A morpholinylguanidine hydrochloride tablet and a method for preparing the same

Abstract

The present invention provides a morpholinoguanidine hydrochloride tablet and a preparation method thereof, comprising a tablet core and a coating, wherein the tablet core is made of the following raw materials in percentage by weight: morpholinoguanidine hydrochloride 32%-45%, microcrystalline cellulose 20%-25%, lactose 25%-30%, croscarmellose sodium 3%-8%, povidone K 25 3%-5%, magnesium stearate 1.2%-2%; the particle size of the morpholinoguanidine hydrochloride is D 90 15-20 μm, D 50 The microcrystalline cellulose is preferably microcrystalline cellulose KG802; the morpholino hydrochloride prepared by the present invention has high and stable solubility and can be stored for 6 months with stable quality.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations and relates to a morphine hydrochloride tablet and a preparation method thereof. Background Art

[0002] Moroxydine Hydrochloride, also known as morpholinimidazole, morpholinobiguanide, morpholinobiguanide, and ABOB, has a chemical name of NN-(2-guanidino-ethylimino)-morpholine hydrochloride and a structural formula shown below. It is an antiviral drug. It is readily soluble in water and has a slightly bitter taste. It inhibits viral DNA and RNA polymerases, thereby inhibiting viral reproduction. In vitro, a 1% concentration has significant inhibitory effects against DNA viruses (adenoviruses, herpes viruses) and RNA viruses (echoviruses), and exhibits inhibitory effects at all stages of the viral proliferation cycle.

[0003]

[0004] Domestic preparations of guanidine hydrochloride primarily include guanidine hydrochloride tablets, guanidine hydrochloride injection, and guanidine hydrochloride eye drops. Of these, guanidine hydrochloride tablets have the most manufacturers, exceeding 200. The Beijing Military Region Joint Logistics Department's Drug and Instrument Testing Institute conducted sampling tests on this drug, and the results showed that dissolution rates met requirements. However, significant differences can be observed in the quality of guanidine hydrochloride tablets produced by different manufacturers, and even within the same manufacturer and within the same batch, primarily in dissolution behavior.

[0005] Morphoguanidine hydrochloride tablets are oral tablets that are simple and convenient to take, but they taste bitter. For patients with swallowing disorders caused by viral infections, the drug may cause throat blockage and may dissolve. The bitter taste of the drug will affect the patient's medication experience.

[0006] Therefore, it is necessary to further study the prescription and preparation method of morpholino hydrochloride tablets to improve the dissolution behavior of morpholino hydrochloride tablets and the patient's medication experience. Summary of the Invention

[0007] The inventors of the present invention unexpectedly discovered during their research that by strictly controlling the particle size of morpholino hydrochloride and the model, composition, and particle size of the excipients, and optimizing the preparation method, the morpholino hydrochloride tablets prepared have high and stable solubility and maintain stable quality after accelerated storage for 6 months.

[0008] First, the present invention provides a morpholinoguanidine hydrochloride tablet, comprising a tablet core and a coating, wherein the tablet core is made of the following raw materials in percentage by weight: morpholinoguanidine hydrochloride 32%-45%, microcrystalline cellulose 20%-25%, lactose 25%-30%, croscarmellose sodium 3%-8%, povidone K 25 3%-5%, magnesium stearate 1.2%-2%; the particle size of the morpholinoguanidine hydrochloride is D90 is 15-20 μm, D 50 is 8-12 μm; the microcrystalline cellulose is preferably microcrystalline cellulose KG802.

[0009] In some embodiments of the present application, the tablet core is made from the following raw materials in the following weight percentages: moroxydine hydrochloride 35%-40%, microcrystalline cellulose 21%-24%, lactose 25%-30%, croscarmellose sodium 3%-8%, povidone K 25 3%-5%, magnesium stearate 1.2%-2%.

[0010] In some embodiments of the present application, the tablet core is made from the following raw materials in the following weight percentages: moroxydine hydrochloride 36%-39%, microcrystalline cellulose 20%-25%, lactose 25%-30%, croscarmellose sodium 3%-8%, povidone K 25 3%-5%, magnesium stearate 1.2%-2%.

[0011] In some embodiments of the present application, the tablet core is made from the following raw materials in the following weight percentages: moroxydine hydrochloride 36%-39%, microcrystalline cellulose 21%-24%, lactose 25%-30%, croscarmellose sodium 3%-8%, povidone K 25 3%-5%, magnesium stearate 1.2%-2%.

[0012] The microcrystalline cellulose is preferably microcrystalline cellulose KG802.

[0013] The particle size D 90 of the moroxydine hydrochloride is 15-20 μm, D 50 of the moroxydine hydrochloride is 8-12 μm.

[0014] Further, the coating is made from the following raw materials in the following weight percentages: ethyl cellulose 35%-50%, maltose 35%-50%, talc 1.2%-2.0%, titanium dioxide 2%-3%, povidone K 25 5%-10%.

[0015] In some embodiments of the present application, the coating is made from the following raw materials in the following weight percentages: ethyl cellulose 32%-37%, maltose 32%-37%, talc 1.2%-2.0%, titanium dioxide 2%-3%, povidone K 25 5%-10%

[0016] Further, the weight ratio of the coating to the tablet core is 8-12:1; preferably 10:1.

[0017] Further, the moroxydine hydrochloride tablet contains 0.1 g-0.5 g, preferably 0.1 g of moroxydine hydrochloride.

[0018] Another object of the present application is to provide a method for preparing the above-mentioned morpholinoguanidine tablet.

[0019] (1) Pre-treatment of excipients;

[0020] ① Microcrystalline cellulose and lactose are mixed and pulverized to obtain a microcrystalline cellulose-lactose mixture with an average particle size of 30-40 μm, which is ready for use.

[0021] ② Polyvinylpyrrolidone K25 is dissolved in water to prepare a solution with a concentration of 5wt%-10wt% as a binder solution, which is ready for use.

[0022] ③ Ethyl cellulose, maltose, talc, titanium dioxide, polyvinylpyrrolidone K 25 Add 20-25 times the weight of the coating to ethanol, stir, and homogenize to obtain a coating solution, which is ready for use.

[0023] (2) Pre-mixing and wet granulation:

[0024] Add morpholinoguanidine hydrochloride, microcrystalline cellulose-lactose mixture, and cross-linked sodium carboxymethyl cellulose to a wet mixing granulator for stirring and pre-mixing, then add the binder solution under stirring conditions for wet granulation; control the spraying speed of the binder solution, uniformly spray the binder solution, and the spraying process lasts for 140-180 seconds, and the granulation time after spraying is 120-180 seconds.

[0025] (3) Drying and granulating:

[0026] Drying at 50-55℃, the weight loss is not more than 1.2%; the dried granules are added to a granulator with a screen mesh size of 2.0 mm.

[0027] (4) Tabletting: Add magnesium stearate to the granules and press them into tablets to obtain the tablet core.

[0028] (5) Coating: Coating is performed by a spray coating machine, and the coating is stopped when the weight gain is 5wt%-7wt%, and then the product is dried at room temperature to obtain the morpholinoguanidine hydrochloride tablet.

[0029] In step (3), preferably 52-54℃, more preferably reduced pressure vacuum drying.

[0030] In step (2), the particle size D 90 of morpholinoguanidine hydrochloride is 15-20 μm, and D 50 is 8-12 μm.

[0031] Further, in step (3), the granules have a particle size distribution of:

[0032]

[0033] Further, in step (5), each tablet contains 0.1 g of morpholinylguanidine hydrochloride, and each tablet weighs 0.25-0.30 g.

[0034] The present application controls the particle size of morpholinylguanidine hydrochloride and the type, composition and particle size of the excipients strictly, optimizes the preparation method, and the prepared morpholinylguanidine hydrochloride tablets have high dissolution rate and stability, and the quality is stable after accelerated storage for 6 months. DETAILED DESCRIPTION

[0035] The present application discloses a preparation method of morpholinylguanidine hydrochloride tablets. Those skilled in the art can refer to the content of the present application, combine the relevant principles of pharmaceutical preparations, and appropriately improve the process parameters to realize. It should be particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are considered to be included in the scope of the present application. The application of the present application has been described by the preferred embodiments, and the relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present application to realize and apply the present application technology.

[0036] In order to better understand the present application without limiting the scope of the present application, all numbers, percentages and other numerical values used in this application are understood to be modified by the word "about" in all cases. Each numerical parameter should be considered to be at least as accurate as the rounding method applied to the reported significant digits and to the application of the conventional rounding methods.

[0037] The present application is further illustrated by the following examples, but the examples do not limit the present application in any way.

[0038] The particle size of morpholinylguanidine hydrochloride used in the embodiments of the present application is shown in the following table:

[0039]

[0040] Determination of dissolution curve

[0041] Dissolution medium: water; 1000 ml; rotation speed: 50 rpm

[0042] Sampling time: 3 min, 6 min, 10 min, 15 min, 20 min, 30 min

[0043] Examples 1-3: morpholinylguanidine hydrochloride tablets

[0044] I. Prescription composition:

[0045]

[0046] According to the prescription amount of 10000 tablets, morpholinylguanidine hydrochloride tablets were prepared. The same applies.

[0047] II. Preparation method:

[0048] (1) Pre-treatment of excipients;

[0049] ① Microcrystalline cellulose and lactose were mixed and crushed, with average particle sizes of 32.1 μm, 33.6 μm and 35.7 μm, respectively, to obtain a microcrystalline cellulose-lactose mixture, which was used as needed.

[0050] ② Povidone K25 was dissolved in water to prepare a solution with a concentration of 7 wt%, which was used as a binder solution.

[0051] ③ Ethyl cellulose, maltose, talc, titanium dioxide, povidone K 25 Ethanol was added at 22 times the weight of the coating, and stirring and homogenization were performed to obtain a coating solution, which was used as needed.

[0052] (2) Pre-mixing and wet granulation:

[0053] Hydrochloride guanazole, microcrystalline cellulose-lactose mixture and sodium croscarmellose were added to a wet mixing granulator and stirred for pre-mixing. Then, the binder solution was sprayed under stirring conditions for wet granulation. The spraying speed of the binder solution was controlled, and the binder solution was uniformly sprayed. The spraying process of the binder solution lasted for 160 seconds, and the granulation time after spraying was 150 seconds.

[0054] (3) Drying and granulation:

[0055] Drying was performed at 52-54°C, and the weight loss was not higher than 1.2%. The dried granules were added to a granulator with a screen mesh size of 2.0 mm.

[0056]

[0057] (4) Tabletting: magnesium stearate was added to the granules, and tabletting was performed to obtain a tablet core.

[0058] (5) Coating: coating was performed by a spray coating machine. When the coating weight increased to 6 wt%, the coating was stopped. The tablets were dried at room temperature for 48 hours to obtain hydrochloride guanazole tablets.

[0059] III. Test results:

[0060] The dissolution curve of the prepared hydrochloride guanazole tablets in water was determined, and the results are shown in the following table.

[0061]

[0062] Example 4-6: Hydrochloride guanazole tablets

[0063] I. Prescription composition:

[0064]

[0065] II. Preparation method:

[0066] (1) Pre-treatment of excipients;

[0067] ① Microcrystalline cellulose and lactose were mixed and pulverized, with average particle sizes of 31.1 μm, 36.4 μm and 38.8 μm, respectively, to obtain a microcrystalline cellulose-lactose mixture, which was used as needed.

[0068] ② Polyvinylpyrrolidone K25 was dissolved in water to prepare a solution with a concentration of 8 wt%, which was used as a binder solution.

[0069] ③ Ethyl cellulose, maltose, talc, titanium dioxide, polyvinylpyrrolidone K 25 Ethanol was added at 22 times the weight of the coating, and stirring and homogenization were performed to obtain a coating solution, which was used as needed.

[0070] (2) Pre-mixing and wet granulation:

[0071] The wet granulation machine was added with morpholinylguanidine hydrochloride 2, microcrystalline cellulose-lactose mixture and croscarmellose sodium, and stirring and pre-mixing were performed. Then, the binder solution was sprayed under stirring conditions to perform wet granulation. The spraying speed of the binder solution was controlled, and the binder solution was uniformly sprayed. The duration of the binder solution spraying process was 170 seconds, and the granulation time after spraying was 160 seconds.

[0072] (3) Drying and granulation:

[0073] Drying was performed at 52-54°C, and the weight loss was not higher than 1.2%. The dried granules were added to the granulator, and the screen mesh size of the granulator was 2.0 mm.

[0074]

[0075] (4) Tabletting: magnesium stearate was added to the granules, and tabletting was performed to obtain a tablet core.

[0076] (5) Coating: coating was performed by a spray coating machine. When the coating weight increased by 5 wt%, the coating was stopped. The sample was dried and solidified at room temperature for 48 hours to obtain morpholinylguanidine hydrochloride tablets.

[0077] III. Test results:

[0078] The dissolution curve of the prepared morpholinylguanidine hydrochloride tablets in water was determined, and the results are shown in the following table.

[0079]

[0080] The prepared morpholinylguanidine hydrochloride tablets of Examples 1-6 not only have similar dissolution among different examples, with dissolution not less than 85% within 30 min, but also have stable dissolution among the same batch (RSD of dissolution results at the first time point 3 min is less than 10%; RSD of dissolution results from 6 min to 30 min is less than 5%).

[0081] Comparative Examples 1-3: Influence of particle size of morpholinylguanidine hydrochloride

[0082] I. Prescription composition: The used morpholinylguanidine hydrochloride is shown in the following table, and the rest is the same as Example 1.

[0083]

[0084] II. Preparation method: the same as Example 1.

[0085] III. Test results:

[0086] The prepared morpholinylguanidine hydrochloride tablets were subjected to dissolution curve determination in water, and the results are shown in the following table.

[0087]

[0088] Comparative analysis of Example 1 and Comparative Examples 1-3 shows that the particle size of morpholinylguanidine hydrochloride influences the dissolution of morpholinylguanidine hydrochloride tablets. Only morpholinylguanidine hydrochloride with a specific particle size range (D 90 15-20 μm, D 50 8-12 μm) can produce morpholinylguanidine hydrochloride tablets with high dissolution (dissolution not less than 85% within 30 min) and stable dissolution (RSD of dissolution results at the first time point 3 min is less than 10%; RSD of dissolution results from 6 min to 30 min is less than 5%). When other particle sizes of morpholinylguanidine hydrochloride are used, the prepared morpholinylguanidine hydrochloride tablets have slow dissolution (such as Comparative Example 3) and unstable dissolution (RSD of dissolution results at the first time point 3 min and the second time 6 min is higher than 10%; RSD of dissolution results at the third time 10 min and the fourth time point 15 min is higher than 5%).

[0089] Comparative Examples 4-5: Influence of type of microcrystalline cellulose

[0090] I. Prescription composition: The used type of microcrystalline cellulose is shown in the following table, and the rest is the same as Example 1.

[0091]

[0092] II. Preparation method: the same as Example 1.

[0093] III. Test results:

[0094] The dissolution curve of the prepared morpholinylguanidine hydrochloride tablets in water was determined, and the results are shown in the following table.

[0095]

[0096] Comparative analysis of Example 1 and Comparative Examples 4-5 found that the type of excipient microcrystalline cellulose did not affect the dissolution behavior of the morpholinylguanidine hydrochloride tablets at the beginning of preparation (0 days), whether it was microcrystalline cellulose KG802 of Example 1, or KG802 or KG1000 of Comparative Examples 4-5, the prepared morpholinylguanidine hydrochloride tablets had high dissolution (dissolution was not less than 85% within 30 min) and stable dissolution (RSD of dissolution results at the first time point 3 min was less than 10%; RSD of dissolution results from 6 min to 30 min was less than 5%), but when accelerated for 6 months, as shown in the data of Example 7, the morpholinylguanidine hydrochloride tablets of Comparative Examples 4-5 had the problem of unstable dissolution (RSD of dissolution results at the first time point 3 min was more than 10%; RSD of dissolution results at the second time point 6 min and the third time point 10 min was more than 5%), and the product quality difference was large. Therefore, KG802 is preferred.

[0097] Comparative Examples 6-7: Effect of Povidone Type

[0098] I. Prescription composition: The type of povidone used is shown in the following table, and the rest is the same as Example 1.

[0099]

[0100] II. Preparation method: same as Example 1.

[0101] III. Test results

[0102] The dissolution curve of the prepared morpholinylguanidine hydrochloride tablets in water was determined, and the results are shown in the following table.

[0103]

[0104] Comparative analysis of Example 1 and Comparative Example 7 found that the use of povidone K90 to prepare morpholinylguanidine hydrochloride tablets had the problem of unstable dissolution (RSD of dissolution results at the first time point 3 min was more than 10%; RSD of dissolution results at the second time point 6 min and the third time point 10 min was more than 5%) at the beginning of preparation (0 days), and the quality difference of the products prepared in the same batch was large.

[0105] A comparative analysis of Example 1 and Comparative Example 6 revealed that, at the beginning of preparation (day 0), the use of povidone K30 did not affect the dissolution behavior of the morpholinoguanidine hydrochloride tablets. The prepared morpholinoguanidine hydrochloride tablets had a high solubility (no less than 85% dissolution within 30 minutes) and stable dissolution (RSD of the dissolution results at the first time point of 3 minutes was less than 10%; RSD of the dissolution results from 6 minutes to 30 minutes was less than 5%). However, after accelerated storage for 6 months, as shown in the data of Example 7, the morpholinoguanidine hydrochloride tablets of Comparative Example 6 showed unstable dissolution (RSD of the dissolution results at the first time point of 3 minutes was greater than 10%; RSD of the dissolution results at the second time point of 6 minutes and the third time point of 10 minutes was greater than 5%). The quality of products prepared in the same batch varied greatly. Therefore, povidone K25 is preferred.

[0106] Comparative Examples 8-9: Effect of Microcrystalline Cellulose Lactose Mixture

[0107] 1. Prescription composition: Same as Example 1.

[0108] 2. Preparation method: Step (1)-① is as shown in the following table, and the remaining steps are the same as in Example 1

[0109]

[0110] 3. Test results:

[0111] The dissolution curve of the prepared morpholinoguanidine hydrochloride tablets was measured in water, and the results are shown in the following table.

[0112]

[0113] Comparative analysis of Example 1 and Comparative Examples 8-9 revealed that at the beginning of preparation (day 0), the mixing method and particle size of microcrystalline cellulose lactose did not affect the dissolution behavior of morpholino hydrochloride tablets. Regardless of whether the mixture was crushed after mixing in Example 1, crushed after mixing in Comparative Example 8, or the different particle sizes in Comparative Example 9, the prepared morpholino hydrochloride tablets had high solubility (not less than 85% dissolved within 30 minutes) and stable dissolution (RSD of the dissolution result at the first time point of 3 minutes was less than 10%; RSD of the dissolution result from 6 minutes to 30 minutes was less than 5%). However, after accelerated storage for 6 months, as shown in the data of Example 7, the morpholino hydrochloride tablets of Comparative Examples 8-9 showed unstable dissolution (RSD of the dissolution result at the first time point of 3 minutes was greater than 10%; RSD of the dissolution result at the second time point of 6 minutes and the third time point of 10 minutes was greater than 5%), resulting in significant differences in product quality. Therefore, it is preferred to crush the mixture after mixing and control the average particle size of the mixture to 30-40 μm.

[0114] Comparative Examples 10-11: Effect of Coating

[0115] I. Prescription composition: tablet core is the same as example 1, and the coating composition is as follows:

[0116]

[0117] II. Preparation method: the same as example 1

[0118] III. Test results:

[0119] The dissolution curve of the prepared morpholinylguanidine hydrochloride tablets in water was determined, and the results are shown in the following table.

[0120]

[0121] Comparative analysis of example 1 and comparative example 10 found that the composition of the coating solution affects the dissolution behavior. When the weight ratio of ethyl cellulose to maltose in the coating solution is 2:1, the prepared morpholinylguanidine hydrochloride tablet core has the problem of unstable dissolution (RSD of dissolution results at the first time point 3 min and the second time point 6 min is higher than 10%; RSD of dissolution results at the third time point 10 min and the fourth time point 15 min is higher than 5%) at the beginning of preparation (0 days), and the quality difference of the products prepared in the same batch is large.

[0122] Comparative analysis of example 1 and comparative example 11 found that when the weight ratio of ethyl cellulose to maltose in the coating solution is 1:2 at the beginning of preparation (0 days), it does not affect the dissolution behavior of morpholinylguanidine hydrochloride tablets. The prepared morpholinylguanidine hydrochloride tablets have high dissolution (dissolution is not less than 85% within 30 min) and stable dissolution (RSD of dissolution results at the first time point 3 min is less than 10%; RSD of dissolution results from 6 min to 30 min is less than 5%), but test example 1 shows that the morpholinylguanidine hydrochloride tablets prepared in comparative example 11 release morpholinylguanidine hydrochloride in simulated oral fluid, which will release the bitter taste of the drug in actual medication, and the medication experience is poor.

[0123] Therefore, the ratio of ethyl cellulose to maltose in the coating is preferably 1:1.

[0124] Test example 1:

[0125] The morpholinylguanidine hydrochloride tablets prepared by the preparation methods of examples 1-6, comparative examples 4-6, comparative examples 8-9, and comparative example 11 were taken as samples, 3 tablets were randomly taken from each group, 10 mL of artificial saliva was added to each small cup, and one morpholinylguanidine hydrochloride tablet was added. At 30s and 60s, part of the solution was taken out for content detection, and the dissolution amount (%) of morpholinylguanidine hydrochloride at 30s and 60s was calculated. The test data is averaged and summarized in the following table.

[0126]

[0127] The salt of hydrochloric acid morpholinyl guanidine tablets prepared in Examples 1-6, Comparative Examples 4-6, Comparative Examples 8-9 are released in the simulated oral fluid, and no drug bitter taste is released within 60s in actual medication, improving the medication experience; the salt of hydrochloric acid morpholinyl guanidine prepared in Comparative Example 11 is released in the simulated oral fluid, and the drug bitter taste is released within 60s in actual medication, and the medication experience is poor.

[0128] Example 7: Stability test

[0129] The salt of hydrochloric acid morpholinyl guanidine tablets prepared in Examples 1-6, Comparative Examples 4-6, Comparative Examples 8-9 are placed at a temperature of 40℃±2℃; relative humidity of 75%±5% (accelerated) for 6 months, and sampled at the end of the 6th month, and the dissolution curve is determined in water, and the results are shown in the following table.

[0130] Dissolution curve of the salt of hydrochloric acid morpholinyl guanidine tablets prepared in Examples 1-6 in water after accelerated storage for 6 months

[0131]

[0132] Dissolution curve of the salt of hydrochloric acid morpholinyl guanidine tablets prepared in Comparative Examples 4-6, Comparative Examples 8-9 in water after accelerated storage for 6 months

[0133]

[0134] The salt of hydrochloric acid morpholinyl guanidine tablets prepared in Examples 1-6 is placed under accelerated conditions for 6 months, and the dissolution behavior does not change significantly, and it can be seen that the salt of hydrochloric acid morpholinyl guanidine tablets prepared in the present application is stable in dissolution.

[0135] The salt of hydrochloric acid morpholinyl guanidine tablets prepared in Comparative Examples 4-6, Comparative Examples 8-9 is unstable in dissolution after accelerated storage for 6 months.

Claims

1. A morpholinoguanidine hydrochloride tablet comprising a core and a coating, wherein the core is made of the following raw materials in percentage by weight: 32%-45% morpholinoguanidine hydrochloride, 20%-25% microcrystalline cellulose, 25%-30% lactose, 3%-8% croscarmellose sodium, and povidone K. 25 3%-5%, magnesium stearate 1.2%-2%; The particle size D of the morpholinoguanidine hydrochloride 90 15-20μm, D 50 8-12μm; The microcrystalline cellulose is microcrystalline cellulose KG802; The coating is made of the following raw materials in percentage by weight: 35%-50% ethyl cellulose, 35%-50% maltose, 1.2%-2.0% talc, 2%-3% titanium dioxide, and povidone K. 25 5%-10%; The preparation method of the morpholinguanidine hydrochloride tablets comprises the following steps: (1) Pretreatment of auxiliary materials; ① Mix microcrystalline cellulose and lactose, grind them into a mixture with an average particle size of 30-40 μm to obtain a microcrystalline cellulose lactose mixture, and set aside; ② Dissolve povidone K25 in water to prepare a solution with a concentration of 5wt%-10wt% as an adhesive solution for later use; ③ Ethyl cellulose, maltose, talcum powder, titanium dioxide, povidone K 25 Add 20-25 times the weight of the coating ethanol, stir, and homogenize to obtain a coating solution for later use; (2) Premixing and wet granulation: Adding guanidine hydrochloride, a microcrystalline cellulose lactose mixture, and croscarmellose sodium to a wet mixing granulator for stirring and premixing, and then adding a binder solution under stirring, and wet granulating; controlling the injection speed of the binder solution and spraying the binder solution uniformly, so that the injection process lasts for 140-180 seconds, and the granulation time after the injection is completed is 120-180 seconds; (3) Drying and granulation: Dry at 50-55℃, and the drying loss is not higher than 1.2%; the dried granules are added to a granulator with a sieve aperture of 2.0mm; (4) Tableting: Add magnesium stearate to the granules and compress the granules to obtain tablet cores; (5) Coating: Coating is performed using a spray coating machine. When the coating weight gain reaches 5 wt% to 7 wt%, coating is completed. The tablets are cured and dried at room temperature to obtain morpholinoguanidine hydrochloride tablets.

2. The morphine guanidine hydrochloride tablets according to claim 1, wherein The tablet core is made of the following raw materials in percentage by weight: 35%-40% morpholinoguanidine hydrochloride, 21%-24% microcrystalline cellulose, 25%-30% lactose, 3%-8% cross-linked carboxymethyl cellulose sodium, and povidone K. 25 3%-5%, magnesium stearate 1.2%-2%.

3. The morphine guanidine hydrochloride tablets according to claim 1, wherein The tablet core is made of the following raw materials in percentage by weight: 36%-39% of morpholinoguanidine hydrochloride, 20%-25% of microcrystalline cellulose, 25%-30% of lactose, 3%-8% of cross-linked carboxymethyl cellulose sodium, and 1%-2% of povidone K. 25 3%-5%, magnesium stearate 1.2%-2%.

4. The morphine guanidine hydrochloride tablets according to claim 1, wherein The tablet core is made of the following raw materials in percentage by weight: 36%-39% of morpholinoguanidine hydrochloride, 21%-24% of microcrystalline cellulose, 25%-30% of lactose, 3%-8% of cross-linked carboxymethyl cellulose sodium, and 1%-2% of povidone K. 25 3%-5%, magnesium stearate 1.2%-2%.

5. The morphine guanidine hydrochloride tablets according to claim 1, wherein The coating is made of the following raw materials in percentage by weight: 32%-37% ethyl cellulose, 32%-37% maltose, 1.2%-2.0% talc, 2%-3% titanium dioxide, and povidone K. 25 5%-10%.

6. A method for preparing the morphine guanidine hydrochloride tablets according to any one of claims 1 to 5, characterized in that: The steps include: (1) Pretreatment of auxiliary materials; ① Mix microcrystalline cellulose and lactose, grind them into a mixture with an average particle size of 30-40 μm to obtain a microcrystalline cellulose lactose mixture, and set aside; ② Dissolve povidone K25 in water to prepare a solution with a concentration of 5wt%-10wt% as an adhesive solution for later use; ③ Ethyl cellulose, maltose, talcum powder, titanium dioxide, povidone K 25 Add 20-25 times the weight of the coating ethanol, stir, and homogenize to obtain a coating solution for later use; (2) Premixing and wet granulation: Adding guanidine hydrochloride, a microcrystalline cellulose lactose mixture, and croscarmellose sodium to a wet mixing granulator for stirring and premixing, and then adding a binder solution under stirring, and wet granulating; controlling the injection speed of the binder solution and spraying the binder solution uniformly, so that the injection process lasts for 140-180 seconds, and the granulation time after the injection is completed is 120-180 seconds; (3) Drying and granulation: Dry at 50-55℃, and the drying loss is not higher than 1.2%; the dried granules are added to a granulator with a sieve aperture of 2.0mm; (4) Tableting: Add magnesium stearate to the granules and compress the granules to obtain tablet cores; (5) Coating: Coating is performed using a spray coating machine. When the coating weight gain reaches 5 wt% to 7 wt%, coating is completed. The tablets are cured and dried at room temperature to obtain morpholinoguanidine hydrochloride tablets.

7. The preparation method according to claim 6, wherein In step (3), the product is dried under reduced pressure at 52-54°C.

8. The preparation method according to claim 6, wherein In the step (3), the granules are sized, and the particle size distribution of the granules after granulation is: 。

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