Diclofenac sodium sustained release tablet and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and relates to a diclofenac sodium sustained release tablet and a preparation method thereof. The diclofenac sodium sustained-release tablet is prepared from diclofenac sodium, an ellagic acid-shellac-chitosan sustained-release material, a filling agent, a lubricating agent and an adhesive. According to the invention, a sustained-release material is prepared through solution preparation, film formation and post-treatment, and then the sustained-release tablet is prepared by adopting a wet granulation and tabletting method. Experiments show that the diclofenac sodium sustained-release tablet is good in stability, the content of diclofenac sodium basically remains unchanged after 6 months of an acceleration test, the sustained-release effect is ideal, the effective concentration maintaining time of a medicine in a body can be effectively prolonged, the medicine taking frequency is reduced, and the diclofenac sodium sustained-release tablet has good process feasibility and industrial production prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a diclofenac sodium sustained-release tablet and a preparation method thereof. Background Art

[0002] Diclofenac sodium is a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase (COX) activity and reduces prostaglandin synthesis, thereby alleviating inflammatory responses and pain. It is widely used clinically to alleviate acute attacks or persistent joint swelling and pain in various chronic arthritis conditions, such as rheumatoid arthritis and osteoarthritis, as well as various soft tissue rheumatic pains and acute mild to moderate pain. However, diclofenac sodium is highly hygroscopic, which causes it to readily absorb moisture from the environment during storage. This not only alters the drug's physical form, such as agglomeration and deliquescence, but can also trigger chemical reactions, affecting the drug's chemical stability and reducing the content of its active ingredient, thereby impacting the efficacy and safety of the formulation.

[0003] Currently, preparing diclofenac sodium into a sustained-release formulation is an important means to prolong the drug's duration of action, reduce the frequency of medication, and improve patient compliance. However, due to its hygroscopicity, the preparation process of sustained-release formulations can easily lead to uneven mixing of excipients and the drug, affecting the sustained-release effect, resulting in an unstable drug release rate and difficulty achieving the desired sustained-release effect.

[0004] Chinese patent publication number CN102188388A discloses a diclofenac sodium sustained-release micropellet preparation. The diclofenac sodium sustained-release micropellet mainly consists of two parts: blank micropellets and a drug sustained-release composite layer. The sustained-release material is selected from one or a combination of acrylic resin, hydroxypropyl methylcellulose, ethyl cellulose, stearic acid or shellac.

[0005] Chinese patent publication number CN110101686A discloses a diclofenac sodium sustained-release capsule comprising diclofenac sodium, excipients, a coating component, a wetting agent, a surfactant, a plasticizer, and a sunscreen. The dressing includes sucrose, corn starch, polyethylene glycol 6000, aminomethacrylate copolymer type A, talc, lactose, Tween 80, purified water, 96% ethanol, and acetone. The capsule shell comprises gelatin, titanium dioxide, shellac glaze, polyethylene glycol, and black iron oxide.

[0006] Existing diclofenac sodium sustained-release formulations often address sustained-release issues by simply adjusting excipients or processes, failing to fundamentally address the impact of hygroscopicity on formulation stability and sustained-release efficacy. Therefore, there is an urgent need to develop a diclofenac sodium sustained-release tablet and its preparation method that can effectively overcome diclofenac sodium's hygroscopicity while simultaneously improving formulation stability and sustained-release efficacy. Summary of the Invention

[0007] Based on this, the present invention focuses on developing a formulation that combines strong stability, controllable sustained-release properties, and simplified processing. Through innovative excipient systems and the functional application of ellagic acid, this approach systematically addresses these technical bottlenecks. Specifically, the present invention provides a diclofenac sodium sustained-release tablet with ellagic acid-shellac-chitosan sustained-release material as the key ingredient.

[0008] The diclofenac sodium sustained-release tablets comprise, by weight, 25 to 100 parts of diclofenac sodium, 10 to 40 parts of ellagic acid-shellac-chitosan sustained-release material, 58 to 260 parts of filler, 0.1 to 2 parts of lubricant, and 5 to 20 parts of binder. The preparation method of the ellagic acid-shellac-chitosan sustained-release material is as follows:

[0009] (1) Solution preparation: Dissolve 20 g of chitosan in 2% (v / v) acetic acid solution to prepare a 2% chitosan solution; dissolve 30 g of shellac in 95% ethanol solution and heat in a 60°C water bath to prepare a 5% shellac ethanol solution; dissolve 10 g of ellagic acid (CAS: 476-66-4, purity 95%) in a small amount of dimethyl sulfoxide by ultrasonication, then add the chitosan solution and stir evenly.

[0010] (2) Film formation: Under stirring conditions, add the shellac ethanol solution to the chitosan solution containing ellagic acid, stir for 30 minutes, and then pour it into a mold. Volatilize the solvent at room temperature, and then dry it in a drying oven at 45°C for 24 hours to form a film.

[0011] (3) Post-treatment: The film was removed and rinsed with deionized water, and dried in a vacuum drying oven at 35°C to a constant weight to obtain the ellagic acid-shellac-chitosan sustained-release material.

[0012] Diclofenac sodium sustained-release tablets are prepared using a wet granulation and tableting process, which includes mixing, granulation, drying, granulation, blending, and tableting. Specifically, diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powders, and fillers are uniformly mixed; a binder solution of appropriate concentration is prepared as a soft material, which is then sieved to form wet granules; the wet granules are dried, granulated, and uniformly blended with a lubricant before tableting.

[0013] At the same time, the present invention also provides a plurality of comparative examples, respectively using shellac-chitosan sustained-release material, ellagic acid-peach gum-chitosan sustained-release material, ellagic acid-shellac sustained-release material, different proportions of ellagic acid-shellac-chitosan sustained-release material, gallic acid-shellac-chitosan sustained-release material to prepare diclofenac sodium sustained-release tablets, so as to compare and verify the advantages of the solution of the present invention.

[0014] It should be noted that, based on the diclofenac sodium sustained-release tablets of the present invention, the plain tablets can also be coated. The coating layer can select different materials and processes according to actual needs to further improve the performance of the preparation. For example, the use of moisture-proof coating materials can further enhance the barrier ability to moisture on the basis of the hydrophobicity of the original sustained-release material, further reduce the risk of drug moisture absorption, and is particularly suitable for high-humidity storage environments; if enteric coating materials are used, the diclofenac sodium sustained-release tablets can remain stable in the acidic environment of the stomach, avoiding premature release of the drug to irritate the stomach, and the drug will not be released until it reaches the alkaline environment of the intestine, thereby improving the safety and effectiveness of the drug and reducing the occurrence of gastrointestinal adverse reactions.

[0015] Compared with the prior art, the technical effects of the present invention are:

[0016] (1) Significantly reduced hygroscopicity: Experimental data show that the moisture absorption rate of the diclofenac sodium sustained-release tablets of Examples 1 to 3 using ellagic acid-shellac-chitosan sustained-release material at 25° C. and 75% relative humidity for 48 hours is only significantly lower than that of Comparative Examples 1 to 5.

[0017] (2) Good stability: In the accelerated test, the content of diclofenac sodium in Examples 1 to 3 of the present invention decreased very little within 6 months, while the content of diclofenac sodium in Comparative Examples 1 to 5 decreased significantly. This indicates that the sustained-release system used in the present invention can not only isolate moisture but also resist the influence of other external factors on diclofenac sodium to a certain extent, reduce drug degradation or deterioration, and ensure the stability of the drug during long-term storage.

[0018] (3) Ideal sustained-release effect: The sustained-release material of the present invention can effectively control the drug release rate, allowing the drug to maintain an effective concentration in the body for a long time, reducing the frequency of medication, improving patient compliance, and avoiding adverse reactions caused by sudden drug release. Dissolution tests showed that the dissolution rates of Examples 1 to 3 increased slowly within 0.5 to 8 hours, reaching 96.04% to 97.77% at 16 hours, and nearly completely dissolved at 18 hours. In contrast, Comparative Examples 1 to 5 had a faster dissolution rate in the early stage, and some of the comparative examples had a dissolution rate exceeding 95% at 12 hours.

[0019] (4) Synergistic Innovation of Ingredients: The synergistic effect of ellagic acid, shellac, and chitosan is the key innovation of this invention. The combination of these three ingredients forms a unique sustained-release structure that is significantly superior to sustained-release materials made from a single ingredient or other combination of ingredients in terms of moisture absorption, stability, and sustained-release performance.

[0020] (5) Process feasibility and repeatability: The preparation method (wet granulation tableting method) adopted in the present invention is a mature pharmaceutical process with clear operating steps and stable process parameters. The equipment used is conventional equipment in the pharmaceutical industry. It has good industrial production feasibility and repeatability, which is conducive to large-scale production and promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 : Content changes of diclofenac sodium sustained-release tablets of Examples 1 to 3 and Comparative Examples 1 to 5.

[0022] Figure 2 : The sustained-release effects of the diclofenac sodium sustained-release tablets of Examples 1 to 3 and Comparative Examples 1 to 5. DETAILED DESCRIPTION

[0023] In order to make the purpose and technical solution of the present invention more clear, the present invention is further described below in conjunction with the embodiments, but the scope of protection of the present invention is not limited to these embodiments, and the embodiments are only used to illustrate the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the scope of protection of the present invention.

[0024] Ellagic acid-shellac-chitosan sustained-release material

[0025] (1) Solution preparation: Weigh 20 g of chitosan, dissolve it in 2% (v / v) acetic acid solution, stir at room temperature of 25°C until completely dissolved, prepare a chitosan solution with a mass concentration of 2%, and set aside; weigh 30 g of shellac, add an appropriate amount of ethanol solution (volume fraction 95%), heat and stir in a 60°C water bath until the shellac is completely dissolved, and prepare a shellac ethanol solution with a mass concentration of 5%; weigh 10 g of ellagic acid, add a small amount of dimethyl sulfoxide (DMSO), dissolve it by ultrasonication, and then slowly add it to the above chitosan solution and stir evenly.

[0026] (2) Film formation: Under stirring conditions, slowly add the shellac ethanol solution to the chitosan solution containing ellagic acid, and continue stirring for 30 minutes to fully mix the three components to form a mixed solution; pour the mixed solution into a mold, and evaporate the solvent naturally at room temperature. After the ethanol and DMSO have basically evaporated, transfer the mold to a constant temperature drying oven at 45°C and dry it for 24 hours to form a uniform film-like sustained-release material.

[0027] (3) Post-treatment: The dried sustained-release material was removed from the mold, and the surface was rinsed with deionized water to remove residual acetic acid and other impurities. The material was then placed in a vacuum drying oven and dried at 35°C to a constant weight to obtain the ellagic acid-shellac-chitosan sustained-release material.

[0028] Shellac-chitosan sustained-release material

[0029] (1) Solution preparation: Weigh 20 g of chitosan, dissolve it in 2% (v / v) acetic acid solution, and stir at room temperature of 25°C until completely dissolved to prepare a chitosan solution with a mass concentration of 2%, which is set aside; weigh 30 g of shellac, add an appropriate amount of ethanol solution (volume fraction 95%), heat and stir in a water bath at 60°C until the shellac is completely dissolved to prepare a shellac ethanol solution with a mass concentration of 5%.

[0030] (2) Film formation: Under stirring conditions, slowly add the shellac ethanol solution to the chitosan solution and continue stirring for 30 minutes to fully mix and form a mixed solution; pour the mixed solution into a mold and evaporate the solvent naturally at room temperature. After the ethanol and DMSO have basically evaporated, transfer the mold to a constant temperature drying oven at 45°C and dry it for 24 hours to form a uniform film-like sustained-release material.

[0031] (3) Post-treatment: The dried sustained-release material was removed from the mold, and the surface was rinsed with deionized water to remove residual acetic acid and other impurities. The material was then placed in a vacuum drying oven and dried at 35°C to a constant weight to obtain the shellac-chitosan sustained-release material.

[0032] Ellagic acid-peach gum-chitosan sustained-release material

[0033] (1) Solution preparation: Weigh 20 g of chitosan, dissolve it in 2% (v / v) acetic acid solution, stir at room temperature of 25°C until completely dissolved, prepare a chitosan solution with a mass concentration of 2%, and set aside; weigh 30 g of peach gum, add an appropriate amount of ethanol solution (volume fraction 95%), heat and stir in a 60°C water bath until the peach gum is completely dissolved, and prepare a peach gum ethanol solution with a mass concentration of 5%; weigh 10 g of ellagic acid, add a small amount of dimethyl sulfoxide (DMSO), dissolve it by ultrasonication, and then slowly add it to the above chitosan solution and stir evenly.

[0034] (2) Film formation: under stirring conditions, slowly add the peach gum ethanol solution to the chitosan solution containing ellagic acid, and continue stirring for 30 minutes to fully mix the three components to form a mixed solution; pour the mixed solution into a mold, and evaporate the solvent naturally at room temperature. After the ethanol and DMSO have basically evaporated, transfer the mold to a constant temperature drying oven at 45°C and dry it for 24 hours to form a uniform film-like sustained-release material.

[0035] (3) Post-treatment: The dried sustained-release material was removed from the mold, and the surface was rinsed with deionized water to remove residual acetic acid and other impurities. The material was then placed in a vacuum drying oven and dried at 35°C to a constant weight to obtain the ellagic acid-peach gum-chitosan sustained-release material.

[0036] Ellagic acid-shellac sustained-release material

[0037] (1) Solution preparation: Weigh 30 g of shellac, add an appropriate amount of ethanol solution (95% by volume), heat and stir in a 60°C water bath until the shellac is completely dissolved, and prepare a shellac ethanol solution with a mass concentration of 5%; weigh 10 g of ellagic acid, add a small amount of dimethyl sulfoxide (DMSO), dissolve it by ultrasonication, and stir evenly.

[0038] (2) Film formation: Under stirring conditions, slowly add the shellac ethanol solution to the ellagic acid solution, continue stirring for 30 minutes, mix thoroughly and evenly to form a mixed solution; pour the mixed solution into a mold, and evaporate the solvent naturally at room temperature. After the ethanol and DMSO have basically evaporated, transfer the mold to a constant temperature drying oven at 45°C and dry for 24 hours to form a uniform film-like sustained-release material.

[0039] (3) Post-treatment: The dried sustained-release material was removed from the mold, and the surface was rinsed with deionized water to remove residual acetic acid and other impurities. The material was then placed in a vacuum drying oven and dried at 35°C to a constant weight to obtain the ellagic acid-shellac sustained-release material.

[0040] Gallic acid-shellac-chitosan sustained-release material

[0041] (1) Solution preparation: Weigh 20 g of chitosan, dissolve it in 2% (v / v) acetic acid solution, stir at room temperature of 25°C until completely dissolved, prepare a chitosan solution with a mass concentration of 2%, and set aside; weigh 30 g of shellac, add an appropriate amount of ethanol solution (volume fraction 95%), heat and stir in a 60°C water bath until the shellac is completely dissolved, and prepare a shellac ethanol solution with a mass concentration of 5%; weigh 10 g of gallic acid, add a small amount of dimethyl sulfoxide (DMSO), dissolve it by ultrasonication, and then slowly add it to the above chitosan solution and stir evenly.

[0042] (2) Film formation: Under stirring conditions, slowly add the shellac ethanol solution to the chitosan solution containing gallic acid, and continue stirring for 30 minutes to fully mix the three components to form a mixed solution; pour the mixed solution into a mold, and evaporate the solvent naturally at room temperature. After the ethanol and DMSO have basically evaporated, transfer the mold to a constant temperature drying oven at 45°C and dry it for 24 hours to form a uniform film-like sustained-release material.

[0043] (3) Post-treatment: The dried sustained-release material was removed from the mold, and the surface was rinsed with deionized water to remove residual acetic acid and other impurities. The material was then placed in a vacuum drying oven and dried at 35°C to a constant weight to obtain a gallic acid-shellac-chitosan sustained-release material.

[0044] Example 1 Diclofenac sodium sustained-release tablets

[0045] formula:

[0046]

[0047] Preparation method:

[0048] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powder and filler;

[0049] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0050] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0051] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0052] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0053] (6) Tablet pressing.

[0054] Example 2 Diclofenac sodium sustained-release tablets

[0055] formula:

[0056]

[0057] Preparation method:

[0058] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powder and filler;

[0059] (2) Granulation: Prepare a solution of the binder at a concentration of 8%, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0060] (3) Drying: Place the wet granules in a drying device, control the temperature at 55±5°C, and dry until the moisture content of the granules reaches 1.5%.

[0061] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0062] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0063] (6) Tablet pressing.

[0064] Example 3 Diclofenac sodium sustained-release tablets

[0065] formula:

[0066]

[0067] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powder and filler;

[0068] (2) Granulation: Prepare a 2% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0069] (3) Drying: Place the wet granules in a drying device, control the temperature at 45±5°C, and dry until the moisture content of the granules reaches 2.5%.

[0070] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0071] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0072] (6) Tablet pressing.

[0073] Comparative Example 1 Diclofenac Sodium Sustained-Release Tablets

[0074] formula:

[0075]

[0076]

[0077] Preparation method:

[0078] (1) Mixing: uniformly mixing diclofenac sodium, shellac-chitosan sustained-release material powder and filler;

[0079] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0080] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0081] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0082] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0083] (6) Tablet pressing.

[0084] Comparative Example 2 Diclofenac Sodium Sustained-Release Tablets

[0085] formula:

[0086]

[0087] Preparation method:

[0088] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-peach gum-chitosan sustained-release material powder and filler;

[0089] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0090] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0091] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0092] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0093] (6) Tablet pressing.

[0094] Comparative Example 3: Diclofenac sodium sustained-release tablets

[0095] formula:

[0096]

[0097] Preparation method:

[0098] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-shellac sustained-release material powder and filler;

[0099] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0100] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0101] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0102] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0103] (6) Tablet pressing.

[0104] Comparative Example 4 Diclofenac Sodium Sustained-Release Tablets

[0105] formula:

[0106]

[0107]

[0108] Preparation method:

[0109] (1) Mixing: Evenly mix diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powder and filler;

[0110] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0111] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0112] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0113] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0114] (6) Tablet pressing.

[0115] Comparative Example 5: Diclofenac Sodium Sustained-Release Tablets

[0116] formula:

[0117]

[0118] Preparation method:

[0119] (1) Mixing: Evenly mix diclofenac sodium, gallic acid-shellac-chitosan sustained-release material powder and filler;

[0120] (2) Granulation: Prepare a 4.5% solution of the binder, add it to the above mixed powder to make a soft material, and pass it through a sieve to make wet granules.

[0121] (3) Drying: Place the wet granules in a drying device, control the temperature at 50±5°C, and dry until the moisture content of the granules is 2%.

[0122] (4) Granulation: The dried granules are sieved to make the granules uniform in size.

[0123] (5) Total mixing: Add the granulated particles and lubricant into the mixing equipment and mix them again to make the lubricant evenly coated on the surface of the particles.

[0124] (6) Tablet pressing.

[0125] Hygroscopicity of diclofenac sodium sustained-release tablets

[0126] Take an appropriate amount of diclofenac sodium sustained-release tablets, remove the packaging, and place them in a clean, dry weighing bottle. Accurately weigh and record the initial mass m1. Adjust the temperature and humidity chamber to 25°C and 75% relative humidity. Place the weighing bottle containing the sustained-release tablets in the chamber. Open the bottle cap to expose the sample to the set temperature and humidity. After 48 hours, remove the weighing bottle, quickly replace the cap, and weigh on an analytical balance. Record the mass m2. Moisture absorption (%) = (m2 - m1) / m1 × 100%.

[0127] Table 1 Hygroscopicity of diclofenac sodium sustained-release tablets

[0128] Moisture absorption rate (%) Example 1 0.32 Example 2 0.41 Example 3 0.37 Comparative Example 1 2.65 Comparative Example 2 2.14 Comparative Example 3 2.09 Comparative Example 4 1.26 Comparative Example 5 3.30

[0129] As shown in Table 1, the moisture absorption rates of the diclofenac sodium sustained-release tablets in Examples 1, 2, and 3 were significantly lower than those in the comparative examples. The ellagic acid-shellac-chitosan sustained-release materials used in Examples 1, 2, and 3, with their three components working together, form a structurally stable, hydrophobic sustained-release system. This system effectively prevents contact between water and diclofenac sodium, thereby reducing moisture absorption. In contrast, the sustained-release materials in the comparative examples, due to differences in composition and structure, disrupt the synergistic effects of the original components, resulting in changes in the material structure and increased hygroscopicity.

[0130] Stability of diclofenac sodium sustained-release tablets

[0131] The content of diclofenac sodium is determined according to the high performance liquid chromatography method (General Chapter 0512) in the "Chinese Pharmacopoeia". Test solution: Take 5 tablets of this product, place them in a 100ml volumetric flask, add an appropriate amount of 70% methanol, sonicate to dissolve the diclofenac sodium, let cool, dilute to the mark with 70% methanol, shake well, centrifuge, accurately measure an appropriate amount of supernatant, and quantitatively dilute with 70% methanol to make a solution containing approximately 0.25mg per 1ml. Reference solution: Take the diclofenac sodium reference substance, accurately weigh it, dissolve it in 70% methanol and quantitatively dilute it to make a solution containing approximately 0.25mg per 1ml. System suitability solution: Take an appropriate amount of diclofenac sodium, dissolve it in water to make a solution containing approximately 1mg per 1ml, and expose the solution to ultraviolet light (254nm) for 15 minutes. Chromatographic conditions: Use octadecylsilane bonded silica gel as the filler; methanol-4% glacial acetic acid solution (70:30) as the mobile phase; detection wavelength: 276 nm; injection volume for system suitability solution: 20 μl; injection volume for other solutions: 10 μl. System suitability requirement: In the system suitability solution chromatogram, the resolution between the diclofenac peak and the impurity peak at approximately 0.8 relative retention time should be greater than 4.0. Assay: Accelerate the amount of test solution and reference solution, inject them into the liquid chromatograph, and record the chromatogram. Calculate the peak area using the external standard method. (Accelerated test: 40°C ± 2°C, relative humidity 75 ± 5%, 6 months.)

[0132] Table 2 Diclofenac sodium content

[0133]

[0134] As shown in Table 2, under the conditions of the accelerated test, the diclofenac sodium content of Examples 1, 2, and 3 decreased by a small margin within 6 months and was maintained at a relatively high level, indicating that the diclofenac sodium sustained-release tablets prepared using the ellagic acid-shellac-chitosan sustained-release material have good stability. This indicates that the three components in the ellagic acid-shellac-chitosan sustained-release material cooperate with each other to form a structurally stable and hydrophobic sustained-release system. This system can not only effectively prevent moisture from contacting diclofenac sodium and reduce moisture absorption, but also isolate the impact of external factors on diclofenac sodium to a certain extent, reducing the possibility of its degradation or deterioration, thereby maintaining the diclofenac sodium content stable over a long period of time.

[0135] Dissolution of diclofenac sodium sustained-release tablets

[0136] The dissolution rate of diclofenac sodium sustained-release tablets was determined according to the dissolution and release rate determination method (General Chapter 0931, Method 1) in the Chinese Pharmacopoeia. Dissolution conditions: 900 ml of phosphate buffer (68.05 g of potassium dihydrogen phosphate, 56 ml of 1 mol / L sodium hydroxide solution, diluted to 10,000 ml with water, shaken well, pH 6.0 ± 0.05) was used as the dissolution medium. The rotation speed was 30 rpm. The procedure was repeated according to the instructions. After 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 16 h, 5 ml of the solution was collected and immediately replenished with the same volume of dissolution medium at the same temperature. Test solution: The solution collected at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 16 h was filtered and the filtrate was collected. Reference solution: Accurately weigh approximately 15 mg of diclofenac sodium reference substance into a 50 mL volumetric flask. Dissolve in 2 mL of methanol. Dilute to volume with dissolution medium and shake well. Chromatographic conditions and system suitability requirements: See the Assay section. Assay method: See the Assay section. Calculate the amount dissolved at different times.

[0137] Table 3 Dissolution of diclofenac sodium sustained-release tablets

[0138]

[0139] As shown in Table 3, compared with Comparative Examples 1 to 5, the diclofenac sodium sustained-release of Examples 1 to 3 has a better sustained-release effect. First, the dissolution rate of Examples 1 to 3 of the present invention is more gentle: within 0.5-8 hours, the solubility of Examples 1 to 3 increases relatively slowly and steadily, while the dissolution rate of the comparative example increases faster. This shows that the ellagic acid-shellac-chitosan sustained-release material in the examples can more effectively control the release rate of the drug, allowing the drug to be released continuously and stably over a longer period of time. Furthermore, the final dissolution time of Examples 1 to 3 of the present invention is longer: Examples 1 to 3 dissolve more slowly in the early stage and can maintain the sustained-release state of the drug for a longer period of time. For example, the solubility of Example 1 is 96.25% at 16 hours, while the solubility of Comparative Example 1 reaches 95.33% at 12 hours, indicating that the sustained-release material used in Examples 1 to 3 can maintain the effective concentration of the drug in the body for a longer time, thereby reducing the frequency of medication and improving patient compliance.

Claims

1. A diclofenac sodium sustained-release tablet, characterized in that: The diclofenac sodium sustained-release tablet comprises, by weight, 25 to 100 parts of diclofenac sodium, 10 to 40 parts of ellagic acid-shellac-chitosan sustained-release material, 58 to 260 parts of filler, 0.1 to 2 parts of lubricant, and 5 to 20 parts of adhesive.

2. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The mass ratio of ellagic acid, shellac and chitosan in the ellagic acid-shellac-chitosan sustained-release material is 1:3:

2.

3. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The preparation method of the ellagic acid-shellac-chitosan sustained-release material is as follows: (1) Solution preparation: Dissolve chitosan in acetic acid solution and stir to make a 2% chitosan solution; dissolve shellac in 95% ethanol solution and heat in a water bath and stir to make a 5% shellac ethanol solution; add a small amount of dimethyl sulfoxide to dissolve ellagic acid by ultrasonication, then pour into the chitosan solution and stir evenly; (2) Film formation: Add the shellac ethanol solution to the chitosan solution containing ellagic acid under stirring, stir to obtain a mixture, pour it into a mold, evaporate the solvent at room temperature, and then move it to a drying oven to dry and form a film; (3) Post-treatment: Take out the film, rinse it with deionized water, and dry it in a vacuum drying oven to constant weight.

4. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The filler is selected from at least one of starch, lactose, microcrystalline cellulose, mannitol, dextrin and sucrose.

5. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The binder is selected from at least one of hydroxypropyl methylcellulose, povidone, and sodium carboxymethylcellulose.

6. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The lubricant is selected from at least one of magnesium stearate, micropowder silica gel and talc.

7. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The diclofenac sodium sustained-release tablets can also be coated.

8. The diclofenac sodium sustained-release tablet according to claim 1, characterized in that The diclofenac sodium sustained-release tablets are prepared by a wet granulation tableting method.

9. The diclofenac sodium sustained-release tablet according to claim 8, characterized in that The wet granulation tableting method is: (1) Diclofenac sodium, ellagic acid-shellac-chitosan sustained-release material powders are mixed with fillers, a binder solution with a concentration of 2% to 8% is added, a soft material is prepared, sieved, dried, granulated, a lubricant is added, mixed, and tableted.

10. The diclofenac sodium sustained-release tablet according to claim 9, characterized in that The concentration of the binder solution was 4.5%.

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