A preparation method of nicardipine hydrochloride injection

Abstract

The application provides a preparation method of nicardipine hydrochloride injection. The preparation method grinds nicardipine hydrochloride and a polyhydric alcohol according to a specific ratio to prepare a solid dispersion, dissolves the solid dispersion in water for injection at a temperature of not higher than 35 DEG C, and adjusts the pH value of the solution to be acidic by using a pH regulator. The preparation method greatly improves the dissolution speed of nicardipine hydrochloride, reduces the generation of impurities in the preparation and storage processes, avoids the use of activated carbon for decolorization, and is simple and feasible.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and relates to a method for preparing nicardipine hydrochloride injection. Background Technology

[0002] Nicardipine hydrochloride, also known as noratentan hydrochloride, is a second-generation dihydropyridine calcium channel blocker. Its chemical name is 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylic acid 2-[methyl(benzyl)amino]ethylmethyl ester hydrochloride. Nicardipine hydrochloride blocks the influx of calcium ions into vascular smooth muscle cells, thereby dilating blood vessels and lowering blood pressure. Its effect on vascular smooth muscle is 30,000 times stronger than its effect on the myocardium, and its vascular selectivity is significantly higher than other calcium channel blockers. Clinically, it is widely used in the treatment of hypertension and angina pectoris and is one of the first-line drugs for antihypertensive treatment.

[0003] Nicardipine hydrochloride formulations include nicardipine hydrochloride tablets, nicardipine hydrochloride injection, nicardipine hydrochloride sodium chloride injection, and nicardipine hydrochloride glucose injection. Nicardipine hydrochloride injection is clinically used for the emergency treatment of abnormal hypertension during surgery and for hypertensive emergencies. This drug was first successfully developed by Yamanouchi Pharmaceutical Co., Ltd. of Japan in the 1980s. The U.S. Food and Drug Administration approved the drug for marketing in January 1992. Shenyang Yamanouchi Pharmaceutical (China) Co., Ltd. manufactures this drug and sells it in China under the brand name "Per".

[0004] Because nicardipine hydrochloride is almost insoluble in water, some literature reports that 100 mg of nicardipine hydrochloride cannot be completely dissolved in 100 ml of water at room temperature, but it can be completely dissolved in 100 ml of hot water. After cooling and placing the solution in a refrigerator overnight, no crystals precipitate. Furthermore, the solution only becomes clear and transparent when the pH value is below 5.0. Therefore, current preparation methods often involve increasing the temperature of the water for injection to ensure complete dissolution of nicardipine hydrochloride in water or excipient solution, and then using a pH adjuster to adjust the pH value to acidic. However, nicardipine hydrochloride is sensitive to high temperatures. Increasing the preparation temperature not only reduces the nicardipine hydrochloride content and increases the impurity content in the solution, but also causes the solution to darken in color. This necessitates the use of activated carbon to decolorize the darkened solution to meet usage requirements. However, the draft for comments on the consistency evaluation of injectable drugs released by the CDE in December 2017 recommends against the use of activated carbon in the production of injectable drugs. The reason is that activated carbon has a certain adsorption effect on the active ingredients in the medicine solution and can also cause some pollution to the product, which can affect the safety and efficacy of the medicine. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a method for preparing nicardipine hydrochloride injection.

[0006] This preparation method involves grinding nicardipine hydrochloride and a polyhydroxy alcohol in a specific ratio to form a solid dispersion, dissolving it in water for injection at a temperature not exceeding 35°C, and then adjusting the pH of the solution to acidic using a pH adjuster. This preparation method significantly improves the dissolution rate of nicardipine hydrochloride, reduces the generation of impurities during preparation and storage, avoids the need for decolorization using activated carbon, and is simple and feasible.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0008] This invention provides a method for preparing nicardipine hydrochloride injection, comprising the following steps:

[0009] Step 1: Nicardipine hydrochloride and solid polyhydroxy alcohol are ground in a specific ratio to prepare a solid dispersion; the mass ratio of nicardipine hydrochloride to polyhydroxy alcohol is 1:20 to 1:50.

[0010] Step 2: Add the solid dispersion obtained in Step 1 to 80% to 90% of the prescribed amount of water for injection, stir to dissolve, and obtain drug solution 1. The temperature of the water for injection is 18 to 35°C.

[0011] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.0-5.0 with acid solution, and add the remaining amount of water for injection to obtain drug solution 2;

[0012] Step 4: Filter the drug solution 2 obtained in Step 3, fill it with nitrogen, seal it, and sterilize it to obtain the finished product of nicardipine hydrochloride injection; the concentration of nicardipine hydrochloride is 0.1% to 0.6% W / V, and the concentration of polyhydroxy alcohol is 2% to 5% W / V.

[0013] This invention first prepares nicardipine hydrochloride and polyhydroxy alcohol into a solid dispersion by grinding, and then dissolves it in water for injection. This significantly improves the dissolution rate of nicardipine hydrochloride and shortens the dissolution time of nicardipine hydrochloride in water for injection. It can avoid the darkening of the color of the resulting injection solution and the generation of impurities caused by dissolving in water for injection at excessively high temperatures.

[0014] According to an embodiment of the present invention, the polyhydroxy alcohol in step one includes one or more of sorbitol, mannitol, xylitol, and inositol.

[0015] According to an embodiment of the present invention, the grinding in step one is not limited to any particular grinding method; it can be done manually or using an electric grinder. The grinding time is not limited; the endpoint is determined by the DSC and X-ray powder diffraction patterns of the ground sample.

[0016] According to an embodiment of the present invention, the temperature of the water for injection in step two is 18-26°C. This temperature range is the optimal temperature condition that allows the dissolution rate of nicardipine hydrochloride, the color of the resulting injection solution, and the content of impurities in the injection solution to all achieve satisfactory results.

[0017] According to an embodiment of the present invention, the pH value of the acid solution in step three is adjusted to 3.1 to 3.5.

[0018] According to an embodiment of the present invention, the acid solution in step three includes one or more of hydrochloric acid, acetic acid, and citric acid.

[0019] According to an embodiment of the present invention, in the nicardipine hydrochloride injection in step four, the concentration of nicardipine hydrochloride is 0.1% W / V; and the concentration of polyhydroxy alcohol is 5% W / V.

[0020] According to an embodiment of the present invention, the filtration in step four is performed using one or more filter membranes with a pore size of 0.22 μm.

[0021] According to an embodiment of the present invention, the nitrogen filling in step four is to ensure that the headspace residual oxygen content of the injection solution after filling is not higher than 2%, so as to reduce impurities generated during storage.

[0022] According to an embodiment of the present invention, the sterilization temperature in step four is 121°C and the sterilization time is 12-15 minutes. To ensure the sterility of the product, sterilization for 15 minutes is preferred.

[0023] One preferred embodiment of the present invention:

[0024] Step 1: Grind 0.1% w / v nicardipine hydrochloride and 5% w / v sorbitol together to prepare a solid dispersion;

[0025] Step 2: Add the solid dispersion obtained in Step 1 to 80%-90% of the prescribed amount of water for injection, wherein the temperature of the water for injection is 18-26℃, stir to dissolve, and obtain drug solution 1;

[0026] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to the prescribed volume to obtain drug solution 2;

[0027] Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0028] Second preferred embodiment of the present invention:

[0029] Step 1: Grind 0.1% w / v nicardipine hydrochloride and 2% w / v sorbitol together to prepare a solid dispersion;

[0030] Step 2: Add the solid dispersion obtained in Step 1 to 80%-90% of the prescribed amount of water for injection, wherein the temperature of the water for injection is 18-26℃, stir to dissolve, and obtain drug solution 1;

[0031] Step 3: Add 3% w / v sorbitol to solution 1 from step 2, stir to dissolve, and obtain solution 2;

[0032] Step 4: Adjust the pH of the drug solution obtained in Step 3 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to the prescribed volume to obtain drug solution 3;

[0033] Step 5: Filter the drug solution 3 obtained in Step 4 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0034] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention provides a method for preparing nicardipine hydrochloride injection. The preparation method involves grinding nicardipine hydrochloride and solid polyhydroxy alcohol in a certain proportion to form a solid dispersion, and then dissolving it in water for injection at a temperature not exceeding 35°C. This method can greatly accelerate the dissolution rate of nicardipine hydrochloride in water, while also ensuring that the color of the resulting solution does not darken and reducing the generation of impurities. This avoids the need for a subsequent decolorization step using activated carbon, thus ensuring the safety and effectiveness of nicardipine hydrochloride injection. Attached Figure Description

[0035] Figure 1 This is an XRPD image obtained by grinding nicardipine hydrochloride and sorbitol at a ratio of 1:50.

[0036] Figure 2 This is an XRPD image obtained by grinding nicardipine hydrochloride and sorbitol at a ratio of 1:20.

[0037] Figure 3 The XRPD image is obtained by mixing nicardipine hydrochloride and sorbitol in a 1:20 ratio without grinding.

[0038] Figure 4 The image is a DSC diagram obtained by grinding nicardipine hydrochloride and sorbitol at a ratio of 1:20.

[0039] Figure 5 The image is a DSC diagram obtained by mixing nicardipine hydrochloride and sorbitol in a 1:20 ratio without grinding.

[0040] Figure 6 This is the related material spectrum of the sample in Example 1.

[0041] Figure 7 This is the related material spectrum of the sample in Comparative Example 7. Detailed Implementation

[0042] The present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. The following embodiments are only descriptive and not limiting, and should not be used to limit the scope of protection of the present invention. Unless otherwise specified, all raw materials used can be obtained commercially or in-house.

[0043] The impurity content and nicardipine hydrochloride content of the nicardipine hydrochloride injection solutions obtained in the embodiments and comparative examples of this invention were determined using high-performance liquid chromatography (HPLC). In both the embodiments and comparative examples of this invention, nitrogen purging was performed after filling to ensure that the headspace residual oxygen content of the injection solution after filling was not higher than 2%.

[0044] Example 1

[0045] This invention provides a method for preparing nicardipine hydrochloride injection, the steps of which are as follows:

[0046] Step 1: Grind 4.0g of nicardipine hydrochloride and 200.0g of sorbitol together to prepare a solid dispersion;

[0047] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0048] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to 4.0 kg to obtain drug solution 2;

[0049] Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0050] Example 2

[0051] This invention provides a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in that the grinding ratio of nicardipine hydrochloride to sorbitol is 1:20. The steps are as follows:

[0052] Step 1: Grind 4.0g of nicardipine hydrochloride and 80.0g of sorbitol together to prepare a solid dispersion;

[0053] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-35℃), stir to dissolve, and obtain drug solution 1;

[0054] Step 3: Add 120.0g of sorbitol to the solution 1 from Step 2, stir to dissolve, and obtain solution 2;

[0055] Step 4: Adjust the pH of the drug solution obtained in Step 3 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to 4.0 kg to obtain drug solution 3;

[0056] Step 5: Filter the drug solution 3 obtained in Step 4 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0057] Example 3

[0058] This invention provides a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in that the polyhydroxy alcohol is mannitol. The steps are as follows:

[0059] Step 1: Grind 4.0g of nicardipine hydrochloride and 200.0g of mannitol together to prepare a solid dispersion;

[0060] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0061] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to 4.0 kg to obtain drug solution 2;

[0062] Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0063] Example 4

[0064] This invention provides a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in that the polyhydroxy alcohol is inositol and the pH adjuster is acetic acid. The steps are as follows:

[0065] Step 1: Grind 4.0g of nicardipine hydrochloride and 200.0g of inositol together to prepare a solid dispersion;

[0066] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0067] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L acetic acid solution, and add water for injection to 4.0 kg to obtain drug solution 2;

[0068] Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0069] Example 5

[0070] This invention provides a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in that the polyhydroxy alcohol is xylitol and the pH adjuster is citric acid. The steps are as follows:

[0071] Step 1: Grind 4.0g of nicardipine hydrochloride and 200.0g of xylitol together to prepare a solid dispersion;

[0072] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0073] Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L citric acid solution, and add water for injection to 4.0 kg to obtain drug solution 2;

[0074] Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0075] Comparative Example 1

[0076] This invention provides a method for preparing nicardipine hydrochloride injection, which differs from Example 2 in that the grinding ratio of nicardipine hydrochloride to sorbitol is 1:10. The steps are as follows:

[0077] Step 1: Grind 4.0g of nicardipine hydrochloride and 40.0g of sorbitol together to prepare a solid dispersion;

[0078] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-35℃), stir to dissolve, and obtain drug solution 1;

[0079] Step 3: Add 180.0g of sorbitol to the drug solution 1 from Step 2, stir to dissolve, and obtain drug solution 2;

[0080] Step 4: Adjust the pH of the drug solution obtained in Step 3 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to 4.0 kg to obtain drug solution 3;

[0081] Step 5: Filter the drug solution 3 obtained in Step 4 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished Nicardipine Hydrochloride Injection Solution.

[0082] Comparative Example 2

[0083] This invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in that the grinding ratio of nicardipine hydrochloride to sorbitol is 1:60. The specific steps are as follows:

[0084] Step 1: Grind 4.0g of nicardipine hydrochloride and 240.0g of sorbitol together to prepare a solid dispersion;

[0085] Step 2: Add the solid dispersion obtained in Step 1 to 3.6 kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0086] Steps three and four are the same as steps three and four in Example 1.

[0087] Comparative Example 3

[0088] This invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in the order of addition. In this comparative example, nicardipine hydrochloride is first dissolved directly in water for injection, then sorbitol is added, and then the pH value is adjusted. The specific steps are as follows:

[0089] Step 1: Add 4.0g of nicardipine hydrochloride to 3.6kg of water for injection (18-26℃), stir and dissolve to obtain drug solution 1; Step 2: Add 200.0g of sorbitol to drug solution 1 obtained in Step 1, stir and dissolve to obtain drug solution 2;

[0090] Steps three and four are the same as steps three and four in Example 1.

[0091] Comparative Example 4

[0092] This invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in the order of addition. In this comparative example, sorbitol is dissolved first, then nicardipine hydrochloride is added and dissolved, followed by pH adjustment. The specific steps are as follows:

[0093] Step 1: Add 200.0g of sorbitol to 3.6kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0094] Step 2: Add 4.0g of nicardipine hydrochloride to the drug solution 1 obtained in Step 1, stir to dissolve, and obtain drug solution 2;

[0095] Steps three and four are the same as steps three and four in Example 1.

[0096] Comparative Example 5

[0097] This invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, which differs from Example 1 in the order of addition. In this comparative example, sorbitol is dissolved first, the pH value is adjusted, and then nicardipine hydrochloride is added to dissolve it. The specific steps are as follows:

[0098] Step 1: Add 200.0g of sorbitol to 3.6kg of water for injection (18-26℃), stir to dissolve, and obtain drug solution 1;

[0099] Step 2: Adjust the pH of the drug solution 1 obtained in Step 1 to 3.4 with 0.1 mol / L hydrochloric acid solution to obtain drug solution 2;

[0100] Step 3: Add 4.0g of nicardipine hydrochloride to the drug solution 2 obtained in Step 2, stir to dissolve, and obtain drug solution 3;

[0101] Step 4: Add water for injection to the solution 3 obtained in Step 3 to make a total of 4.0 kg, thus obtaining solution 4;

[0102] Step 5: Filter the drug solution 4 obtained in Step 4 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished nicardipine hydrochloride injection solution.

[0103] Comparative Example 6

[0104] The present invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, the preparation steps of which are similar to those of comparative example 3, except that the temperature of the solution is in the range of 36 to 45°C throughout the preparation process.

[0105] Comparative Example 7

[0106] The present invention provides a comparative example of a method for preparing nicardipine hydrochloride injection, the preparation steps of which are similar to those of comparative example 3, except that the temperature of the solution is in the range of 46 to 55°C throughout the preparation process.

[0107] Experimental Example 1

[0108] The solid dispersions obtained by grinding in step one of Examples 1 and 2 were analyzed by X-ray powder diffraction (XRPD). The test patterns are shown in the appendix. Figure 1 and attached Figure 2 The solid dispersion obtained by grinding in step one of Example 1 was analyzed by differential scanning calorimetry (DSC), and the test spectrum is shown in the appendix. Figure 3XRPD and DSC spectra of the unground nicardipine hydrochloride and sorbitol mixture sample were used as a control; the test spectra are attached. Figure 4 and attached Figure 5 .

[0109] Appendix Figure 1 Appendix Figure 2 abrasive and adhering Figure 3 Comparison of XRPD patterns of the mixtures revealed changes in the crystal diffraction characteristic peaks of both nicardipine hydrochloride and sorbitol after grinding at different ratios. In particular, the crystalline diffraction peaks of nicardipine hydrochloride completely disappeared, indicating that the crystal characteristics of nicardipine hydrochloride were suppressed and it existed in an amorphous state after forming a solid dispersion with sorbitol.

[0110] Literature reports that β-crystalline nicardipine hydrochloride injection exhibits a characteristic endothermic peak at 169℃ (the β-crystalline nicardipine hydrochloride used in this patent is β-crystalline). Figure 5 The endothermic peak of the drug is still visible in the DSC chromatogram of the physical mixture of nicardipine hydrochloride and sorbitol, but its position has shifted slightly forward to around 167℃, possibly due to interference from sorbitol. However, [the following text is incomplete and requires further context]. Figure 4 In the DSC diagram obtained by grinding nicardipine hydrochloride and sorbitol, the characteristic endothermic peaks of nicardipine hydrochloride completely disappeared, indicating a change in the phase state and the formation of a solid dispersion.

[0111] Experimental Example 2

[0112] The nicardipine hydrochloride injection solutions obtained in Examples 1-5 and Comparative Examples 1-7 were subjected to property identification, dissolution time determination, dissolution status assessment, osmotic pressure (mOsm / kg), and impurity content (%) and nicardipine hydrochloride content (%) in the injection solutions. The test results are shown in Tables 1 and 2.

[0113] Table 1. Test results for items corresponding to Examples 1-5.

[0114]

[0115]

[0116] Table 2 shows the test results for items corresponding to Comparative Examples 1-7.

[0117]

[0118] The data above show that the nicardipine hydrochloride injection prepared in Comparative Example 1 (nicardipine hydrochloride: sorbitol = 1:10) had a significantly longer dissolution time compared to Examples 1-5. Although the dissolution, total impurities, and content of the nicardipine hydrochloride injection prepared in Comparative Example 2 (nicardipine hydrochloride: sorbitol = 1:60) were not significantly different from Examples 1-5, its osmotic pressure was significantly higher than that of the examples due to the presence of 6% w / v sorbitol, exceeding the isotonic range for humans (260-320 mOsm / kg), thus affecting product safety. These two comparative examples demonstrate that a mass ratio of nicardipine hydrochloride to sorbitol of 1:10 and 1:60 is unsuitable; the optimal mass ratio range is 1:20 to 1:50.

[0119] Further analysis of the data from Examples 1-5 and Comparative Examples 3-7 revealed that, compared to the nicardipine hydrochloride injections prepared in Comparative Examples 3-5, the dissolution time of the nicardipine hydrochloride injections prepared in Examples 1-5 was significantly shortened, and there was no wall adhesion during dissolution, indicating a greatly improved dissolution process. Compared to the nicardipine hydrochloride injections prepared in Comparative Examples 6 and 7, the finished products prepared in Examples 1-5 had a lighter color and a significantly reduced total amount of impurities. (See Appendix...) Figure 7 It can be seen that as the temperature of water for injection increases, the total amount of impurities increases significantly. Therefore, the optimal temperature range for water for injection is 18–35℃.

Claims

1. A method for preparing nicardipine hydrochloride injection, characterized in that, Includes the following steps: Step 1: Nicardipine hydrochloride and solid polyhydroxy alcohol are ground in a specific ratio to prepare a solid dispersion; the mass ratio of nicardipine hydrochloride to polyhydroxy alcohol is 1:20 to 1:

50. The polyhydroxy alcohols include one or more of sorbitol, mannitol, xylitol, and inositol; Step 2: Add the solid dispersion obtained in Step 1 to 80% to 90% of the prescribed amount of water for injection, stir to dissolve, and obtain drug solution 1. The temperature of the water for injection is 18 to 35°C. Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.0-5.0 with acid solution, and add the remaining amount of water for injection to obtain drug solution 2; The acid solution includes one or more of hydrochloric acid, acetic acid, and citric acid; Step 4: Filter the drug solution 2 obtained in Step 3, fill it with nitrogen, seal it, and sterilize it to obtain the finished product of nicardipine hydrochloride injection; the concentration of nicardipine hydrochloride is 0.1% to 0.6% W / V, and the concentration of polyhydroxy alcohol is 2% to 5% W / V; the filtration is carried out using a single or multiple filter membranes with a pore size of 0.22 μm.

2. The method for preparing nicardipine hydrochloride injection according to claim 1, characterized in that, The grinding described in step one is not limited to the grinding method, and the grinding time is not limited. The DSC and X-ray powder diffraction patterns of the sample after grinding are used as the endpoint for judgment.

3. The method for preparing nicardipine hydrochloride injection according to claim 1, characterized in that, The temperature of the water for injection in step two is 18–26°C.

4. The method for preparing nicardipine hydrochloride injection according to claim 1, characterized in that, The pH of the acid solution mentioned in step three is adjusted to 3.1 to 3.

5.

5. The method for preparing nicardipine hydrochloride injection according to claim 1, characterized in that, In the nicardipine hydrochloride injection described in step four, the concentration of nicardipine hydrochloride is 0.1% W / V; the concentration of the polyhydroxy alcohol is 5% W / V.

6. The method for preparing nicardipine hydrochloride injection according to claim 1, characterized in that, The nitrogen purging mentioned in step four is to ensure that the headspace residual oxygen content of the injection solution after filling is not higher than 2%, so as to reduce impurities generated during storage. The sterilization temperature is 121℃ and the sterilization time is 12-15 minutes to ensure the sterility of the product.

7. A method for preparing nicardipine hydrochloride injection, characterized in that, Includes the following steps: Step 1: Grind 0.1% w / v nicardipine hydrochloride and 5% w / v sorbitol together to prepare a solid dispersion; Step 2: Add the solid dispersion obtained in Step 1 to 80%-90% of the prescribed amount of water for injection, wherein the temperature of the water for injection is 18-26℃, stir to dissolve, and obtain drug solution 1; Step 3: Adjust the pH of the drug solution obtained in Step 2 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to the prescribed volume to obtain drug solution 2; Step 4: Filter the drug solution 2 obtained in Step 3 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished nicardipine hydrochloride injection solution.

8. A method for preparing nicardipine hydrochloride injection, characterized in that, Includes the following steps: Step 1: Grind 0.1% w / v nicardipine hydrochloride and 2% w / v sorbitol together to prepare a solid dispersion; Step 2: Add the solid dispersion obtained in Step 1 to 80%-90% of the prescribed amount of water for injection, wherein the temperature of the water for injection is 18-26℃, stir to dissolve, and obtain drug solution 1; Step 3: Add 3% w / v sorbitol to solution 1 from step 2, stir to dissolve, and obtain solution 2; Step 4: Adjust the pH of the drug solution obtained in Step 3 to 3.1-3.5 with 0.1 mol / L hydrochloric acid solution, and add water for injection to the prescribed volume to obtain drug solution 3; Step 5: Filter the drug solution 3 obtained in Step 4 through two 0.22μm PVDF filter membranes, fill it into 12ml brown borosilicate glass ampoules, fill with nitrogen, seal, and sterilize at 121℃ for 15min to obtain the finished nicardipine hydrochloride injection solution.

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