A Cyclobenzaprine Hydrochloride Sustained Release Capsule and Its Preparation Method

Abstract

The present invention relates to a cyclobenzaprine hydrochloride sustained-release capsule. The content of the sustained-release capsule includes sustained-release coated pellets, and the sustained-release coated pellets are made of blank cores and drug-containing sustained-release coating layers. The drug-containing sustained-release coating layer includes cyclobenzaprine hydrochloride and a sustained-release material. The coating solvent used in the coating process of the sustained-release coated pellets does not contain ethanol or water. The cyclobenzaprine hydrochloride sustained-release capsule prepared by the present invention not only has a similar in vitro release rate to the original research formulation, but also has good chemical stability, ensuring the safety and effectiveness of clinical medication.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and particularly to a cyclobenzaprine hydrochloride sustained-release capsule. Background Art

[0002] Cyclobenzaprine hydrochloride, chemically named 5-(3-dimethylaminopropene)dibenzo[a,e]cycloheptatriene hydrochloride, is a tricyclic muscle relaxant developed by Merck & Co., Inc. It was approved for marketing in more than a dozen countries such as the United States in the 1980s. Clinically, it is mainly used to treat discomfort of the skeletal muscle system or muscle spasms accompanied by pain symptoms (including pain, tenderness, movement limitation, daily activity limitation, etc.). However, due to the short half-life of cyclobenzaprine hydrochloride in vivo, its conventional dosage form needs to be taken 3 times a day, with relatively frequent medication, which affects the compliance of patients with medication.

[0003] The cyclobenzaprine hydrochloride sustained-release pellet capsule is a sustained-release preparation first developed successfully by Anesta Pharmaceuticals in the United States and was approved for marketing in the United States in February 2007. The trade name is The marketed specifications include 15 mg and 30 mg, and only one dose per day is required to maintain the blood drug concentration for 24 hours. This sustained-release preparation significantly improves the compliance of patients with medication. The imitation development of the cyclobenzaprine hydrochloride sustained-release pellet capsule has good market prospects.

[0004] The prior art CN114432266A discloses a cyclobenzaprine hydrochloride sustained-release capsule. The content of the capsule includes sustained-release coated pellets and a lubricant. The sustained-release coated pellets contain cyclobenzaprine hydrochloride, blank pellet cores, a sustained-release material, and a stabilizer. The coating solvent used for coating the sustained-release pellets is ethanol. However, it is found in the research that the sustained-release capsules obtained by using ethanol as the coating solvent are prone to problems inconsistent with the in vitro release of the original preparation. In addition, if an aqueous solvent is added when preparing the coating solution, water is likely to remain in the drug-containing coating layer after the sustained-release pellets are coated by fluidized bed, which is not conducive to the chemical stability of the active pharmaceutical ingredient during long-term storage.

[0005] At present, there is no relevant report on a generic drug of cyclobenzaprine hydrochloride sustained-release capsule that has both in vitro release consistent with the original preparation and good chemical stability and does not contain a stabilizer. Summary of the Invention

[0006] The purpose of the present invention is to provide a cyclobenzaprine hydrochloride sustained-release capsule with in vitro release similar to the original preparation, good chemical stability, and simple preparation process.

[0007] To solve the above technical problems, a first aspect of the present invention provides a cyclobenzaprine hydrochloride sustained-release capsule. The content of the sustained-release capsule includes sustained-release coated pellets, and the sustained-release coated pellets are made of blank pellet cores and drug-containing sustained-release coating layers. The drug-containing sustained-release coating layer includes cyclobenzaprine hydrochloride and a sustained-release material, and the coating solvent used in the coating process of the sustained-release coated pellets does not contain ethanol or water.

[0008] Preferably, the coating solvent is selected from one or more of isopropanol, n-propanol, n-butanol, and tert-butanol. More preferably, the coating solvent is selected from one or more of isopropanol and n-propanol. Further preferably, the coating solvent is isopropanol.

[0009] Preferably, the sustained-release material is selected from one or more of ethyl cellulose and acrylic resin. More preferably, the sustained-release material is ethyl cellulose. Further preferably, the sustained-release material is ethyl cellulose with a viscosity of 18 - 24 mPa·s.

[0010] Preferably, the blank pellet core is a sucrose pellet core.

[0011] Preferably, the content of the sustained-release capsule further includes a lubricant.

[0012] Preferably, the lubricant is selected from one or more of magnesium stearate, calcium stearate, stearic acid, silicon dioxide, talc powder, and glyceryl behenate. More preferably, the lubricant is selected from one or more of magnesium stearate, silicon dioxide, and talc powder. Further preferably, the lubricant is talc powder.

[0013] Preferably, the sustained-release coating layer further includes a plasticizer.

[0014] Preferably, the plasticizer is selected from one or more of triethyl citrate, dibutyl phthalate, or glyceryl triacetate. More preferably, the plasticizer is selected from one or more of triethyl citrate or dibutyl phthalate. Further preferably, the plasticizer is triethyl citrate.

[0015] Preferably, the coating layer does not contain a stabilizer. More preferably, the stabilizer is selected from one or more substances such as antioxidants, edetic acid and its salts, and glyceryl monostearate. Further preferably, the antioxidants are selected from one or more of vitamin C, vitamin E, and sulfites, and the edetic acid salts are selected from one or more of disodium edetate, dipotassium edetate, calcium disodium edetate, sodium edetate, and trisodium edetate.

[0016] Preferably, the weight of cyclobenzaprine hydrochloride accounts for 15-35% of the content of the sustained-release capsule. More preferably, the weight of cyclobenzaprine hydrochloride accounts for 18-30% of the content of the sustained-release capsule. Further preferably, the weight of cyclobenzaprine hydrochloride accounts for 21.2-26.4% of the content of the sustained-release capsule.

[0017] Preferably, the weight of the blank pellets accounts for 20-45% of the content of the sustained-release capsule. More preferably, the weight of the blank pellets accounts for 25-40% of the content of the sustained-release capsule. Further preferably, the weight of the blank pellets accounts for 33-35.4% of the content of the sustained-release capsule.

[0018] Preferably, the weight of the sustained-release material accounts for 30-55% of the content of the sustained-release capsule. More preferably, the weight of the sustained-release material accounts for 30-45% of the content of the sustained-release capsule. Further preferably, the weight of the sustained-release material accounts for 35.4-39.6% of the content of the sustained-release capsule.

[0019] Preferably, the weight percentage of the sustained-release material in the coating solution is 2-10%; more preferably, the weight percentage of the sustained-release material in the coating solution is 4-8%; further preferably, the weight percentage of the sustained-release material in the coating solution is 6%.

[0020] Preferably, the weight of the lubricant accounts for 0.1-2% of the content of the sustained-release capsule. More preferably, the weight of the lubricant accounts for 0.3-1.5% of the content of the sustained-release capsule. Further preferably, the weight of the lubricant accounts for 0.5-1% of the content of the sustained-release capsule.

[0021] Preferably, the weight of the plasticizer accounts for 3-10% of the content of the sustained-release capsule. More preferably, the weight of the plasticizer accounts for 5-8% of the content of the sustained-release capsule. Further preferably, the weight of the plasticizer accounts for 7% of the content of the sustained-release capsule.

[0022] Preferably, the content of the sustained-release capsule comprises the following components by weight percentage: 26.4% of cyclobenzaprine hydrochloride, 33% of sucrose pellets, 39.6% of ethylcellulose and 1% of talc.

[0023] Preferably, the content of the sustained-release capsule comprises the following components by weight percentage: 21.2% of cyclobenzaprine hydrochloride, 35.4% of sucrose pellets, 35.4% of ethylcellulose, 7% of triethyl citrate and 1% of talc.

[0024] Preferably, the content of the sustained-release capsule comprises the following components by weight percentage: 18.6% of cyclobenzaprine hydrochloride, 24.7% of sucrose pellets, 55.7% of ethylcellulose and 1% of talc.

[0025] Preferably, the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsule and the original developed formulation Amrix is greater than 50. More preferably, the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsule and the original developed formulation Amrix is greater than 55. Further preferably, the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsule and the original developed formulation Amrix is greater than 60.

[0026] Preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when stored at 40°C and RH75% for 1 month. More preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when stored at 40°C and RH75% for 2 months. Further preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when stored at 40°C and RH75% for 3 months.

[0027] The second aspect of the present invention provides a method for preparing the above-mentioned cyclobenzaprine hydrochloride sustained-release capsule, comprising the following steps:

[0028] (1) Dissolve the prescribed amount of cyclobenzaprine hydrochloride, sustained-release material and optional plasticizer in a coating solvent to prepare a coating solution;

[0029] (2) Slowly spray the coating solution prepared in step (1) onto blank pellets in a fluidized bed coater to prepare sustained-release coated pellets;

[0030] (3) Mix the sustained-release coated pellets with an optional lubricant, and fill into capsules to obtain the product;

[0031] The coating solvent used in step (1) does not contain ethanol or water.

[0032] Preferably, the coating solvent is selected from one or more of isopropyl alcohol, n-propyl alcohol, n-butyl alcohol, and tert-butyl alcohol. More preferably, the coating solvent is selected from one or more of isopropyl alcohol and n-propyl alcohol. Further preferably, the coating solvent is isopropyl alcohol.

[0033] Preferably, the parameters of the fluidized bed coating in step (2) are as follows: inlet air temperature is 35 - 45°C, material temperature is 30 - 40°C, outlet air temperature is 25 - 35°C, atomization pressure is 1.0 - 3.0 bar, air volume is 100 - 300 cfm, humidity is 10 - 40%, and flow rate is 5 - 30 g / min.

[0034] More preferably, the parameters of the fluidized bed coating in step (2) are as follows: inlet air temperature is 40°C, material temperature is 32°C, outlet air temperature is 31°C, atomization pressure is 1.5 bar, air volume is 100 cfm, humidity is 20%, and flow rate is 21 g / min.

[0035] The third aspect of the present invention provides the use of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules in the medicine for relieving local muscle spasm and its accompanying symptoms.

[0036] Preferably, the accompanying symptoms are pain, tenderness, limited mobility, and restriction of daily living behaviors.

[0037] The fourth aspect of the present invention provides the use of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules in the preparation of a muscle relaxant.

[0038] The fifth aspect of the present invention provides the use of a coating solvent in improving the in vitro release rate and / or chemical stability of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules, and the coating solvent does not contain ethanol or water.

[0039] Furthermore, the present invention provides the use of a coating solvent in simultaneously improving the in vitro release rate and chemical stability of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules, and the coating solvent does not contain ethanol or water.

[0040] Preferably, the coating solvent is selected from one or more of isopropanol, n-propanol, n-butanol, and tert-butanol. More preferably, the coating solvent is selected from one or more of isopropanol and n-propanol. Further preferably, the coating solvent is isopropanol.

[0041] Preferably, the improvement of the in vitro release rate of the cyclobenzaprine hydrochloride sustained-release capsules means that the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsules and the original developed formulation Amrix is greater than 50. More preferably, the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsules and the original developed formulation Amrix is greater than 55. Further preferably, the similarity factor f2 value of the cyclobenzaprine hydrochloride sustained-release capsules and the original developed formulation Amrix is greater than 60.

[0042] Preferably, the improvement of the chemical stability of the cyclobenzaprine hydrochloride sustained-release capsules means that the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsules is less than 0.05% when placed at 40°C and RH75% for 1 month. More preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsules is less than 0.05% when placed at 40°C and RH75% for 2 months. Further preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsules is less than 0.05% when placed at 40°C and RH75% for 3 months.

[0043] The sixth aspect of the present invention provides the use of a coating solution in improving the in vitro release rate and / or chemical stability of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules, and the coating solution contains cyclobenzaprine hydrochloride, a sustained-release material, and a coating solvent, and the coating solvent does not contain ethanol or water.

[0044] Preferably, the present invention provides the use of a coating solution in simultaneously improving the in vitro release rate and chemical stability of the above-mentioned cyclobenzaprine hydrochloride sustained-release capsules.

[0045] Preferably, the coating solvent is selected from one or more of isopropyl alcohol, n-propanol, n-butanol, and tert-butanol. More preferably, the coating solvent is selected from one or more of isopropyl alcohol and n-propanol. Further preferably, the coating solvent is isopropyl alcohol.

[0046] Preferably, the coating solution does not contain a stabilizer. More preferably, the stabilizer is selected from one or more of antioxidants, edetic acid and its salts, and glyceryl monostearate. Further preferably, the antioxidant is selected from one or more of vitamin C, vitamin E, and sulfites, and the edetic acid salts are selected from one or more of disodium edetate, dipotassium edetate, calcium disodium edetate, sodium edetate, and trisodium edetate.

[0047] Preferably, the weight of cyclobenzaprine hydrochloride accounts for 15-35% of the content of the sustained-release capsule. More preferably, the weight of cyclobenzaprine hydrochloride accounts for 18-30% of the content of the sustained-release capsule. Further preferably, the weight of cyclobenzaprine hydrochloride accounts for 21.2-26.4% of the content of the sustained-release capsule.

[0048] Preferably, the weight of the sustained-release material accounts for 30-55% of the content of the sustained-release capsule. More preferably, the weight of the sustained-release material accounts for 30-45% of the content of the sustained-release capsule. Further preferably, the weight of the sustained-release material accounts for 35.4-39.6% of the content of the sustained-release capsule.

[0049] Preferably, the in vitro release rate of the improved cyclobenzaprine hydrochloride sustained-release capsule is such that the similarity factor f2 value between the cyclobenzaprine hydrochloride sustained-release capsule and the original research formulation Amrix is greater than 50. More preferably, the similarity factor f2 value between the cyclobenzaprine hydrochloride sustained-release capsule and the original research formulation Amrix is greater than 55. Further preferably, the similarity factor f2 value between the cyclobenzaprine hydrochloride sustained-release capsule and the original research formulation Amrix is greater than 60.

[0050] Preferably, the chemical stability of the improved cyclobenzaprine hydrochloride sustained-release capsule is such that the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when placed at 40°C and RH75% for 1 month. More preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when placed at 40°C and RH75% for 2 months. Further preferably, the total impurity content of the cyclobenzaprine hydrochloride sustained-release capsule is less than 0.05% when placed at 40°C and RH75% for 3 months.

[0051] The technical effects produced by the present invention:

[0052] 1. The present invention unexpectedly discovers that after directly encapsulating a specific organic solvent (such as isopropanol), cyclobenzaprine hydrochloride, and a sustained-release material in a blank pill core, the prepared cyclobenzaprine hydrochloride sustained-release capsule not only has an in vitro release rate similar to that of the original developed preparation, but also has good chemical stability without containing a stabilizer. After long-term storage at 40 °C and RH 75%, the total amount of impurities is still less than 0.05%, ensuring the safety and effectiveness of clinical medication.

[0053] 2. The preparation process of the cyclobenzaprine hydrochloride sustained-release capsule provided by the present invention adopts one-step coating of the active ingredient and the sustained-release material, with a simple production process and a short process time. Detailed Embodiments

[0054] The following details the embodiments of the present invention. These embodiments are implemented on the premise of the technical solution of the present invention, providing detailed implementation manners and specific operation processes. However, the protection scope of the present invention is not limited to the following embodiments.

[0055] Test Example 1: Influence of Coating Solvent on In Vitro Release Rate of Cyclobenzaprine Hydrochloride Sustained-Release Capsule

[0056] 1. Test Method

[0057] 1.1 Preparation of Sustained-Release Capsule

[0058] (1) Prescription

[0059] The prescriptions of Examples 1 - 3 of the present invention are shown in the following table (unit dose is 30 mg).

[0060]

[0061] a: Volatilizes during the coating process.

[0062] The prescriptions of Comparative Examples 1 - 3 of the present invention are shown in the following table (unit dose is 30 mg).

[0063]

[0064]

[0065] a: Volatilizes during the coating process.

[0066] (2) Preparation Process

[0067] The preparation methods of Examples 1-3 and Comparative Examples 1-3 are as follows: (1) Add the prescribed amounts of cyclobenzaprine hydrochloride, ethylcellulose, and optionally triethyl citrate to the coating solvent (isopropanol or ethanol), and the weight percentage of ethylcellulose in the coating solution is 6%; (2) Place the prescribed amount of sucrose cores in a fluidized bed coater; (3) Set the parameters of the fluidized bed: the inlet air temperature is 40°C, the material temperature is 32°C, the outlet air temperature is 31°C, the atomization pressure is 1.5 bar, the air volume is 100 cfm, the humidity is 20%, and the flow rate is 21 g / min. Slowly spray the coating solution prepared in step (1) into the fluidized bed to coat the sucrose cores with a drug-containing sustained-release layer; (4) After the coating is completed, discharge the material. Mix the sucrose cores coated with the drug-containing sustained-release layer with talc powder, and then fill them into capsules (the unit dose of the capsule is 30 mg) to obtain the product.

[0068] 1.2 In vitro release rate detection

[0069] Perform in vitro release rate tests on the cyclobenzaprine hydrochloride sustained-release capsules prepared in Examples 1-2 and Comparative Examples 1-3, as well as the original research reference preparation Amrix (30 mg specification). The specific release rate determination method is as follows: paddle method, the rotation speed is 50 rpm, the test solution is 0.1 N hydrochloric acid, 900 ml, the test temperature is 37 ± 0.5°C, and the in vitro release rates at the 1st, 2nd, 4th, 8th, 12th, and 16th hours are measured, and the cumulative release percentages at each time point are calculated.

[0070] The similarity factor (f2) is a parameter for measuring the similarity of two dissolution curves, and the calculation formula is as follows:

[0071] f2 = 50log[[1 + 1 / nΣ(R t -T t ) 2 -0.5 ×100]

[0072] In the formula, R t is the cumulative drug release percentage of the reference preparation at time t; T t is the cumulative drug release percentage of the test preparation at time t; n is the number of sampling points. When the two drug release curves completely coincide, f2 is 100; when the difference between the two curves increases, the f2 value decreases. Generally, it is stipulated that when the f2 value is between 50 and 100, it can be considered that the drug release of the two prescription preparations is not different under the same drug release conditions.

[0073] 2 Test results

[0074] The in vitro release rate results of the sustained-release capsules of Examples 1-2 and Comparative Examples 1-3 at different time points are shown in Table 1 below.

[0075] Table 1 In vitro release rates (%) of Examples 1-2 and Comparative Examples 1-3 of the present invention at each time point ​

[0076] Time Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Reference Preparation 1h 15 17 93 92 24 7 2h 25 26 93 92 33 28 4h 45 43 94 93 55 52 8h 67 72 93 93 73 70 12h 73 81 94 93 79 78 16h 76 86 94 94 84 83 f2 61 61 16 16 56 —

[0077] As can be seen from the in vitro release results in Table 1 above, for Comparative Examples 1-2 with ethanol as the coating solvent, the similarity factor of their release rate is less than 50 compared with the reference preparation, indicating that the in vitro dissolution behaviors of Comparative Examples 1 and 2 are not similar to that of the reference preparation. However, for Examples 1-2 with isopropanol as the coating solvent, the similarity factor with the reference preparation is greater than 60, indicating that after using isopropanol instead of ethanol, the in vitro release rate of the cyclobenzaprine hydrochloride sustained-release capsule can be significantly improved.

[0078] Test Example 2. Influence of Coating Solvent on the Impurity Content of Cyclobenzaprine Hydrochloride Sustained-Release Capsule

[0079] 1. Test Method

[0080] The cyclobenzaprine hydrochloride sustained-release capsules of Examples 1-3 and Comparative Example 3 were placed under the conditions of 40 °C and RH 75%, and samples were taken at the 0th, 1st, 2nd, and 3rd months respectively to investigate the generation of the total amount of impurities in the sustained-release capsules at different sampling times. The self-control method was used to calculate the percentage (%) of the total amount of impurities in the total weight of the active drug.

[0081] The sample treatment method is as follows: Weigh an appropriate amount of the content of the cyclobenzaprine hydrochloride sustained-release capsule, place it in a volumetric flask, add methanol with a volume of 60% of the volumetric flask, place the volumetric flask on a shaker and shake or ultrasonicate to completely disintegrate the pellets in the sustained-release capsule. Then add water with a volume of 20% of the volumetric flask, ultrasonicate for another 15 minutes, cool to room temperature, and make up the volume to the scale with water and mix well. Transfer a part of the test solution through a filter membrane, and take the subsequent filtrate for injection analysis.

[0082] The HPLC chromatographic conditions for sample detection are as follows: Mobile phase A: pH 6.2 buffer salt: methanol = 48:52 (V / V); Mobile phase B: pH 6.2 buffer salt: acetonitrile = 48:52 (V / V); The chromatographic column is filled with octadecylsilane-bonded silica gel; The detection wavelength is UV 239 nm; The column temperature is 45 °C; The injection volume is 10 μL; The flow rate is 1.2 ml / minute, and the mobile phase is linearly gradient eluted as shown in the following table:

[0083]

[0084]

[0085] 2. Test Results

[0086] The measurement results of the total amount of impurities in the sustained-release capsules of Examples 1-3 and Comparative Example 3 at different time points are shown in Table 2 below.

[0087] Table 2 Total Amount of Impurities (%) of Examples 1-3 and Comparative Example 3 of the Present Invention at Different Time Points

[0088] Sampling Time Example 1 Example 2 Example 3 Comparative Example 3 0 months <0.05 <0.05 <0.05 0.2 1 month <0.05 <0.05 <0.05 1.0 2 months <0.05 <0.05 <0.05 — 3 months <0.05 <0.05 <0.05 —

[0089] Note: “—” indicates that the total impurity measurement at the previous sampling point was too high, resulting in the discontinuation of the total impurity measurement at this sampling point.

[0090] Combining Table 1 and Table 2, it can be seen that Comparative Example 3 (high-content ethylcellulose formulation) with ethanol as the coating solvent has a dissolution behavior in vitro similar to that of the reference preparation. However, the impurity content after 2 months is greater than 1.0%, proving that although the sustained-release capsule with ethanol as the coating solvent can solve the problem of in vitro release rate by increasing the content of ethylcellulose, it still has storage stability problems. Therefore, ethanol is not suitable as the coating solvent for the cyclobenzaprine hydrochloride sustained-release capsule.

[0091] In contrast, for Examples 1-3 with isopropanol as the coating solvent, the total impurity content is still less than 0.05% after being placed at 40 °C and RH 75% for 3 months, proving that the cyclobenzaprine hydrochloride sustained-release capsule prepared by the present invention with isopropanol as the coating solvent has excellent chemical stability.

[0092] Although specific embodiments of the present invention have been described, those skilled in the art should recognize that various changes and modifications can be made to the present invention without departing from the scope or spirit of the present invention. Therefore, the present invention is intended to cover all such changes and modifications that fall within the scope of the appended claims and their equivalents.

Claims

1. A cyclobenzaprine hydrochloride sustained-release capsule, characterized in that, The content of the sustained-release capsule includes sustained-release coated pellets, which are made of blank cores and drug-containing sustained-release coating layers. The drug-containing sustained-release coating layer includes cyclobenzaprine hydrochloride and a sustained-release material. The sustained-release material is ethyl cellulose. The coating solvent used in the coating process of the sustained-release coated pellets is isopropanol. The weight of cyclobenzaprine hydrochloride accounts for 18 - 30% of the content of the sustained-release capsule, the weight of the blank cores accounts for 25 - 40% of the content of the sustained-release capsule, and the weight of the sustained-release material accounts for 30 - 45% of the content of the sustained-release capsule.

2. The cyclobenzaprine hydrochloride sustained-release capsule according to claim 1, wherein The weight of cyclobenzaprine hydrochloride accounts for 21.2 - 26.4% of the content of the sustained-release capsule, the weight of the blank cores accounts for 33 - 35.4% of the content of the sustained-release capsule, and the weight of the sustained-release material accounts for 35.4 - 39.6% of the content of the sustained-release capsule.

3. The cyclobenzaprine hydrochloride sustained-release capsule according to claim 1, wherein The blank cores are sucrose cores.

4. The cyclobenzaprine hydrochloride sustained-release capsule according to claim 1, wherein The content of the sustained-release capsule further includes a lubricant.

5. The cyclobenzaprine hydrochloride sustained-release capsule according to claim 1, wherein The sustained-release coating layer further includes a plasticizer.

6. The preparation method of the cyclobenzaprine hydrochloride sustained-release capsule according to any one of claims 1-5, characterized in that, It includes the following steps: (1) Dissolve the prescribed amount of cyclobenzaprine hydrochloride, the sustained-release material, and an optional plasticizer in the coating solvent to prepare a coating solution; (2) Slowly spray the coating solution prepared in step (1) onto the blank cores in a fluidized bed coater to prepare the sustained-release coated pellets; (3) Mix the sustained-release coated pellets with an optional lubricant, fill them into capsules, and obtain the product; The coating solvent used in step (1) is isopropanol.

7. Use of the cyclobenzaprine hydrochloride sustained-release capsule according to any one of claims 1 - 5 in the preparation of a drug for relieving local muscle spasm and its accompanying symptoms.

8. Use of a coating solvent in improving the in vitro release rate and / or chemical stability of the cyclobenzaprine hydrochloride sustained-release capsules according to any one of claims 1-5, characterized in that The coating solvent is isopropanol.

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