Eperisone hydrochloride-containing pharmaceutical composition capable of effectively controlling content of impurity D and preparation method thereof

Abstract

The invention discloses an eperisone hydrochloride-containing pharmaceutical composition capable of effectively controlling the content of an impurity D and a preparation method of the eperisone hydrochloride-containing pharmaceutical composition. The eperisone hydrochloride-containing pharmaceutical composition comprises eperisone hydrochloride, hydrochloric acid, a filler, an adhesive, a disintegrating agent and a lubricant, and the hydrochloric acid can inhibit the eperisone hydrochloride in the eperisone hydrochloride-containing pharmaceutical composition from being degraded into the impurity D. The preparation process is simple, hydrochloric acid is adopted as a pH regulator, eperisone hydrochloride in the pharmaceutical composition can be effectively inhibited from being degraded into the impurity D, the content of the impurity D in the prepared pharmaceutical composition can be zero, and the impurity D is still not detected under the high-temperature condition; according to the pharmaceutical composition containing eperisone hydrochloride, the stability of the pharmaceutical composition containing eperisone hydrochloride can be greatly improved, the impurity level of the pharmaceutical composition is better controlled, the product quality is better, the safety to patients is higher, and the medication safety and effectiveness of the pharmaceutical composition are greatly improved.

Description

Technical Field

[0001] The invention relates to the technical field of impurity control in eperisone hydrochloride tablets, and in particular to a pharmaceutical composition containing eperisone hydrochloride capable of effectively controlling the content of impurity D and a preparation method thereof. Background Art

[0002] Eperisone hydrochloride is a centrally acting skeletal muscle relaxant that works by relaxing skeletal and vascular smooth muscle and exhibits a variety of effects, such as reducing myotonia, improving systemic circulation, and inhibiting pain reflexes. The drug inhibits the vicious cycle of myotonia by alleviating pain, ischemia, and hypertonia of skeletal muscles, thereby relieving stiffness and spasms and promoting muscle movement. The drug can also improve dizziness and tinnitus associated with cerebrovascular disease or cervical spondylosis. Compared with other antispasmodics, eperisone has a weaker central sedative effect while also promoting voluntary movements of the upper and lower limbs without reducing muscle strength. Therefore, the drug is often used in the initial stages of rehabilitation and as an adjuvant in subsequent physical therapy.

[0003] Eperisone hydrochloride mainly produces the following organic impurities during the synthesis and degradation process:

[0004]

[0005] The impurity control of eperisone hydrochloride is carried out in accordance with the relevant regulations of ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use). ICH requires that the content of a single impurity shall not exceed 0.1%. Regarding the impurities of epidermis hydrochloride, patent application number CN202311270724.3 discloses a stable epidermis hydrochloride tablet and a preparation method thereof, comprising the following components in weight percentage, 55-65% epidermis hydrochloride, 25-40% filler, 1-10% disintegrant, 0.1-3% binder, 1-5% silicon dioxide, 0.1-3% lubricant, 0.5-5% citric acid, the weight ratio of citric acid to silicon dioxide is 1:1.5-3, and the pH value is 2-4; the filler is one or more of microcrystalline cellulose, corn starch, pregelatinized starch, lactose, and mannitol, the disintegrant is one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, pregelatinized starch, cross-linked polyvinyl pyrrolidone, and cross-linked sodium carboxymethyl cellulose, and the binder is one or more of starch, dextrin, and hydroxypropyl cellulose.

[0006] During the production process of the above-mentioned eperisone hydrochloride tablets, citric acid is added to the raw materials to control the content of impurity E in order to improve the stability of the eperisone hydrochloride tablets. However, the results of the stability test showed that the content of impurity E in the eperisone hydrochloride tablets was still higher than that of 0d after being stored at 60°C for 30 days, indicating that the content of impurity E increases with increasing temperature, and there is still a safety risk. At the same time, this method uses citric acid to control the content of impurity E, but does not study the content of impurity D.

[0007] However, the impurity D in the eperisone hydrochloride tablets is a high temperature degradation impurity of eperisone hydrochloride, and its degradation needs to be closely monitored during the preparation process, stability and storage process. Although the impurity D in the eperisone hydrochloride tablets currently purchased on the market meets the requirements of ICH (single impurity ≤ 0.1%). However, the impurity D in the existing eperisone hydrochloride tablets continues to increase during the stability process; at the same time, when the drug reaches the patient, if it is not stored in accordance with the prescribed storage conditions, the impurity D may exceed the limit, seriously affecting the stability of the eperisone hydrochloride tablets, and thus greatly affecting the safety and effectiveness of the patient's medication. Summary of the invention

[0008] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art, provide a pharmaceutical composition containing eperisone hydrochloride and a preparation method thereof which can effectively control the content of impurity D, and effectively improve the stability of the pharmaceutical composition containing eperisone hydrochloride.

[0009] The technical solution adopted by the present invention to solve the technical problem is: a pharmaceutical composition containing eperisone hydrochloride which can effectively control the content of impurity D, comprising eperisone hydrochloride, a filler, a binder, a disintegrant and a lubricant, wherein the pharmaceutical composition also comprises hydrochloric acid, and the hydrochloric acid can inhibit the degradation of eperisone hydrochloride in the pharmaceutical composition containing eperisone hydrochloride into impurity D, wherein the molecular formula of the impurity D is as follows:

[0010]

[0011] Furthermore, the content of impurity D in the pharmaceutical composition containing eperisone hydrochloride is 0 under accelerated stability conditions of a temperature of 60° C. and a time of 30 days.

[0012] Furthermore, in the pharmaceutical composition containing eperisone hydrochloride, the mass percentage of hydrochloric acid is 0.1-5%.

[0013] Preferably, in the pharmaceutical composition containing eperisone hydrochloride, the mass percentage of hydrochloric acid is 1.5%.

[0014] Furthermore, the pH of the pharmaceutical composition containing eperisone hydrochloride is 3.8-4.2.

[0015] Further, the filler is at least one of dextrin, starch, cyclodextrin, and microcrystalline cellulose;

[0016] Further, the binder is at least one of hydroxypropyl cellulose and hydroxypropyl methyl cellulose;

[0017] Furthermore, the disintegrant is at least one of cross-linked polyvinylpyrrolidone, carboxymethyl cellulose, and cross-linked carboxymethyl cellulose sodium;

[0018] Furthermore, the lubricant is one or more of magnesium stearate, calcium stearate, and talc.

[0019] Furthermore, the pharmaceutical composition containing eperisone hydrochloride comprises, by mass percentage, 62.5% of eperisone hydrochloride, 18% of starch, 10% of microcrystalline cellulose, 3% of cross-linked polyvinylpyrrolidone, 4% of hydroxypropyl cellulose, 1% of magnesium stearate, and 1.5% of hydrochloric acid.

[0020] Furthermore, the pharmaceutical composition containing eperisone hydrochloride is eperisone hydrochloride tablets or eperisone hydrochloride capsules.

[0021] The present invention also provides a method for preparing a pharmaceutical composition containing eperisone hydrochloride, which can effectively control the content of impurity D, comprising the following steps:

[0022] 1) Pretreatment of raw materials; 2) Weighing each raw material according to the weight percentage of each raw material, and at the same time dividing the weighed adhesive into two parts according to 1% and 99% of its weight; 3) Preparing adhesive solution: taking one part of the adhesive with a weight percentage of 1% and slowly adding it to the water under stirring, fully swelling, adding hydrochloric acid after visually observing that the hydroxypropyl cellulose is completely dissolved, continuing to stir and dissolve completely, and set aside; 4) Premixing: taking another part of the adhesive with a weight percentage of 99% and eperisone hydrochloride, filler, and disintegrant, adding them to the wet granulation pot, covering the wet granulation pot with a lid, and stirring and mixing; 5) Making soft material: adding the adhesive solution to the wet granulation pot and mixing the materials thoroughly to obtain a soft material; 6) Wet granulation; 7) Drying; 8) Dry granulation; 9) Total mixing: adding a lubricant to the granules obtained by dry granulation treatment and mixing them evenly; 10) Tableting; 11) Coating.

[0023] Furthermore, during the drying process in the step, the temperature of the particles does not exceed 80° C. During the drying process, samples are taken from time to time to measure the moisture content of the particles. When the moisture content of the particles is within 5.0%, the drying is terminated.

[0024] The beneficial effects of the pharmaceutical composition containing eperisone hydrochloride and the preparation method thereof which can effectively control the content of impurity D of the present invention are as follows:

[0025] The preparation process of the invention is simple. By adding hydrochloric acid to the raw materials prepared by the invention, the hydrochloric acid can be used as a pH regulator and can effectively inhibit the degradation of eperisone hydrochloride in the pharmaceutical composition into impurity D. Not only can the content of impurity D in the prepared pharmaceutical composition be 0, but also the impurity D is still not detected under high temperature conditions. The stability of the pharmaceutical composition containing eperisone hydrochloride can be greatly improved, the storage environment of the pharmaceutical composition is widened, and the phenomenon of reduced safety and effectiveness of the drug due to excessive impurity D due to improper storage after the drug reaches the hands of the patient is avoided. The impurity level of the pharmaceutical composition is better controlled, the product quality is also better, the safety for patients is higher, and the safety and effectiveness of the drug composition are greatly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 —A chromatogram showing the content of impurity D detected at 0d in a high temperature stability test of the pharmaceutical composition prepared in Example 1;

[0027] Figure 2 —A chromatogram showing the content of impurity D detected at 30 days in a high temperature stability test of the pharmaceutical composition prepared in Example 1;

[0028] Figure 3 —A chromatogram showing the detection of impurity D content at 60 days in a high temperature stability test of the pharmaceutical composition prepared in Example 1. DETAILED DESCRIPTION

[0029] The present invention is further described below in conjunction with the accompanying drawings and examples, but these specific implementation schemes do not limit the protection scope of the present invention in any way.

[0030] Example 1

[0031] A pharmaceutical composition containing eperisone hydrochloride and capable of effectively controlling the content of impurity D, comprising the raw materials and their mass percentages in the following table, and the pH value of the pharmaceutical composition is 3.8-4.2.

[0032] Raw material name Percentage content (%) Eperisone Hydrochloride 62.5 starch 18 Microcrystalline Cellulose 10 Crospovidone 3 Hydroxypropyl methylcellulose 4 Magnesium Stearate 1 hydrochloric acid 1.5 total 100

[0033] The preparation method of the pharmaceutical composition is:

[0034] 1) Pretreatment: Pass the API (epirisone hydrochloride) and excipients (starch, microcrystalline cellulose, crospovidone, hypromellose, magnesium stearate, hydrochloric acid) through a 50-mesh sieve for later use;

[0035] 2) Weighing: Accurately weigh the raw and auxiliary materials according to the weight percentage of each raw material in the above table, and divide the weighed hydroxypropyl methylcellulose into two parts according to 1% and 99% of its weight;

[0036] 3) Preparation of binder solution: slowly add 1% by weight of hydroxypropyl methylcellulose to water under stirring, with the ratio of the weight of water to the weight of the hydroxypropyl methylcellulose being 17, and allow the solution to swell fully. After the hydroxypropyl methylcellulose is visually completely dissolved, add hydrochloric acid, continue stirring until it is completely dissolved, and set aside;

[0037] 4) Premixing: Add another 99% binder by weight, eperisone hydrochloride, starch, microcrystalline cellulose, and cross-linked polyvinylpyrrolidone into the wet granulation pot, cover the wet granulation pot with a lid, set the stirring, cutting, and mixing times, and start mixing evenly;

[0038] 5) Making soft material: Add the binder solution into the wet granulation pot and mix it with other materials in the pot to make the soft material;

[0039] 6) Wet granulation: The prepared soft material is wet granulated using a pulverizer;

[0040] 7) Drying: The wet granules are transferred to a multifunctional granulating and pilling coating machine for drying. During the drying process, the material temperature is controlled not to exceed 80°C. Samples are taken at irregular intervals during the drying process. The moisture content of the granules is measured using a rapid moisture meter. The drying is terminated when the moisture content of the granules is within 5.0%;

[0041] 8) Dry granulation: The dried granules are subjected to dry granulation using a pulverizing and granulating machine;

[0042] 9) Total mixing: After dry granulation, magnesium stearate is added to the granules and mixed in a mixer;

[0043] 10) Tabletting: The mixed materials are tableted using a rotary tablet press. During the tableting process, the tablet appearance, weight and hardness are monitored. The tablet weight is 80 mg ± 5%, the hardness is greater than 30 N, and the tablet appearance should be complete, smooth and without gaps;

[0044] 11) The compressed tablets are coated with a coating weight gain of 3.0% to obtain a pharmaceutical composition.

[0045] Example 2

[0046] A pharmaceutical composition containing eperisone hydrochloride, which can effectively control the content of impurity D, is composed of the raw materials and their mass percentages in the following table:

[0047] Raw material name Percentage content (%) Eperisone Hydrochloride 62.5 starch 18 Microcrystalline Cellulose 11.4 Crospovidone 3 Hydroxypropyl methylcellulose 4 Magnesium Stearate 1 hydrochloric acid 0.1 total 100

[0048] Example 3

[0049] A pharmaceutical composition containing eperisone hydrochloride, which can effectively control the content of impurity D, is composed of the raw materials and their mass percentages in the following table:

[0050] Raw material name Percentage content (%) Eperisone Hydrochloride 62.5 starch 17 Microcrystalline Cellulose 7.5 Crospovidone 3 Hydroxypropyl methylcellulose 4 Magnesium Stearate 1 hydrochloric acid 5 total 100

[0051] Blank control example

[0052] This blank control example adopts a scheme without adding hydrochloric acid to prepare a pharmaceutical composition containing eperisone hydrochloride, and its raw material composition table is as follows:

[0053] Prescription composition Percentage content (%) Eperisone Hydrochloride 62.5 starch 20 Microcrystalline Cellulose 10 Crospovidone 3 Hydroxypropyl methylcellulose 3.5 Magnesium Stearate 1 total 100

[0054] Comparative Example 1

[0055] The difference between this comparative example and Example 1 is that citric acid is used to replace hydrochloric acid. The amount of citric acid added is the same as that of hydrochloric acid in Example 1, and the other raw materials and the corresponding addition amounts and the preparation method are the same as those in Example 1.

[0056] Comparative Example 2

[0057] The difference between this comparative example and Example 1 is that maleic acid is used to replace hydrochloric acid. The amount of maleic acid added is the same as that of hydrochloric acid in Example 1, and other raw materials and corresponding addition amounts and preparation methods are the same as those in Example 1.

[0058] Comparative Example 3

[0059] The difference between this comparative example and Example 1 is that fumaric acid is used to replace hydrochloric acid. The amount of fumaric acid added is the same as that of hydrochloric acid in Example 1, and the other raw materials and the corresponding addition amounts and the preparation method are the same as those in Example 1.

[0060] Comparative Example 4

[0061] The difference between this comparative example and Example 1 is that phosphoric acid is used to replace hydrochloric acid. The amount of phosphoric acid added is the same as the amount of hydrochloric acid added in Example 1, and the other raw materials and the corresponding addition amounts and the preparation method are the same as in Example 1.

[0062] Comparative Example 5

[0063] The difference between this comparative example and Example 1 is that tartaric acid is used to replace hydrochloric acid. The amount of tartaric acid added is the same as the amount of hydrochloric acid added in Example 1, and the other raw materials and the corresponding addition amounts and the preparation method are the same as in Example 1.

[0064] Comparative Example 6

[0065] The difference between this comparative example and Example 1 is that lactic acid is used to replace hydrochloric acid. The amount of lactic acid added, other raw materials and the corresponding addition amounts, and the preparation method are the same as those in Example 1.

[0066] Comparative Example 7

[0067] The difference between this comparative example and Example 1 is that malic acid is used to replace hydrochloric acid. The amount of malic acid added, other raw materials and the corresponding addition amounts, and the preparation method are the same as those in Example 1.

[0068] Experimental Example 1

[0069] In this experimental example, the pharmaceutical composition containing eperisone hydrochloride prepared by Examples 1-3, blank control examples, comparative examples 1-7, reference preparations 1 and 2 was tested for high temperature stability, and the results are shown in Table 1. Reference preparation 1 is the existing eperisone hydrochloride tablets, produced by Eisai (China) Pharmaceutical Co., Ltd., with a batch number of 2204143; Reference preparation 2 is the existing eperisone hydrochloride tablets, produced by Eisai (China) Pharmaceutical Co., Ltd., with a batch number of 2303132. The high temperature stability test is to store at 60°C for 60 days, and sample and detect the content of impurity D in the pharmaceutical composition at 0 days, 30 days and 60 days respectively.

[0070] The chromatogram corresponding to Example 1 is as follows Figure 1-3 shown.

[0071] The detection method of impurity D refers to the high performance liquid chromatography method (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0521). The specific chromatographic conditions and solution preparation methods are as follows:

[0072] Chromatographic column: Waters Symmetry QC18, 250 mm x 4.6 mm x 5.0 pm; column temperature: 35 °C; wavelength: 254 nm; injection volume: 10 uL; flow rate: 1.0 ml / min; mobile phase: 0.1% acetic acid water-ethyl-methanol = 30:60:10; diluent: acetonitrile; running time: 15 min;

[0073] Blank solution (diluent): acetonitrile.

[0074] Impurity D stock solution: Accurately weigh about 25 mg of impurity D and place it in a 100 ml volumetric flask, make up to volume with acetonitrile by ultrasonication, and shake well.

[0075] Impurity D control solution: Measure 1.0 mL of the impurity D stock solution into a 100 mL volumetric flask and dilute with acetonitrile to prepare a 2.5 μg / mL solution.

[0076] Test solution: Accurately weigh about 50 mg of ethylperidone hydrochloride and place it in a 10 mL volumetric flask. Ultrasonicate and shake to volume with acetonitrile. Prepare two parallel portions.

[0077] Table 1 Results of determination of impurity D content in high temperature (60°C) stability test of Examples 1-3, blank control examples, comparative examples 1-7, and reference preparations

[0078]

[0079]

[0080] As can be seen from the above table, the pharmaceutical composition containing eperisone hydrochloride prepared by using hydrochloric acid as one of the auxiliary materials of the present invention has a corresponding impurity D content of 0 at high temperature acceleration for 30 days and 60 days, which can greatly reduce the content of impurity D compared with the existing eperisone hydrochloride tablets (reference preparations 1 and 2) and blank control examples on the market;

[0081] Compared with the blank control example, the content of impurity D in the treatment groups using other acids instead of hydrochloric acid in Comparative Examples 1-7 at 0d, 30d and 60d was lower than that in the blank control group. The reason is that the degradation mechanism of eperisone hydrochloride is as follows:

[0082]

[0083] Since the API itself is in the form of hydrochloride, the H particles present in other acids can inhibit the degradation of the API into impurity D to a certain extent, thereby making the content of impurity D lower than that of the blank control ratio;

[0084] Moreover, the pharmaceutical compositions containing eperisone hydrochloride prepared by using other acids instead of hydrochloric acid in Comparative Examples 1-7 all contained impurity D at 0d, 30d and 60d, while the content in the present application was 0, indicating that under the action of other acids, eperisone hydrochloride was still continuously degraded into impurity D in the high temperature stability experiment, causing the content of impurity D to increase continuously. This is because although other acids can also dissociate H particles, there is reverse dissociation in the dissociation process, and the inhibition is not complete;

[0085] However, the inventors of the present application have found that when hydrochloric acid is used to prepare a pharmaceutical composition containing eperisone hydrochloride, the degradation of eperisone hydrochloride into impurity D can be effectively inhibited, so that the content of impurity D is controlled to 0 in the high temperature stability experiment, and there is no reverse dissociation process in the hydrochloric acid inhibition process, so that the inhibition of impurity D is very thorough, which has achieved unexpected technical effects compared with other acids.

[0086] Experimental Example 2

[0087] This experimental example also uses the same high temperature stability test as in Experimental Example 1 to determine the content of impurity A in the pharmaceutical composition containing eperisone hydrochloride prepared in Example 1. The results are shown in Table 2. The detection method of impurity A is the same as the detection method of impurity D.

[0088] Table 2 Results of determination of impurity A content in high temperature (60°C) stability test of Example 1

[0089]

[0090]

[0091] It can be seen from Table 2 that after adding hydrochloric acid, the content of impurity A can still be detected and remains unchanged, indicating that there are significant differences between the inhibitory effects of hydrochloric acid on different impurities, that is, hydrochloric acid has no inhibitory effect on impurity A, but has a significant inhibitory effect on impurity D.

[0092] Experimental Example 3

[0093] This experimental example refers to the component table of Example 1, and with the help of high temperature stability test, the amount of starch is adjusted to investigate the effect of the addition of hydrochloric acid (0, 0.05%, 0.1%, 1%, 2%, 3%, 4%, 5%, 5.5%, 6%) on the impurity D and disintegration time in the pharmaceutical composition containing eperisone hydrochloride, and the mass percentages of eperisone hydrochloride and other excipients remain unchanged. The high temperature stability test is stored at 60°C for 30 days, and samples are taken at 30 days to detect the content of impurity D in the pharmaceutical composition. The detection method of disintegration time is detected by referring to the Pharmacopoeia General Principles 0921 method.

[0094] Table 3 Effect of hydrochloric acid addition on the content of impurity D and disintegration time in the pharmaceutical composition containing eperisone hydrochloride

[0095]

[0096] As can be seen from the above table, when the amount of hydrochloric acid added is 0.1%, the content of impurity D in the corresponding pharmaceutical composition starts to be 0, and as the amount of addition continues to increase, the content of impurity D remains 0; however, when the amount of addition increases to more than 5%, the disintegration time will increase significantly. Therefore, considering the inhibitory effect of hydrochloric acid on the content of impurity D and the disintegration time, the preferred amount of hydrochloric acid added is 0.1-5%, and the most preferred is 1.5%.

[0097] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of equivalent changes using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition containing eperisone hydrochloride in which the content of impurity D can be effectively controlled, comprising eperisone hydrochloride, a filler, a binder, a disintegrant and a lubricant, characterized in that: The pharmaceutical composition further includes hydrochloric acid, which can inhibit the degradation of eperisone hydrochloride in the pharmaceutical composition containing eperisone hydrochloride into impurity D, and the molecular formula of the impurity D is as follows:

2. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 1, characterized in that: The content of impurity D in the pharmaceutical composition containing eperisone hydrochloride is 0 under accelerated stability conditions of a temperature of 60° C. and a time of 30 days.

3. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 1, characterized in that: In the pharmaceutical composition containing eperisone hydrochloride, the mass percentage of hydrochloric acid is 0.1-5%.

4. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 3, characterized in that: In the pharmaceutical composition containing eperisone hydrochloride, the mass percentage of hydrochloric acid is 1.5%.

5. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 1, characterized in that: The pH of the pharmaceutical composition containing eperisone hydrochloride is 3.8-4.

2.

6. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 1, characterized in that: The filler is at least one of dextrin, starch, cyclodextrin, and microcrystalline cellulose; the binder is at least one of hydroxypropyl cellulose and hydroxypropyl methylcellulose; the disintegrant is at least one of cross-linked polyvinylpyrrolidone, carboxymethyl cellulose, and cross-linked sodium carboxymethyl cellulose; and the lubricant is one or more of magnesium stearate, calcium stearate, and talc.

7. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 6, characterized in that: Calculated by mass percentage, the pharmaceutical composition containing eperisone hydrochloride comprises 62.5% of eperisone hydrochloride, 18% of starch, 10% of microcrystalline cellulose, 3% of cross-linked polyvinylpyrrolidone, 4% of hydroxypropyl cellulose, 1% of magnesium stearate and 1.5% of hydrochloric acid.

8. A pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 1, characterized in that: The pharmaceutical composition containing eperisone hydrochloride is eperisone hydrochloride tablets or eperisone hydrochloride capsules.

9. A method for preparing a pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in any one of claims 1 to 8, characterized in that: The following steps are involved: 1) Pretreatment of raw materials; 2) Weighing each raw material according to the weight percentage of each raw material, and at the same time dividing the weighed adhesive into two parts according to 1% and 99% of its weight; 3) Preparing adhesive solution: taking one part of the adhesive with a weight percentage of 1% and slowly adding it to the water under stirring, fully swelling, adding hydrochloric acid after visually observing that the hydroxypropyl cellulose is completely dissolved, continuing to stir and dissolve completely, and set aside; 4) Premixing: taking another part of the adhesive with a weight percentage of 99% and eperisone hydrochloride, filler, and disintegrant, adding them to the wet granulation pot, covering the wet granulation pot with a lid, and stirring and mixing; 5) Making soft material: adding the adhesive solution to the wet granulation pot and mixing the materials thoroughly to obtain a soft material; 6) Wet granulation; 7) Drying; 8) Dry granulation; 9) Total mixing: adding a lubricant to the granules obtained by dry granulation treatment and mixing them evenly; 10) Tableting; 11) Coating.

10. A method for preparing a pharmaceutical composition containing eperisone hydrochloride with effectively controlled impurity D content as claimed in claim 9, characterized in that: During the drying process in the step, the temperature of the particles does not exceed 80° C. During the drying process, samples are taken from time to time to measure the moisture content of the particles. When the moisture content of the particles is within 5.0%, the drying is terminated.

Images