Sodium rabeprazole enteric-coated tablet and preparation method thereof

Abstract

The invention belongs to the technical field of proton pump inhibition medicine preparations, and relates to a rabeprazole sodium enteric-coated tablet and a preparation method thereof. The technical problems that an existing rabeprazole sodium enteric-coated tablet is insufficient in stability, lagged in dissolution and the like are solved. The enteric-coated tablet consists of a tablet core and an enteric-coated coating layer wrapped outside the tablet core, wherein the tablet core comprises auxiliary materials such as rabeprazole sodium, a filling agent, an adhesive, a stable dissolution promoter and the like; the enteric coating layer comprises an enteric coating material, a plasticizer, an anti-sticking agent and a solvent. Through the synergistic effect of the compound stabilizer and process control, the stability and dissolution performance of the enteric-coated tablet are synergistically improved, meanwhile, the production process is simplified, and the preparation method is suitable for industrial application.

Description

Technical Field

[0001] This invention belongs to the field of proton pump inhibitor drug formulation technology, specifically relating to a rabeprazole sodium enteric-coated tablet and its preparation method. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Rabeprazole sodium belongs to the benzimidazole class of proton pump inhibitors. Its mechanism of action is to specifically inhibit the activity of H⁺ / K⁺-ATPase (proton pump) in gastric parietal cells, blocking the final step of gastric acid secretion, thereby effectively and persistently reducing gastric acidity. This drug is widely used clinically to treat various gastric acid-related diseases, including active duodenal ulcers, benign active gastric ulcers, symptomatic erosive or ulcerative reflux esophagitis, and for maintenance therapy of cured reflux esophagitis. In addition, it can be used in combination with appropriate antibiotics to eradicate Helicobacter pylori to prevent recurrence of Helicobacter pylori-related peptic ulcers. It is also suitable for treating special types of hyperacidity diseases such as Zollinger-Ellison syndrome, demonstrating significant clinical application value.

[0004] However, rabeprazole sodium has significant drawbacks in its physicochemical properties. The benzimidazole ring in its molecular structure is highly sensitive to acid, light, heat, and moisture, especially in acidic environments where it readily undergoes degradation reactions, generating pharmacologically inactive degradation products (such as demethylated derivatives and oxidation products). Since oral formulations first pass through the stomach (where the pH is typically 1.0-3.0), if directly formulated as ordinary tablets, rabeprazole sodium would be rapidly destroyed by the acidic environment in the stomach, resulting in the drug losing its efficacy before reaching the absorption site (primarily the small intestine). Therefore, it must be formulated as an enteric-coated tablet. The enteric coating protects the tablet core from the acidic environment of the stomach, allowing it to reach the small intestine with a higher pH (typically above 5.5) before releasing the drug, ensuring effective absorption and the exertion of its pharmacological effect.

[0005] Chinese patent CN104337789A discloses an enteric-coated formulation of proton pump inhibitor rabeprazole sodium and its preparation method. Rabeprazole sodium is the main drug, and the formulation is prepared by a three-layer coating. The three coating layers, from the inside to the outside, are: an alkaline protective layer, an isolation layer, and an enteric coating layer. The alkaline protective layer includes a film-forming agent, a lubricant, a light-blocking agent, an alkaline stabilizer, and a solvent. The pH value of the coating solution is 8.0 to 13.0.

[0006] Chinese patent CN107375226A discloses a rabeprazole sodium enteric-coated tablet and its preparation method, comprising a tablet core, an isolation layer, and an intestinal coating layer. The tablet core contains rabeprazole sodium, aluminum hydroxide, polyvinylpyrrolidone, a diluent, and a lubricant, and has good stability.

[0007] Although the aforementioned existing technologies have proposed improvements to address the stability issues of rabeprazole sodium and have improved the quality of enteric-coated formulations to some extent, there are still many technical limitations that need to be addressed, such as stability issues. Summary of the Invention

[0008] To address the instability of existing rabeprazole sodium enteric-coated tablets due to the drug's sensitivity to acid, light, and heat, as well as the technical problems of delayed dissolution and complex processes in some formulations, this invention provides a rabeprazole sodium enteric-coated tablet and its preparation method. By optimizing the formulation components and preparation process, the stability and dissolution performance are synergistically improved, while the production process is simplified, making it suitable for industrial applications.

[0009] The first objective of this invention is to provide a formulation for rabeprazole sodium enteric-coated tablets. The rabeprazole sodium enteric-coated tablets of this invention consist of a tablet core and an enteric coating layer surrounding the tablet core. The components are precisely proportioned by weight, as follows:

[0010] (1) Core components and proportions

[0011] The tablet core contains rabeprazole sodium as the main drug, with added fillers, binders, disintegrants, lubricants, composite stabilizers, and pH adjusters. The weight range of each component is as follows: Main drug: 10 parts rabeprazole sodium; Filler: 50-100 parts, selected from at least one of starch, lactose, microcrystalline cellulose, dextrin, mannitol, and sucrose, preferably a mixture of lactose, microcrystalline cellulose, and mannitol; Binder: 1-6 parts, selected from at least one of povidone, hydroxypropyl methylcellulose, and starch paste; Disintegrant: 3 parts rabeprazole sodium; -10 parts, selected from at least one of croscarmellose sodium, croscarmellose, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch; Lubricant: 0.5-2 parts, selected from one or more of magnesium stearate, talc, and micronized silica gel; pH adjuster: 1-4 parts, selected from at least one of sodium bicarbonate, sodium citrate, and disodium hydrogen phosphate; Composite stabilizer: 0.6-3 parts, a mixture of tert-butyl-p-hydroxyanisole (BHA), sodium glycocholate, and erythritol in a mass ratio of 1:3:2.

[0012] (2) Components and proportions of enteric coating layer

[0013] The enteric coating layer is used to isolate the acidic environment in the stomach, ensuring that the drug is released after the tablet core reaches the small intestine. The weight range of each component is as follows:

[0014] Enteric coating material: 5-12 parts, a mixture of acrylic resin IV and HPMCP55S (hydroxypropyl methylcellulose phthalate), in a mass ratio of 1:1 to 3:1; Plasticizer: 0.8-3 parts, selected from at least one of triacetin, glycerol, and diethyl phthalate; Anti-adhesive: 1-4 parts, selected from at least one of micronized silica gel, magnesium stearate, and glyceryl monostearate; Solvent: 70-150 parts, an ethanol-water mixture.

[0015] The first objective of this invention is to provide a method for preparing the above-mentioned rabeprazole sodium enteric-coated tablets, specifically including the following steps:

[0016] (1) Pretreatment of composite stabilizer

[0017] tert-butyl-p-hydroxyanisole, sodium glycocholate, and erythritol were added to a pulverizer at a mass ratio of 1:3:2 and pulverized at 3000-3500 r / min for 5-8 min, then passed through an 80-100 mesh sieve. Subsequently, using the "equal incremental method", the three pulverized components were placed in a three-dimensional mixer and mixed at 15-20 r / min for 25-35 min to obtain a uniform stabilizer premix.

[0018] (2) Core preparation

[0019] Pretreatment: Rabeprazole sodium is pulverized at 2800-3200 rpm for 6-8 minutes (passing through an 80-mesh sieve). The filler, disintegrant, and pH adjuster are also passed through an 80-mesh sieve. Mixing: The active ingredient, filler, disintegrant, and pH adjuster are first placed in a mixer and mixed at 15 rpm for 10 minutes. Then, the stabilizer premix is ​​added, and mixing continues at 18 rpm for 20-25 minutes. Softening: A 10%-15% binder concentration is added to the mixture, and it is stirred at 60 rpm until it "forms a clump when squeezed by hand but crumbles easily when pressed." Granulation and Drying: Granulation is performed using a 16-20 mesh sieve, and drying is carried out at 40-45℃ until the moisture content of the material is 2%-3%. Granulation and Blending: Granulation is performed using an 18-24 mesh sieve, and after adding lubricant, mixing is carried out at 12 rpm for 8-10 minutes. Tableting: The tableting machine pressure is adjusted to control the tablet hardness at 3-5 kg, with a tablet weight difference within ±5%.

[0020] (3) Preparation of enteric coating layer

[0021] Coating solution preparation: Add enteric coating material (acrylic resin IV and HPMCP55S) to an ethanol-water mixture (7:3) and stir at a stirring rate of 30-40 r / min for 30-40 min until completely dissolved; then add plasticizer (stir for 20 min) and anti-sticking agent in sequence; Coating: Place the tablet core in the coating pan, adjust the coating pan speed to 20-25 r / min, the inlet air temperature to 42-45℃, and the spray pressure to 0.2-0.3 MPa for coating; after the tablet weight gain is 3%-5%, continue drying for 15-20 min, cool to room temperature, and obtain rabeprazole sodium enteric-coated tablets.

[0022] Compared with the prior art, the technical advantages of the present invention are as follows:

[0023] (1) Synergistic innovation of composite stabilizers: This invention breaks through the limitations of existing technologies that use only one or two stabilizers. It adopts a composite system of "tert-butyl-p-hydroxyanisole-sodium glycine-erythritol" and achieves the dual functions of "anti-degradation + dissolution promotion" through a precise ratio of 1:3:2, thus solving the problem of traditional stabilizers that "only stabilize but do not dissolve".

[0024] (2) Precise control of process parameters: The process of "equal incremental mixing" for stabilizer pretreatment avoids the degradation of the main drug from the source and ensures the uniformity of the formulation quality.

[0025] (3) Significantly improved performance: Accelerated tests show that the content of the enteric-coated tablets of the present invention remains above 99.5%; light irradiation tests show that the content remains above 99.5%; dissolution tests show that the dissolution amount is ≥98.5% after 30 minutes, and the stability and dissolution performance are superior to the existing technology;

[0026] (4) Simplified process and safety: The technology of this invention does not require multiple coating layers such as "isolation layer" and "alkaline protective layer" in the prior art. It can achieve the requirements of stability and drug release by only "tablet core + enteric coating layer", which simplifies the process and reduces costs. The solvent adopts an ethanol-water mixed system to avoid the flammability and explosion risks of pure organic solvents and improve production safety. Attached Figure Description

[0027] Figure 1 Accelerated test of rabeprazole sodium enteric-coated tablet content.

[0028] Figure 2 Light exposure test: Rabeprazole sodium enteric-coated tablet content.

[0029] Figure 3 Dissolution rate of rabeprazole sodium enteric-coated tablets. Detailed Implementation

[0030] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0031] Example 1: Rabeprazole Sodium Enteric-coated Tablets

[0032] formula:

[0033] Preparation method:

[0034] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and erythritol were pulverized at 3200 r / min for 6 min and passed through a 90 mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (18 r / min) for 30 min by the "equal increment method" to obtain the stabilizer premix.

[0035] (2) Core preparation

[0036] Pretreatment: Rabeprazole sodium is pulverized at 3000 rpm for 7 min (passing through an 80-mesh sieve). Fillers, disintegrants, and pH adjusters are all passed through an 80-mesh sieve. Mixing: The main and auxiliary materials are mixed for 10 min (15 rpm), and the stabilizer premix is ​​added and mixed for another 22 min (18 rpm). Softening: 12% binder is added (stirring at 60 rpm) until the mixture "can be formed into a ball by hand and crumbles easily when pressed". Granulation and drying: Granulate at 18 mesh and dry at 40-45℃ to a moisture content of 2%-3%. Granulation and mixing: Granulate at 20 mesh and mix with lubricant for 9 min (12 rpm). Tableting: Hardness 3-5 kg, tablet weight difference within ±5%.

[0037] (3) Preparation of enteric coating layer

[0038] Coating solution: Add enteric material to solvent and stir for 35 min, then add plasticizer (mix for 20 min) and anti-sticking agent (disperse ultrasonically and pass through a 100-mesh sieve); Coating: Coating pan 22 r / min, air inlet 42-45℃, spray pressure 0.2-0.3 MPa, after gaining 4% weight, dry for 15-20 min, and cool to room temperature.

[0039] Example 2: Rabeprazole Sodium Enteric-coated Tablets

[0040] formula:

[0041] Preparation method:

[0042] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and erythritol were pulverized at 3000 r / min for 5 min and passed through an 80-mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (15 r / min) for 25 min using the "equal increment method" to obtain the stabilizer premix.

[0043] (2) Core preparation

[0044] Pretreatment: Rabeprazole sodium is pulverized at 2800 rpm for 6 min (passing through an 80-mesh sieve). Fillers, disintegrants, and pH adjusters are all passed through an 80-mesh sieve. Mixing: The main and auxiliary materials are mixed for 10 min (15 rpm), and the stabilizer premix is ​​added and mixed for another 20 min (18 rpm). Softening: 10% binder is added (stirring at 60 rpm) until the mixture "can be formed into a ball by hand and crumbles easily when pressed". Granulation and drying: Granulate at 16 mesh and dry at 40-45℃ to a moisture content of 2%-3%. Granulation and mixing: Granulate at 18 mesh and mix with lubricant for 8 min (12 rpm). Tableting: Hardness 3-5 kg, tablet weight difference within ±5%.

[0045] (3) Preparation of enteric coating layer

[0046] Coating solution: Add enteric material to solvent and stir for 30 min, then add plasticizer (mix for 20 min) and anti-sticking agent (disperse ultrasonically and pass through a 100-mesh sieve); Coating: Coating pan at 20 r / min, air inlet at 42-45℃, spray pressure at 0.2-0.3 MPa, after gaining 3% weight, dry for 15-20 min, and cool to room temperature.

[0047] Example 3: Rabeprazole Sodium Enteric-coated Tablets

[0048] formula:

[0049] Preparation method:

[0050] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and erythritol were pulverized at 3500 r / min for 8 min and passed through a 100-mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (20 r / min) for 35 min by the "equal increment method" to obtain the stabilizer premix.

[0051] (2) Core preparation

[0052] Pretreatment: Rabeprazole sodium is pulverized at 3200 rpm for 8 min (passing through an 80-mesh sieve). Fillers, disintegrants, and pH adjusters are all passed through an 80-mesh sieve. Mixing: The main and auxiliary materials are mixed for 10 min (15 rpm), and the stabilizer premix is ​​added and mixed for another 25 min (18 rpm). Softening: 15% binder is added (stirring at 60 rpm) until the mixture "can be formed into a ball by hand and crumbles easily when pressed". Granulation and drying: Granulate at 20 mesh and dry at 40-45℃ until the moisture content is 2%-3%. Granulation and mixing: Granulate at 24 mesh and mix with lubricant for 10 min (12 rpm). Tableting: Hardness 3-5 kg, tablet weight difference within ±5%.

[0053] (3) Preparation of enteric coating layer

[0054] Coating solution: Add enteric material to solvent and stir for 40 min, then add plasticizer (mix for 20 min) and anti-sticking agent (disperse ultrasonically and pass through a 100-mesh sieve); Coating: Coating pan at 25 r / min, air inlet at 42-45℃, spray pressure at 0.2-0.3 MPa, after gaining 5% weight, dry for 15-20 min, and cool to room temperature.

[0055] Comparative Example 1: Rabeprazole Sodium Enteric-coated Tablets

[0056] formula:

[0057] Preparation method:

[0058] (1) Stabilizer pretreatment: Sodium glycinecholate and erythritol were pulverized at 3200r / min for 6min and passed through a 90-mesh sieve. According to the prescription ratio, they were mixed in a three-dimensional mixer (18r / min) for 30min using the "equal increment method" to obtain the stabilizer premix.

[0059] Steps (2) and (3) are the same as in Example 1.

[0060] Comparative Example 2: Rabeprazole Sodium Enteric-coated Tablets

[0061] formula:

[0062] Preparation method:

[0063] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole and erythritol were pulverized at 3200 r / min for 6 min and passed through a 90-mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (18 r / min) for 30 min using the "equal increment method" to obtain the stabilizer premix.

[0064] Steps (2) and (3) are the same as in Example 1.

[0065] Comparative Example 3: Rabeprazole Sodium Enteric-coated Tablets

[0066] formula:

[0067] Preparation method:

[0068] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole and sodium glycocholate were pulverized at 3200 r / min for 6 min and passed through a 90-mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (18 r / min) for 30 min using the "equal increment method" to obtain the stabilizer premix.

[0069] Steps (2) and (3) are the same as in Example 1.

[0070] Comparative Example 4: Rabeprazole Sodium Enteric-coated Tablets

[0071] formula:

[0072] Preparation method:

[0073] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and erythritol were pulverized at 3200 r / min for 6 min and passed through a 90 mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (18 r / min) for 30 min by the "equal increment method" to obtain the stabilizer premix.

[0074] Steps (2) and (3) are the same as in Example 1.

[0075] Comparative Example 5: Rabeprazole Sodium Enteric-coated Tablets

[0076] formula:

[0077] Preparation method:

[0078] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and sorbitol were pulverized at 3200 r / min for 6 min and passed through a 90 mesh sieve; according to the prescription ratio, they were mixed in a three-dimensional mixer (18 r / min) for 30 min by the "equal increment method" to obtain the stabilizer premix.

[0079] Steps (2) and (3) are the same as in Example 1.

[0080] Comparative Example 6: Rabeprazole Sodium Enteric-coated Tablets

[0081] The formula is the same as in Example 1.

[0082] Preparation method:

[0083] (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycinecholate and erythritol were pulverized at 3200 r / min for 6 min and passed through a 90 mesh sieve; they were mixed in a three-dimensional mixer (18 r / min) for 30 min to obtain stabilizer premix.

[0084] Steps (2) and (3) are the same as in Example 1.

[0085] Comparative Example 7: Rabeprazole Sodium Enteric-coated Tablets

[0086] The formula is the same as in Example 1.

[0087] Preparation method:

[0088] (1) Core preparation

[0089] Pretreatment: Rabeprazole sodium is pulverized at 3000 rpm for 7 min (passing through an 80-mesh sieve). Fillers, disintegrants, and pH adjusters are all passed through an 80-mesh sieve. Mixing: The main and auxiliary materials are mixed for 10 min (15 rpm), then tert-butyl-p-hydroxyanisole, sodium glycinecholate, and erythritol are added, and the mixture is continued for 22 min (18 rpm). Softening: 12% binder is added (stirring at 60 rpm) until the mixture "can be formed into a ball by hand and crumbles easily when pressed". Granulation and drying: Granulation is done through an 18-mesh sieve and dried at 40-45℃ until the moisture content is 2%-3%. Granulation and mixing: Granulation is done through a 20-mesh sieve, and lubricant is added and mixed for 9 min (12 rpm). Tableting: The hardness is 3-5 kg, and the tablet weight difference is within ±5%.

[0090] (2) Preparation of enteric coating layer

[0091] Coating solution: Add enteric material to solvent and stir for 35 min, then add plasticizer (mix for 20 min) and anti-sticking agent (disperse ultrasonically and pass through a 100-mesh sieve); Coating: Coating pan 22 r / min, air inlet 42-45℃, spray pressure 0.2-0.3 MPa, after gaining 4% weight, dry for 15-20 min, and cool to room temperature.

[0092] Commercially available rabeprazole sodium enteric-coated tablets: National Drug Approval Number H20020330

[0093] Stability verification of rabeprazole sodium enteric-coated tablets

[0094] The content of rabeprazole sodium was determined according to the high performance liquid chromatography method (General Chapter 0512) of the Chinese Pharmacopoeia. Test solution: Accurately weigh an appropriate amount of the sample, dissolve it in solvent, and quantitatively dilute it to prepare a solution containing approximately 0.05 mg per ml. Reference solution: Accurately weigh an appropriate amount of rabeprazole sodium reference standard, dissolve it in solvent, and quantitatively dilute it to prepare a solution containing approximately 0.05 mg per ml. Solvents, system suitability solutions (1), system suitability solutions (2), chromatographic conditions and system suitability requirements, except for sensitivity requirements, are detailed under the section on related substances. Determination method: Accurately measure the test solution and reference solution, inject them separately into the liquid chromatograph, and record the chromatograms. Calculate the content by peak area using the external standard method.

[0095] 1. Accelerated testing

[0096] Accelerated test conditions: 40℃±2℃, relative humidity 75±5%, 6 months.

[0097] Table 1. Accelerated test results for rabeprazole sodium enteric-coated tablet content

[0098] Table 1 shows that the accelerated testing results of Examples 1-3 are significantly more stable than those of the comparative examples and the commercially available formulations. Due to defects in the stabilization system, the content of the comparative examples decreased significantly: Comparative example 1 lacking tert-butyl-p-hydroxyanisole (decreased by 3.7%), comparative example 2 lacking sodium glycocholate (decreased by 5.42%), and comparative example 3 lacking erythritol (decreased by 6.03%). The content of the commercially available formulations decreased by 3.61%, indicating that there is still room for optimization in the stabilization system of existing commercially available products.

[0099] 2. Light test

[0100] Light exposure test conditions: 30°C±2°C, relative humidity 60%±5%, light intensity 4500lx±500xl, 12 months.

[0101] Table 2. Rabeprazole Sodium Enteric-coated Tablet Content in Light Irradiation Test

[0102] Table 2 shows that the light exposure test results of Examples 1-3 are outstanding in terms of light resistance: the content remains above 99.50% after 12 months. The comparative examples, due to the lack of stabilizing components or improper processes, suffered severe light degradation, all of which showed the pattern of "incomplete stabilizing system leading to a sharp drop in light resistance". The light resistance of commercially available formulations is also relatively weak, further verifying the innovation of the stabilizing system of this invention.

[0103] Dissolution verification of rabeprazole sodium enteric-coated tablets

[0104] The dissolution rate of rabeprazole sodium enteric-coated tablets was determined according to the Chinese Pharmacopoeia. Acid-based dissolution: Simulating a gastric environment, the dissolution conditions were as follows: 700 ml of 0.1 mol / L hydrochloric acid solution was used as the dissolution medium, and the rotation speed was 100 rpm. The procedure was followed, and in Examples 1-3, the dissolution rate of rabeprazole sodium enteric-coated tablets was ≤2% within 120 minutes. Buffer solution dissolution: Dissolution conditions: After 120 minutes of acid-based dissolution, 300 ml of 0.6 mol / L tris(hydroxymethyl)aminomethane solution at 37°C was immediately added to the dissolution vessel. The pH was adjusted to 8.0 with 2 mol / L hydrochloric acid solution or 2 mol / L sodium hydroxide solution, and the rotation speed was 100 rpm. The procedure was followed, and samples were taken after 30 minutes. Test solution: The dissolution solution was filtered, and 3 ml of the filtrate was accurately measured. Immediately, 1 ml of 0.5 mol / L sodium hydroxide solution was accurately added, and the solution was shaken well. Reference solution: Accurately weigh 50 mg of rabeprazole sodium reference standard, place it in a 50 ml volumetric flask, add an appropriate amount of 0.5 mol / L sodium hydroxide solution to dissolve it, dilute to the mark with 0.5 mol / L sodium hydroxide solution, shake well, accurately measure 3 ml, place it in a 100 ml (10 mg specification) or 50 ml (20 mg specification) volumetric flask, dilute to the mark with 0.5 mol / L sodium hydroxide solution, shake well, accurately measure 1 ml, accurately add 3 ml of tris(hydroxymethyl)aminomethane buffer (add 300 ml of 0.6 mol / L tris(hydroxymethyl)aminomethane solution to 700 ml of 0.1 mol / L hydrochloric acid solution, adjust the pH to 8.0 with 2 mol / L hydrochloric acid solution or 2 mol / L sodium hydroxide solution), shake well. System suitability solution (1), system suitability solution (2), chromatographic conditions and system suitability requirements are shown under the content determination section. Assay: Inject the test solution and reference solution into the liquid chromatograph separately, and record the chromatogram. The dissolution amount per tablet is calculated based on peak area using the external standard method.

[0105] Table 3 Dissolution of Rabeprazole Sodium Enteric-coated Tablets

[0106] Dissolution rate is directly related to drug bioavailability. Table 3 shows that Examples 1-3 have fast dissolution rate and high completeness, which meets the requirements of "rapid release + complete drug release". The dissolution performance of the comparative examples is significantly insufficient. In contrast, the commercially available formulations have lag dissolution, indicating that the stable system of the present invention also has "dissolution promotion function", which solves the problem of "stable but not soluble" in traditional stable systems.

Claims

1. A rabeprazole sodium enteric-coated tablet, characterized in that, The rabeprazole sodium enteric-coated tablets consist of a tablet core and an enteric coating layer surrounding the tablet core. The components of each part are calculated by weight as follows: The tablet core comprises: 10 parts rabeprazole sodium, 50-100 parts filler, 1-6 parts binder, 3-10 parts disintegrant, 0.5-2 parts lubricant, 0.6-3 parts stabilizer, and 1-4 parts pH adjuster; the enteric coating layer comprises: 5-12 parts enteric coating material, 0.8-3 parts plasticizer, 1-4 parts anti-adhesion agent, and 70-150 parts solvent; The stabilizer is a mixture of tert-butyl-p-hydroxyanisole, sodium glycocholate, and erythritol.

2. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The filler is selected from at least one of starch, lactose, microcrystalline cellulose, dextrin, mannitol, and sucrose. Preferably, the filler is a mixture of lactose, microcrystalline cellulose, and mannitol.

3. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The adhesive is selected from at least one of polyvinylpyrrolidone, hydroxypropyl methylcellulose, and starch paste.

4. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The disintegrant is selected from at least one of croscarmellose sodium, croscarmellose, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch.

5. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The lubricant is selected from one or more of magnesium stearate, talc, and micronized silica gel; the pH adjuster is selected from at least one of sodium bicarbonate, sodium citrate, and disodium hydrogen phosphate.

6. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The stabilizer is a mixture of tert-butyl-p-hydroxyanisole, sodium glycocholate, and erythritol in a mass ratio of 1:3:

2.

7. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The enteric coating material is a mixture of acrylic resin IV and HPMCP 55S in a mass ratio of 1:1 to 3:

1.

8. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The plasticizer is selected from at least one of triacetin, glycerol, and diethyl phthalate; the anti-adhesion agent is selected from at least one of micronized silica gel, magnesium stearate, and glyceryl monostearate; and the solvent is an ethanol-water mixture.

9. The rabeprazole sodium enteric-coated tablets according to claim 1, characterized in that, The stabilizers are mixed using an equal-incremental mixing method.

10. A method for preparing the rabeprazole sodium enteric-coated tablets of claim 1, characterized in that, The method includes the following steps: (1) Stabilizer pretreatment: tert-butyl-p-hydroxyanisole, sodium glycocholate and erythritol were pulverized and sieved respectively; then mixed to obtain stabilizer premix; (2) Tablet core preparation: Rabeprazole sodium is pulverized and sieved, filler, disintegrant and pH adjuster are sieved; mixed, stabilizer premix is ​​added and mixed again; 10%-15% binder is added and stirred, granulated, dried, granulated, lubricant is added and mixed, and tableted; (3) Preparation of enteric coating layer: Add enteric material to solvent and stir, then add plasticizer and anti-sticking agent in sequence, coat and dry, and cool to room temperature.

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