Preparation method of escomeprazole magnesium sodium bicarbonate capsule

Abstract

The escomeprazole magnesium sodium bicarbonate capsule preparation provided by the invention is a stomach quick release preparation, sodium bicarbonate is added in a prescription as an alkaline auxiliary material, gastric acid can be effectively neutralized, escomeprazole magnesium is better protected, and the prepared capsule has a better dissolution effect and is easier to absorb by people.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a method for preparing esomeprazole magnesium sodium bicarbonate capsules. Background Art

[0002] Esomeprazole magnesium is a proton pump inhibitor, a drug that inhibits gastric acid secretion. It can be used for diseases with increased gastric acid, such as reflux esophagitis, chronic gastritis, peptic ulcer and other diseases. Esomeprazole magnesium can specifically act on the secretory microtubules and tubular alveoli in the cytoplasm formed by the apical membrane of gastric mucosal parietal cells, that is, the location of the gastric parietal cell proton pump (H+, K+-ATPase), and convert it into the active form of sulfenamide, inhibiting the activity of H+, K+-ATPase, blocking the last step of gastric acid secretion, so that H+ in the parietal cells cannot be transported to the gastric cavity, and the acid content in the gastric juice is greatly reduced. After taking the medicine, the pH in the stomach rises rapidly with the obvious decrease in gastric acid secretion. The relief rate of heartburn and pain is relatively fast. The cure rate of duodenal ulcer is also high, and the recurrence rate is low.

[0003] Most of the existing esomeprazole magnesium are sustained-release preparations, which are enteric-coated to protect the drug from gastric acid. However, the process of enteric coating is relatively complicated, and the coating also delays the onset of the drug, and has no initial inhibitory effect on gastric acid. Therefore, it is urgent to develop a new dosage form that can take effect quickly, does not require coating, but can prevent its absorption in the stomach, so that most of it is targeted for absorption in the duodenum. Summary of the invention

[0004] In order to improve the above technical problems, the present invention provides a method for preparing esomeprazole magnesium sodium bicarbonate capsules, wherein the components of the esomeprazole magnesium sodium bicarbonate capsules are composed, by mass, of 223 parts of esomeprazole magnesium, 11,000 parts of sodium bicarbonate, 170 parts of cross-linked sodium carboxymethyl cellulose and 60 parts of sodium stearyl fumarate;

[0005] The preparation method comprises the following steps:

[0006] (1) Sieving: Mix esomeprazole magnesium and one-quarter of the weight of sodium bicarbonate and sieve to obtain mixed powder 1;

[0007] (2) Premix-1: Mix the mixed powder 1 with one quarter of the weight of sodium bicarbonate to obtain mixed powder 2;

[0008] (3) Premix-2: One quarter by weight of sodium bicarbonate, cross-linked sodium carboxymethyl cellulose and another one quarter by weight of bicarbonate are sequentially added to mixed powder 2 to obtain mixed powder 3;

[0009] (4) Total mixing: adding sodium stearyl fumarate to mixed powder 3 and continuing to mix to obtain drug powder;

[0010] (5) Filling the drug powder into capsules to obtain the esomeprazole magnesium sodium bicarbonate capsules.

[0011] According to an embodiment of the present invention, the components of the esomeprazole magnesium sodium bicarbonate capsules are composed of 22.3 mg of esomeprazole magnesium, 1100.0 mg of sodium bicarbonate, 17.0 mg of cross-linked sodium carboxymethyl cellulose and 6.0 mg of sodium stearyl fumarate.

[0012] According to an embodiment of the present invention, the components of the esomeprazole magnesium sodium bicarbonate capsules are composed of 2.23 kg of esomeprazole magnesium, 110 kg of sodium bicarbonate, 1.7 kg of cross-linked sodium carboxymethyl cellulose and 0.6 kg of sodium stearyl fumarate.

[0013] According to an embodiment of the present invention, the mesh number of the sieving is 60 meshes.

[0014] According to an embodiment of the present invention, the sieving may further include the step of sieving sodium bicarbonate, cross-linked sodium carboxymethyl cellulose and sodium stearyl fumarate.

[0015] According to an embodiment of the present invention, the cumulative particle size distribution number of the esomeprazole magnesium is preferably D90≤11 μm.

[0016] According to an embodiment of the present invention, the sodium bicarbonate is oral sodium bicarbonate, and the cumulative particle size distribution number is preferably 150 μm<D90<210 μm.

[0017] According to an embodiment of the present invention, the mixing time is 5-30 min, for example 10 min, 15 min, 20 min, 25 min; the mixing time in step (2) can preferably be 10 min; the mixing time in step (3) can preferably be 25 min; the mixing time in step (4) can preferably be 10 min.

[0018] According to an embodiment of the present invention, the mixing speed is 5-20 rpm, such as 10 rpm.

[0019] According to an embodiment of the present invention, the capsule shell components of the capsule include gelatin, titanium dioxide, and food coloring.

[0020] Beneficial Effects

[0021] The capsule preparation provided by the present invention is a gastric rapid-release preparation. Compared with commercially available enteric-coated preparations, the product has a better dissolution effect and is more easily absorbed by humans. Sodium bicarbonate is added as an alkaline auxiliary material in the prescription, which can effectively neutralize gastric acid and better protect esomeprazole magnesium. However, since the amount of sodium bicarbonate used is relatively large, the present invention uses a step-by-step addition of a formula amount of sodium bicarbonate, and multi-step mixing allows the active ingredients to be mixed more evenly. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The production process flow chart of the capsule preparation of the present invention.

[0023] Figure 2 Dissolution curve of the capsule of the present invention. DETAILED DESCRIPTION

[0024] The technical solution of the present disclosure will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary illustrations and explanations of the present disclosure and should not be construed as limiting the scope of protection of the present disclosure. All technologies implemented based on the above content of the present disclosure are included in the scope of protection intended by the present disclosure.

[0025] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0026] Example 1

[0027] The formula of the esomeprazole magnesium sodium bicarbonate capsules of the present invention is as follows:

[0028] Esomeprazole magnesium sodium bicarbonate capsules

[0029] Components Dosage Esomeprazole magnesium 2.23kg Sodium bicarbonate 110kg Croscarmellose Sodium 1.7kg Sodium stearyl fumarate 0.6kg

[0030] The preparation process is carried out according to the following steps:

[0031] (1) Weighing ingredients

[0032] Weigh according to the table below (sodium bicarbonate (oral) is divided into four equal portions according to the prescribed amount).

[0033] Weighing quantity of raw materials and auxiliary materials and usage procedures

[0034]

[0035] Raw material usage conversion method:

[0036]

[0037] Note: Esomeprazole magnesium trihydrate (C 34 H 36MgN6O6S2·3H2O) has a molecular weight of 767.17, and esomeprazole magnesium (C 34 H 36 MgN6O6S2) molecular weight is 713.12

[0038]

[0039] Two batches of raw materials were used:

[0040]

[0041]

[0042] (2) Screening

[0043] Pour the weighed sodium bicarbonate (oral)-1 into the plastic bag containing the weighed esomeprazole magnesium raw material, mix manually for 1 minute, turn on the powder sifter, and then add the mixed powder in the bag to the powder sifter at a uniform speed to pass through a 60-mesh sieve, vibration frequency: 1500Hz, put the sieved material into a clean bag, weigh and record, mark it, and set it aside; then pass sodium bicarbonate (oral)-2, sodium bicarbonate (oral)-3, sodium bicarbonate (oral)-4, cross-linked sodium carboxymethyl cellulose, and sodium stearyl fumarate through a 60-mesh sieve respectively.

[0044] (3) Premix-1

[0045] Sodium bicarbonate (oral)-1 and esomeprazole magnesium raw material powders were mixed with sodium bicarbonate (oral)-2 in sequence, placed in a three-dimensional motion mixer, set the frequency to 25 Hz (equivalent to a tank speed of 10 rpm) and mixed for 10 minutes.

[0046] (4) Premix-2

[0047] After premixing-1 is completed, open the feed port and place sodium bicarbonate (oral)-3, cross-linked sodium carboxymethyl cellulose, and sodium bicarbonate (oral)-4 in the above-mentioned three-dimensional motion mixer in order, continue mixing, set the frequency to 25HZ (equivalent to a tank speed of 10 rpm) and mix for 25 minutes.

[0048] (5) Total mixing

[0049] After premixing-2, put the prescribed amount of sodium stearyl fumarate into the three-dimensional motion mixer and continue mixing. Set the frequency to 25HZ (equivalent to a tank speed of 10 rpm) and mix for 10 minutes. After mixing, open the feed valve and discharge the material into a double-layer plastic bag.

[0050] (6) Capsule filling

[0051] 1) Calculate the average filling amount (theoretical filling amount: 1.1453g / pill)

[0052]

[0053] 2) Calculation of filling range = average filling 1×(1±5.0%) ∩ average filling 2×(1±5.0%)

[0054] 3)

[0055] 4) Set the filling speed of the capsule filling machine to 10,000 to 33,000 capsules / hour, record the capsule filling amount every 15 minutes, 20 capsules each time, weigh each capsule filling amount, and the filling amount difference range is: average filling amount × (1 ± 5%).

[0056] 5) Use a capsule screening and polishing machine to polish the filled capsules. The capsules should have a bright surface, no drug powder attached, and be able to effectively remove empty capsule shells and half capsule shells.

[0057] 6) The polished capsules are packed in double-layer plastic bags.

[0058] (7) Bottle packaging

[0059] 1) BPL-200 automatic bottle unscrambler: put the high-density polyethylene bottles for medicinal use into the bottle storage bin, set the host frequency, boost frequency, etc., so that the equipment operation matches the subsequent production line equipment and can continuously and stably output bottles.

[0060] 2) BPS-D8S electronic tablet counter: adjust the width and height of the fence according to the outer diameter and height of the medicine bottle. When adjusting, pay attention to aligning the center of the bottle with the center of the feeding port. Adjust the gap between the feeding port and the bottle mouth. Set the parameters of the electronic tablet counter No. 1 and No. 2, and set the bottle quantity: 30 tablets / bottle. Check the bottle quantity every 10 minutes, and check 2 bottles continuously at each feeding port. The quantity of each bottle must be accurate. If inaccurate, stop the machine in time to find the cause.

[0061] 3) BPG-200 desiccant dispenser: adjust the height and width of the railing according to the diameter of the medicine bottle; adjust the position of the discharge port according to the height of the medicine bottle; the bagged strip desiccant is naturally wound on the reel, not too tightly, to ensure that the strip desiccant can naturally droop when the reel rotates slowly. The cutter works, cuts off a bag of desiccant, and the desiccant falls freely into the medicine bottle. After the desiccant is put in and stabilized, normal production can be carried out.

[0062] 4) BPX-200 rubbing capping machine: adjust various parts of the equipment according to the height of the medicine bottle and the diameter of the bottle cap, adjust the bottle screwing force, ensure that it is tightened without damaging the bottle cap and the runner, so that the bottle can pass smoothly and the capping effect is good. Normal production will resume after the capping is stable.

[0063] 5) BPF-200 aluminum foil sealing machine: adjust the gap between the bottom of the induction head and the upper plane of the medicinal high-density polyethylene bottle to about 2-5mm, so that it can pass smoothly, adjust the appropriate sealing conveying speed, close the induction working switch, put the medicinal high-density polyethylene bottle with the aluminum foil induction film installed (the aluminum foil side is opposite to the bottle mouth, and the paper pad side is opposite to the bottle cap), and the bottle cap is tightened on the conveyor belt for trial sealing. When the bottle comes out from the other end of the conveyor belt, unscrew the bottle cap and check the sealing quality. After meeting the sealing quality requirements, perform continuous automatic sealing. Check the sealing tightness every 10 minutes, and check 4 bottles continuously. The sealing is required to be tight and without muddy edges. If any abnormality is found, stop the machine in time to find the cause.

[0064] Preparation standards

[0065] The capsule prepared by the present invention contains esomeprazole magnesium and esomeprazole (C 17 H 19 N3O3S), it should be 90.0% to 110.0% of the labeled amount; sodium bicarbonate (NaHCO3) should be 95.0% to 105.0% of the labeled amount.

[0066]

prescription

[0067]

[0068]

Properties

[0069] [Identification] (1) Take an appropriate amount of the contents of this product, dissolve it in methanol and dilute it to make a solution containing approximately 25 mg of esomeprazole per 1 ml. Filter it and the filtrate will show the identification reaction of (2) (Chinese Pharmacopoeia 2020 Edition Part 4 General Rules 0301).

[0070] (2) Take an appropriate amount of the contents of this product, dissolve it in water and dilute it to make a solution containing about 25 mg per 1 ml, filter it, and the filtrate will show the identification reaction of bicarbonate (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0301).

[0071] (3) Tested according to the high performance liquid chromatography method (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0512).

[0072] Phosphate buffer (pH 11.0) contains 0.0137 mol of sodium phosphate and 0.0551 mol of disodium hydrogen phosphate per 1000 ml.

[0073] Test solution Take an appropriate amount of the product (equivalent to about 20 mg of esomeprazole) and place it in a 200 ml volumetric flask. Add about 120 ml of phosphate buffer (pH 11.0), shake, add 40 ml of ethanol, sonicate to dissolve the esomeprazole magnesium, cool, dilute to the scale with phosphate buffer (pH 11.0), shake well, filter, accurately measure 5 ml of the filtrate, place it in a 50 ml volumetric flask, dilute to the scale with water, and shake well.

[0074] Reference solution: Take about 20 mg of omeprazole reference substance, accurately weigh it, place it in a 100 ml volumetric flask, add 20 ml of ethanol to dissolve it, dilute it to the scale with phosphate buffer (pH 11.0), shake well, accurately measure 5 ml, place it in a 50 ml volumetric flask, dilute it to the scale with water, and shake well.

[0075] The chromatographic conditions were as follows: α1-acid glycoprotein bonded silica gel was used as the filler; acetonitrile-phosphate buffer (pH 6.0) (containing 0.0747 mol of disodium hydrogen phosphate and 0.400 mol of sodium dihydrogen phosphate per 1000 ml)-water (150:85:765) was used as the mobile phase; the detection wavelength was 302 nm; and the injection volume was 20 μl.

[0076] System suitability requires that in the chromatogram of the reference solution, the order of peaks is R-enantiomer and esomeprazole, the retention time of the esomeprazole peak is about 4 minutes, and the separation between the two peaks should meet the requirements.

[0077] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram.

[0078] The retention time of the main peak of the test solution should be consistent with the retention time of the esomeprazole peak in the reference solution.

[0079] [Inspection] Relevant substances are determined according to high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0512). New preparation for clinical use.

[0080] Test solution Take an appropriate amount of fine powder of the product (equivalent to 20 mg of esomeprazole) and place it in a 100 ml volumetric flask. Add mobile phase A to dissolve and dilute to the scale. Shake well, filter and take the filtrate.

[0081] For the control solution, accurately measure an appropriate amount of the test solution and quantitatively dilute it with mobile phase A to make a solution containing approximately 0.2 μg per 1 ml.

[0082] System suitability solution: Take appropriate amounts of omeprazole reference substance and impurity I reference substance, add mobile phase A to dissolve and dilute to make a mixed solution containing approximately 0.02 mg per 1 ml.

[0083] Sensitivity solution: Accurately measure an appropriate amount of the control solution and quantitatively dilute it with mobile phase A to make a solution containing approximately 0.1 μg per 1 ml.

[0084] Chromatographic conditions: Octadecylsilane bonded silica gel was used as filler; acetonitrile-phosphate buffer (pH 7.6) (containing 0.0052 mol of sodium dihydrogen phosphate and 0.032 mol of sodium dihydrogen phosphate per 1000 ml)-water (10:10:80) was used as mobile phase A, and acetonitrile-phosphate buffer (pH 7.6)-water (80:1:19) was used as mobile phase B, and linear gradient elution was performed according to the table below; the detection wavelength was 302 nm; the injection volume was 20 μl.

[0085]

[0086] System suitability requirements In the system suitability solution chromatogram, the retention time of the omeprazole peak is 14-19 minutes; the separation degree between the omeprazole peak and the impurity I peak (relative retention time is about 0.9) should be greater than 2.5. In the sensitivity solution chromatogram, the signal-to-noise ratio of the main component peak height should be greater than 10.

[0087] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram.

[0088] If there are impurity peaks in the limit test solution, the peak area of ​​impurity I shall not be greater than 2 times the main peak area of ​​the control solution (0.2%), the peak area of ​​impurity II (relative retention time is about 0.2) shall not be greater than 2 times the main peak area of ​​the control solution (0.2%), the area of ​​other single impurity peaks shall not be greater than 2 times the main peak area of ​​the control solution (0.2%), and the sum of the areas of all impurity peaks shall not be greater than 10 times the main peak area of ​​the control solution (1.0%)

[0089] Take the contents with different filling amounts, mix them, accurately weigh 0.5g of the contents, put them in a 250ml volumetric flask, accurately add 100ml of hydrochloric acid titration solution (0.1mol / L), seal it, shake it continuously at 37℃ for 1 hour, cool it, filter it, accurately measure 50ml of the filtrate, and titrate it with sodium hydroxide titration solution (0.1mol / L) to pH 3.5. For every 1g of the test sample, the consumption of hydrochloric acid titration solution (0.1mol / L) shall not be less than 100ml.

[0090] Content uniformity Take 1 capsule of this product, pour the contents into a 50ml measuring bottle, wash the capsule shell with 5ml of methanol, add 5ml of phosphate buffer (pH11.0) (containing 0.028mol of sodium phosphate and 0.11mol of disodium hydrogen phosphate per 1000ml), dissolve the esomeprazole magnesium by ultrasound, let cool, dilute to the scale with water, shake well, filter, accurately measure 1ml of the filtrate, put it in a 10ml measuring bottle, dilute to the scale with water, shake well, as the test solution; take about 20mg of omeprazole reference substance, accurately weigh, put it in a 50ml measuring bottle, add 5ml of methanol and 5ml of phosphate buffer (pH11.0), dissolve it by ultrasound, let cool, dilute to the scale with water, shake well, accurately measure 1ml, put it in a 10ml measuring bottle, dilute to the scale with water, shake well, as the reference substance solution. The content of esomeprazole shall be determined according to the method under the content determination of esomeprazole and shall comply with the regulations (General Rules 0941 of Part IV of the 2020 Edition of the Chinese Pharmacopoeia).

[0091] The dissolution rate was determined according to the dissolution and release rate determination method (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0931 Method 2). The test results are shown in Figure 2 .

[0092] The dissolution conditions were: 900 ml of phosphate buffer (pH 7.4) as the dissolution medium, a rotation speed of 50 revolutions per minute, and operation according to the law. Samples were taken after 30 minutes.

[0093] Take an appropriate amount of the dissolution solution of the test sample, filter it, accurately measure 5 ml of the filtrate, accurately add 1 ml of 0.1 mol / L sodium hydroxide solution, and shake well.

[0094] Reference solution: Take about 20 mg of omeprazole reference substance, weigh accurately, place in a 100 ml volumetric flask, add 20 ml of methanol and 60 ml of phosphate buffer (pH 11.0) (same as content uniformity), shake to dissolve, dilute to the scale with phosphate buffer (pH 7.4), shake well, accurately measure 2 ml, place in a 20 ml volumetric flask, dilute to the scale with phosphate buffer (pH 7.4), shake well; accurately measure 5 ml, accurately add 1 ml of 0.1 mol / L sodium hydroxide solution, shake well.

[0095] System suitability solutions, chromatographic conditions and system suitability requirements are given under the assay.

[0096] For the determination method, see the item "Assay of esomeprazole" and calculate the amount of esomeprazole dissolved in each tablet.

[0097] 80% of the limit labeled amount shall comply with regulations.

[0098] Loss on drying: Take 4.0 g of the content of this product and dry it in a silica gel desiccator for 4 hours. The weight loss shall not exceed 0.25% (Chinese Pharmacopoeia 2020 Edition Part 4 General Rules 0831).

[0099] Microbial limit Take 10g of this product, add pH7.0 sterile sodium chloride-peptone buffer to 100ml, place in a 45℃ water bath and shake to disperse evenly, as a 1:10 test solution. For the total number of aerobic bacteria, molds and yeasts, take 1ml of the 1:10 test solution and use the plate method to check according to the law (Chinese Pharmacopoeia 2020 Edition Part 4 General Rules 1105 Plate Method), the total number of aerobic bacteria in 1g of the test product shall not exceed 10 3 cfu, total number of molds and yeasts shall not exceed 10 2 For Escherichia coli, take 10 ml of the test solution at a ratio of 1:10 and check according to the law (General Rules 1106 of Part IV of the Chinese Pharmacopoeia 2020 Edition). It shall not be detected in 1 g of the test product.

[0100] Others should comply with the relevant provisions under capsules (General Rules 0103 of Part IV of the Chinese Pharmacopoeia 2020 Edition).

[0101] [Content Determination] Esomeprazole was determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0102] Take the contents under the item of difference in amount of test solution, mix them evenly, accurately weigh an appropriate amount (equivalent to 40 mg of esomeprazole), place it in a 200ml volumetric flask, add 10ml of methanol and 10ml of phosphate buffer (pH 11.0) (same as under the item of uniformity of content), dissolve it by ultrasonication, dilute it to the scale with water, shake well, and filter; accurately measure 5ml of the filtrate, place it in a 20ml volumetric flask, and dilute it to the scale with water.

[0103] Reference solution: Take 10 mg of omeprazole reference substance, weigh accurately, place in a 50 ml volumetric flask, add 2.5 ml of methanol and 2.5 ml of phosphate buffer (pH 11.0), dissolve by ultrasound, dilute to the scale with water, and shake well; accurately measure 5 ml, place in a 20 ml volumetric flask, and dilute to the scale with water.

[0104] System suitability solution Take appropriate amounts of omeprazole reference substance and impurity I reference substance, add phosphate buffer (pH 7.6) (containing 0.0052 mol of sodium dihydrogen phosphate and 0.032 mol of sodium dihydrogen phosphate per 1000 ml) to dissolve and dilute to make a mixed solution containing approximately 0.02 mg per 1 ml.

[0105] Chromatographic conditions: octadecylsilane bonded silica gel was used as filler; acetonitrile-phosphate buffer (pH 7.6) (containing 0.0052 mol of sodium dihydrogen phosphate and 0.032 mol of disodium hydrogen phosphate per 1000 ml) (25:75) was used as mobile phase; detection wavelength was 302 nm; injection volume was 20 μl.

[0106] System suitability requirements In the system suitability solution chromatogram, the separation degree between the omeprazole peak and the impurity I peak should be no less than 2.5.

[0107] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram; calculate the peak area according to the external standard method.

[0108] Take the contents under the item of sodium bicarbonate filling amount difference, mix them evenly, accurately weigh an appropriate amount (equivalent to about 2g of sodium bicarbonate), put it in a 100ml volumetric flask, add an appropriate amount of water, shake to dissolve the sodium bicarbonate, and dilute it to the scale with water, shake well, and filter; accurately measure 50ml of the filtrate, add an appropriate amount of methyl red-bromocresol green mixed indicator solution, and titrate with hydrochloric acid titrant (0.5mol / L) until the solution changes from green to purple-red, boil for 2 minutes, cool, and continue to titrate until the solution changes from green to dark purple. Each 1ml of hydrochloric acid titrant (0.5mol / L) is equivalent to 42.00mg of NaHCO3.

[0109] The above is an exemplary description of the implementation of the technical solution of the present disclosure. It should be understood that the protection scope of the present disclosure is not limited to the above-mentioned implementation. Any modification, equivalent substitution, improvement, etc. made by those skilled in the art within the spirit and principle of the present disclosure shall be included in the protection scope of the claims of this application.

Claims

1. A method for preparing an esomeprazole magnesium sodium bicarbonate capsule, wherein the components of the esomeprazole magnesium sodium bicarbonate capsule are composed, by mass, of 223 parts of esomeprazole magnesium, 11,000 parts of sodium bicarbonate, 170 parts of cross-linked sodium carboxymethyl cellulose and 60 parts of sodium stearyl fumarate; The preparation method comprises the following steps: (1) Sieving: Mix esomeprazole magnesium and one-quarter of the weight of sodium bicarbonate and sieve to obtain mixed powder 1; (2) Premix-1: Mix the mixed powder 1 with one quarter of the weight of sodium bicarbonate to obtain mixed powder 2; (3) Premix-2: One quarter by weight of sodium bicarbonate, cross-linked sodium carboxymethyl cellulose and another one quarter by weight of bicarbonate are sequentially added to mixed powder 2 to obtain mixed powder 3; (4) Total mixing: adding sodium stearyl fumarate to the mixed powder 3 and continuing to mix to obtain a drug powder; (5) Filling the drug powder into capsules to obtain the esomeprazole magnesium sodium bicarbonate capsules.

2. The method according to claim 1, characterized in that The components of the esomeprazole magnesium sodium bicarbonate capsule are composed of 22.3 mg of esomeprazole magnesium, 1100.0 mg of sodium bicarbonate, 17.0 mg of cross-linked sodium carboxymethyl cellulose and 6.0 mg of sodium stearyl fumarate.

3. The method according to claim 1, characterized in that The components of the esomeprazole magnesium sodium bicarbonate capsule are composed of 2.23 kg of esomeprazole magnesium, 110 kg of sodium bicarbonate, 1.7 kg of cross-linked sodium carboxymethyl cellulose and 0.6 kg of sodium stearyl fumarate.

4. The method according to any one of claims 1 to 3, characterized in that: The mesh number of the sieving is 60 meshes.

5. The method according to any one of claims 1 to 4, wherein the sieving further comprises the step of sieving sodium bicarbonate, cross-linked sodium carboxymethyl cellulose and sodium stearyl fumarate.

6. The method according to any one of claims 1 to 5, characterized in that: The cumulative particle size distribution number of the esomeprazole magnesium is preferably D90≤11 μm.

7. The method according to any one of claims 1 to 6, characterized in that: The sodium bicarbonate is oral sodium bicarbonate, and the cumulative particle size distribution number is preferably 150 μm<D90<210 μm.

8. The method according to any one of claims 1 to 7, characterized in that: The mixing time is 5-30 min; the mixing time in step (2) is preferably 10 min; the mixing time in step (3) is preferably 25 min; and the mixing time in step (4) is preferably 10 min.

9. The method according to any one of claims 1 to 8, characterized in that: The mixing speed is 5-20 rpm, for example 10 rpm.

10. The method according to any one of claims 1 to 9, characterized in that: The capsule shell components of the capsule include gelatin, titanium dioxide and food coloring.

Images