of related substances is low, the content of related substances is basically unchanged, it has good stability, high effectiveness and safety, and is suitable for direct intravenous drip in the human body.

[0069] 2. Comparative Example 2-1, in which sodium chloride is dissolved first and then moxifloxacin hydrochloride is dissolved and the pH is adjusted, it can be seen that the dissolution time of moxifloxacin hydrochloride is relatively long, which has the risk of affecting product quality. Meanwhile, the longer production time increases the production cost.

[0070] 3. Based on the above, it is further explained that the present invention first dissolves moxifloxacin hydrochloride, then uses it in combination with a pH regulator, and finally adds sodium chloride to dissolve it, which can effectively ensure the stability of product quality, so that the moxifloxacin hydrochloride preparation has a short preparation time, stable product quality, and low content of related substances, thereby ensuring the effectiveness and safety of the medication.

[0071] It should be pointed out that the above preferred embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a moxifloxacin hydrochloride preparation, characterized in that: The method comprises the following steps: Step S1: preparing the solution: adding moxifloxacin hydrochloride having a volume concentration of 37 to 43 mg / mL into 80% to 95% of the total volume of the injection solution in water for injection, and stirring at 300 rpm at room temperature until dissolved; Step S2: adding a sodium hydroxide solution with a molar concentration of 1 mol / L to the solution obtained in step S1 to adjust the pH range to 7.5-8.5, stirring at 50-60° C. with a magnetic stirrer at 300 rpm until dissolved for later use; Step S3: adding sodium chloride with a volume concentration of 8.5-9.5 mg / mL to the solution obtained in step S2, and adjusting the volume to the total volume of the injection solution, and then cooling the solution to 25° C. for standby use; Step S4: filling and sterilization: filling the solution obtained in step S3 into a vial with a volume of 10.2-11.0 mL, plugging and capping, and sterilizing to obtain a moxifloxacin hydrochloride preparation, wherein the sterilization condition maintains a temperature of 121° C. to 124° C. for 12 to 15 min.

2. The method for preparing the moxifloxacin hydrochloride preparation according to claim 1, characterized in that: The concentration of moxifloxacin hydrochloride in step S1 is 40 mg / mL.

3. The method for preparing the moxifloxacin hydrochloride preparation according to claim 1 or 2, characterized in that: The amount of water for injection in step S1 is 90% of the total volume of the injection solution.

4. The method for preparing the moxifloxacin hydrochloride preparation according to claim 1, characterized in that: The sodium chloride concentration in step S3 is 9 mg / mL.

5. The method for preparing the moxifloxacin hydrochloride preparation according to claim 1, characterized in that: The reaction temperature of step S2 is 60°C.

6. The method for preparing the moxifloxacin hydrochloride preparation according to claim 1, characterized in that: In the step S4, the solution obtained in step S3 is filled into each bottle at 10.8 mL.

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