CN110946845A - Dextrobeprazole sodium sustained-release capsule and preparation method thereof - Google Patents
Dextrobeprazole sodium sustained-release capsule and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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Abstract
The invention belongs to the technical field of pharmaceutical preparations and aims to improve the bioavailability of dextro-rabeprazole sodium in vivo. The product is hardly released in gastric acid and can be disintegrated in intestine to dissolve active ingredients, thereby avoiding the damage of the rabeprazole sodium in gastric acid. The product belongs to a double controlled release (DDR) containing 2 different types of enteric-coated pellets, thereby achieving 2 times of drug release. In the process of preparing the Eudragit S100 aqueous dispersion, different amounts of alkaline substances are added to neutralize carboxyl groups with different molar numbers in a polymer, so that the enteric material is controlled to be dissolved at different pH values, and thus, the two-time release is realized; and the coating is carried out by adopting the aqueous dispersion, so that ethanol residue is effectively avoided.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a dextro-rabeprazole sodium sustained-release capsule and a preparation method thereof.
Background
The dextro-rabeprazole sodium is a dextro-optical isomer of rabeprazole.
Chemical name: r- (+) -sodium 2- [ [ [4- (3-methoxypropoxy) -3-methyl-2-pyridinyl ] methyl ] sulfinyl ] -1H-benzimidazole; the dextro-rabeprazole is an R-type optical isomer of rabeprazole sodium (racemate), belongs to a proton pump inhibitor, and has a pharmacological action of blocking gastric acid secretion by forming covalent binding with two sites of a (H +, K +) -ATP enzyme system on the surface of a gastric parietal cell secretory tubule. This effect is dose-dependent and has an inhibitory effect on gastric acid secretion stimulated by both the basal and any stimulant. Binding to (H +, K +) -ATPase maintained the antisecretory effect over a period of 24 hours. Dextro-rabeprazole sodium, like rabeprazole sodium, is a prodrug that is protonated on parietal cells to convert to the active sulfenamide.
The structure of the dextro-rabeprazole sodium belongs to the azole PPIs antiulcer drug, the dextro-rabeprazole sodium contains sulfinyl benzimidazole, the stability is easily influenced by various factors such as light, heavy metal ions, temperature and the like, and particularly, the sulfinyl group of the dextro-rabeprazole sodium is subjected to destructive change under an acidic condition to generate discoloration and polymerization phenomena. Therefore, the gastric juice can degrade and destroy the rabeprazole sodium, so that the bioavailability and the curative effect of the medicament are reduced.
At present, most of preparation technologies for avoiding the release of active ingredients in gastric acid adopt a method of coating an enteric coating layer on an outer layer, and because the enteric coating material is generally an acidic high polymer material, the stability of the D-rabeprazole sodium is adversely affected by the weak acidity of the enteric coating material. Therefore, an isolating coat is required to be coated between the enteric-coated layer and the active ingredient, so that the contact between the enteric-coated material and the dextro-rabeprazole sodium is avoided, and the stability of the preparation is improved.
Disclosure of Invention
The invention provides a dextro-rabeprazole sodium sustained-release capsule and a preparation method thereof.
In order to solve the problem of poor stability of the rabeprazole sodium under an acidic condition and improve the bioavailability, the invention aims to provide the rabeprazole sodium sustained-release capsule, which can prevent the rabeprazole sodium from being dissolved and damaged in gastric juice of a human body and improve the bioavailability.
The invention provides a dextro-rabeprazole sodium sustained-release capsule which is characterized in that: the sustained-release capsule comprises enteric pellets I and enteric pellets II, wherein the dextro-rabeprazole sodium accounts for 3-10% of the drug-containing pellet core, the stabilizing agent accounts for 3-10% of the drug-containing pellet core, and the disintegrating agent accounts for 3-10% of the drug-containing pellet core.
The formula of the dextro-rabeprazole sodium sustained-release capsule is as follows:
the medicine-containing pill core comprises the following components in parts by mass:
10-20 parts of dextro-rabeprazole sodium
10-20 parts of stabilizer
10-20 parts of solubilizer
Excipient 170 and 220 parts
10-20 parts of disintegrating agent
10-20 parts of adhesive
The isolating layer comprises the following components in parts by mass:
40-60 parts of adhesive
3-8 parts of opacifier
20-30 parts of anti-sticking agent
The enteric layer I comprises the following components in parts by mass:
10-20 parts of enteric material
5-12 parts of alkaline substance
5-10 parts of plasticizer
5-10 parts of anti-sticking agent
The enteric layer II comprises the following components in parts by mass:
10-20 parts of enteric material
1-3 parts of alkaline substance
5-10 parts of plasticizer
5-10 parts of a plasticizer.
Wherein the stabilizer is any one of magnesium hydroxide, magnesium carbonate, sodium bicarbonate and sodium carbonate.
The solubilizer is any one of polyethylene glycol 6000, poloxamer 188 and tween 80.
The excipient is any one of starch, sodium carboxymethyl starch, pregelatinized starch, microcrystalline cellulose, mannitol, lactose and sucrose.
The disintegrant is any one of croscarmellose sodium, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch.
The adhesive is one of polyvinylpyrrolidone, hypromellose, hyprolose and methylcellulose.
The antisticking agent is one of magnesium stearate, stearic acid, talcum powder and superfine silica gel powder.
The enteric material is the Eudragit S100, i.e., methacrylic acid and ethyl acrylate (1:2) polymer.
The alkaline substance is any one of aqueous sodium hydroxide solution (1mol/L), aqueous potassium hydroxide solution (1mol/L) and ammonia water (17% W/W).
The plasticizer is any one of triethyl citrate, tween 80 and polyethylene glycol 6000.
The invention provides a dextro-rabeprazole sodium sustained-release capsule which is characterized in that: the enteric materials used in the enteric layers of the enteric pellets I and II are Ewing S100, and the alkaline substances with different dosages are added to neutralize carboxyl groups with different molar numbers in the polymer so as to dissolve the carboxyl groups at different pH values, thereby achieving two-time release, wherein the dosage of the alkaline substances in the enteric layer of the enteric pellets I is 50-60% of the mass of the Ewing S100, and the dosage of the alkaline substances in the enteric layer of the enteric pellets II is 10-15% of the mass of the Ewing S100.
The invention provides a preparation method of a dextro-rabeprazole sodium sustained-release capsule, which comprises the following preparation process steps:
(1) preparing a medicine-containing pill core: placing the sucrose pill core of 30-40 meshes in a centrifugal granulating and coating pan, spraying an adhesive, adjusting machine parameters, centrifugally powdering, drying the pill in a fluidized bed at 40 ℃, and sieving to obtain the sucrose pill core;
(2) coating an isolation layer: weighing the adhesive, the opacifier and the anti-sticking agent according to the prescription, adding the adhesive, the opacifier and the anti-sticking agent into water, and uniformly stirring the mixture by using a homogenizer; adding the pill core containing the medicine into a multifunctional coating granulator, and atomizing and spraying the coating solution of the isolation layer for coating to obtain pellets containing the isolation layer;
(3) coating an enteric layer I: diluting Ewing S100 with water, dropwise adding a prescribed amount of alkaline substance, alkalifying for 40min, then pouring plasticizer and anti-sticking agent while stirring, homogenizing for 20-30min with a homogenizer, adding the pellets partially coated with the isolating layer into a multifunctional coating granulator, and spray-coating the enteric coating solution to obtain enteric pellets I;
(4) coating an enteric layer II: diluting Ewing S100 with water, dropwise adding a prescribed amount of alkaline substance, alkalifying for 40min, then pouring plasticizer and anti-sticking agent while stirring, homogenizing for 20-30min with a homogenizer, adding the pellets partially coated with the isolating layer into a multifunctional coating granulator, and spray-coating enteric coating solution to obtain enteric pellets II;
(5) and (3) calculating the content of the enteric pellets I and II by the content of the dextro-rabeprazole sodium according to the ratio of 1:3 weight portions are weighed and then filled into gelatin capsules.
The D-rabeprazole sodium sustained-release capsule prepared by the preparation method provided by the invention releases less than 5% in a medium with a pH value of 1.2 for 2 hours, then releases more than 25% in a medium with a pH value of 7.0 after accumulating for 2.5 hours, and releases more than 80% in a medium with an accumulating time of 5 hours. Therefore, the D-rabeprazole sodium can be prevented from being damaged in gastric acid, and can be released in the intestinal tract in a positioning manner, and the bioavailability is improved.
In conclusion, the product prepared according to the invention is hardly released in gastric acid and can be disintegrated in intestines to dissolve the active ingredient, thereby avoiding the damage of the rabeprazole sodium in gastric acid. Compared with a product DexPure on the market, the enteric-coated pellet contains 2 different types of enteric-coated pellets, the enteric-coated layer in the invention adopts the Eudragit S100, and different amounts of alkaline substances are added in the process of preparing the Eudragit S100 water dispersion to neutralize carboxyl groups with different molar numbers in the polymer and control the enteric-coated material to be dissolved under different pH values, so that the double controlled release (DDR) effect of 2 times of drug release is realized, the production cost is reduced, and the production process is simplified. Because the invention adopts the aqueous dispersion coating, the production safety is greatly improved, and the pollution to the environment is reduced, thereby effectively avoiding the problem of ethanol residue.
Detailed Description
The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto.
Example 1
The preparation process comprises the following steps:
weighing the raw materials and the auxiliary materials according to the prescription amount, sieving the raw materials and the auxiliary materials by a 80-mesh sieve for three times, and uniformly mixing the raw materials and the auxiliary materials. 200g of sucrose pill cores (30-40 meshes) are placed in a centrifugal granulation coating pan, 3 percent of hydroxypropyl methylcellulose aqueous solution is sprayed, and machine parameters are adjusted for centrifugal powdering. And after powdering, drying the pellets in a fluidized bed at 40 ℃ for 2h, and sieving to obtain the pellet.
Example 2
The preparation process comprises the following steps:
weighing the hydroxypropyl methylcellulose with the prescription amount, fully swelling in water, adding talcum powder and titanium dioxide, and uniformly stirring to obtain the coating liquid. 500g of the pellets obtained in example 1 were placed in a fluidized bed and coated. And (4) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 1h to obtain the coating.
Example 3
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding ammonia water (about 10min in use), continuously stirring for 30min after dropwise adding, and adding triethyl citrate and talcum powder for later use. 200g of the pellets obtained in example 2 were taken in a fluidized bed and coated. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 4
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding ammonia water (about 10min in use), continuously stirring for 30min after dropwise adding, and adding triethyl citrate and talcum powder for later use. 200g of the pellets obtained in example 2 were taken in a fluidized bed and coated. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 5
Pellets I obtained in example 3 and pellets II obtained in example 4 were weighed in a ratio of 1:3 by weight based on the content of D-rabeprazole sodium and filled into gelatin capsules. The filled capsules were subjected to a release test: the release test is carried out in pH1.2 for acid resistance 2h and then in pH7.0 medium. The results are shown in the following table.
From the above results, it can be seen that the self-prepared sample has good acid resistance, realizes dual controlled release effects in the medium of ph7.0, and does not contain ethanol residue.
Example 6
The preparation process comprises the following steps:
weighing the raw materials and the auxiliary materials according to the prescription amount, sieving the raw materials and the auxiliary materials by a 80-mesh sieve for three times, and uniformly mixing the raw materials and the auxiliary materials. 200g of sucrose pill cores (30-40 meshes) are placed in a centrifugal granulation coating pan, 3 percent of hydroxypropyl methylcellulose aqueous solution is sprayed, and machine parameters are adjusted for centrifugal powdering. And after powdering, drying the pellets in a fluidized bed at 40 ℃ for 2h, and sieving to obtain the pellet.
Example 7
The preparation process comprises the following steps:
weighing hydroxypropyl methylcellulose with the prescription amount, fully swelling in water, adding micro-powder silica gel, and uniformly stirring titanium dioxide to obtain the coating solution. 500g of the pellets obtained in example 6 were placed in a fluidized bed and coated. And (4) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 1h to obtain the coating.
Example 8
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding sodium hydroxide solution (about 10min in use), stirring for 30min after dropwise adding, and adding PEG6000 and silica gel micropowder for later use. 200g of the pellets obtained in example 7 were taken in a fluidized bed and coated. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 9
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding sodium hydroxide solution (about 10min in use), stirring for 30min after dropwise adding, and adding PEG6000 and silica gel micropowder for later use. 200g of the pellets obtained in example 7 were taken in a fluidized bed and coated. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 10
Pellets I obtained in example 8 and pellets II obtained in example 9 were weighed in a ratio of 1:3 by weight based on the content of D-rabeprazole sodium and filled into gelatin capsules. The filled capsules were subjected to a release test: the release test is carried out in pH1.2 for acid resistance 2h and then in pH7.0 medium. The results are shown in the following table.
From the above results, it can be seen that the self-prepared sample has good acid resistance, realizes dual controlled release effects in the medium of ph7.0, and does not contain ethanol residue.
Example 11
The preparation process comprises the following steps:
weighing the raw materials and the auxiliary materials according to the prescription amount, sieving the raw materials and the auxiliary materials by a 80-mesh sieve for three times, and uniformly mixing the raw materials and the auxiliary materials. 200g of sucrose pill core (30-40 meshes) is placed in a centrifugal granulating and coating pan, 3 percent of methyl cellulose aqueous solution is sprayed, and machine parameters are adjusted for centrifugal powdering. And after powdering, drying the pellets in a fluidized bed at 40 ℃ for 2h, and sieving to obtain the pellet.
Example 12
The preparation process comprises the following steps:
weighing the hydroxypropyl methylcellulose with the prescription amount, fully swelling in water, adding talcum powder and titanium dioxide, and uniformly stirring to obtain the coating liquid. 500g of the pellets obtained in example 11 were placed in a fluidized bed and coated. And (4) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 1h to obtain the coating.
Example 13
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding potassium hydroxide solution (about 10min in use), stirring for 30min after dropwise adding, and adding Tween 80 and pulvis Talci for use. 160g of the pellets from example 12 were taken and placed in a fluidized bed for coating. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 14
The preparation process comprises the following steps:
weighing the Eudragit S100, adding a small amount of water, stirring for 5min, slowly dropwise adding potassium hydroxide solution (about 10min in use), stirring for 30min after dropwise adding, and adding Tween 80 and pulvis Talci for use. 160g of the pellets from example 12 were taken and placed in a fluidized bed for coating. And (5) after the coating is finished, continuously drying the pellets in a fluidized bed at 40 ℃ for 2h to obtain the coating.
Example 15
Pellets I obtained in example 14 and pellets II obtained in example 15 were weighed in a ratio of 1:3 by weight based on the content of D-rabeprazole sodium and filled into gelatin capsules. The filled capsules were subjected to a release test: the release test is carried out in pH1.2 for acid resistance 2h and then in pH7.0 medium. The results are shown in the following table.
From the above results, it can be seen that the self-prepared sample has good acid resistance, realizes dual controlled release effects in the medium of ph7.0, and does not contain ethanol residue.
Claims (6)
1. A dextro-rabeprazole sodium sustained-release capsule is characterized in that: the sustained-release capsule comprises enteric pellets I and enteric pellets II, wherein the dextro-rabeprazole sodium accounts for 3-10% of the weight of a drug-containing pellet core, the stabilizing agent accounts for 3-10% of the weight of the drug-containing pellet core, and the disintegrating agent accounts for 3-10% of the weight of the drug-containing pellet core.
2. The dexrabeprazole sodium sustained-release capsule of claim 1, wherein: the dextro-rabeprazole sodium sustained-release pellet comprises a drug-containing pellet core, an isolating layer, an enteric layer I or an enteric layer II from inside to outside in sequence, wherein: the medicine-containing pill core comprises the following components in parts by mass:
10-20 parts of dextro-rabeprazole sodium;
10-20 parts of a stabilizer;
10-20 parts of a solubilizer;
220 portions of excipient 170 and;
10-20 parts of a disintegrating agent;
10-20 parts of an adhesive;
the isolating layer comprises the following components in parts by mass:
40-60 parts of an adhesive;
3-8 parts of an opacifier;
20-30 parts of an anti-sticking agent;
the enteric layer I comprises the following components in parts by mass:
10-20 parts of enteric material;
5-12 parts of alkaline substances;
5-10 parts of a plasticizer;
5-10 parts of an anti-sticking agent;
the enteric layer II comprises the following components in parts by mass:
10-20 parts of enteric material;
1-3 parts of alkaline substances;
5-10 parts of a plasticizer;
5-10 parts of an anti-sticking agent.
3. The dexrabeprazole sodium sustained-release capsule according to claim 1 or 2, wherein: the enteric materials used in the enteric layers of the enteric pellets I and II are Ewing S100, and the alkaline substances with different dosages are added to neutralize carboxyl groups with different molar numbers in the polymer so as to dissolve the carboxyl groups at different pH values, thereby achieving two-time release, wherein the dosage of the alkaline substances in the enteric layer of the enteric pellets I is 50-60% of the mass of the Ewing S100, and the dosage of the alkaline substances in the enteric layer of the enteric pellets II is 10-15% of the mass of the Ewing S100.
4. The dexrabeprazole sodium sustained-release capsule of claim 2, wherein: the stabilizer is any one of magnesium hydroxide, magnesium carbonate, sodium bicarbonate and sodium carbonate; the solubilizer is any one of polyethylene glycol 6000, poloxamer 188 and tween 80; the excipient is any one of starch, sodium carboxymethyl starch, pregelatinized starch, microcrystalline cellulose, mannitol, lactose and sucrose; the disintegrating agent is any one of cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch; the adhesive is any one of polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose and methyl cellulose; the antisticking agent is one of magnesium stearate, stearic acid, talcum powder and superfine silica gel powder; the enteric material is Eudragit S100, i.e. methacrylic acid and ethyl acrylate (1:2) polymer; the alkaline substance is any one of sodium hydroxide aqueous solution (1mol/L), potassium hydroxide aqueous solution (1mol/L) and ammonia water; the plasticizer is any one of triethyl citrate, tween 80 and polyethylene glycol 6000.
5. The dexrabeprazole sodium sustained-release capsule of claim 2, wherein: the preparation process comprises the following steps:
(1) preparing a medicine-containing pill core: placing the sucrose pellet core of 30-40 meshes in a centrifugal granulating and coating pan, spraying adhesive, adjusting machine parameters, centrifuging and powdering, drying the pellet in a fluidized bed at 40 ℃, and sieving to obtain the final product;
(2) coating an isolation layer: weighing the adhesive, the opacifier and the anti-sticking agent according to the prescription, adding the adhesive, the opacifier and the anti-sticking agent into water, and uniformly stirring the mixture by using a homogenizer; adding the pill core containing the medicine into a multifunctional coating granulator, and atomizing and spraying the coating solution of the isolation layer for coating to obtain pellets containing the isolation layer;
(3) coating an enteric layer I: diluting Ewing S100 with water, adding alkaline substance dropwise according to the prescription amount for alkalizing for 40min, then pouring plasticizer and antisticking agent while stirring, homogenizing for 20-30min with homogenizer, adding the pellet partially coated with the isolation layer into multifunctional coating granulator, and spray coating enteric coating solution to obtain enteric pellet I;
(4) coating an enteric layer II: diluting Ewing S100 with water, adding alkaline substance dropwise according to the prescription amount for alkalizing for 40min, then pouring plasticizer and antisticking agent while stirring, homogenizing for 20-30min with homogenizer, adding the pellet partially coated with the isolation layer into multifunctional coating granulator, and spray coating enteric coating solution to obtain enteric pellet II;
(5) weighing the enteric pellets I and II according to the weight ratio of 1:3 based on the content of the dextro-rabeprazole sodium, and then filling the enteric pellets I and II into a gelatin capsule.
6. The dexrabeprazole sodium sustained-release capsule according to claim 1 or 2, wherein: the release rate of the sustained-release capsule is less than 5% in a medium with pH1.2 after 2 hours, and then the release rate is more than 25% in a medium with pH7.0 after 2.5 hours of accumulation, and the release rate is more than 80% in 5 hours of accumulation.
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| CN112796039A (en) * | 2020-12-30 | 2021-05-14 | 江苏大学 | Preparation method of pH intelligent response controlled-release antibacterial packaging fiber film |
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| CN103202818A (en) * | 2012-01-15 | 2013-07-17 | 山东新时代药业有限公司 | An enteric-coated tablet containing D-rabeprazole or a pharmaceutically acceptable salt thereof, and a preparation method therefor |
| CN103599087A (en) * | 2013-05-21 | 2014-02-26 | 海南海力制药有限公司 | Rabeprazole sodium enteric-coated pellet and preparation method thereof |
| CN104940169A (en) * | 2015-06-26 | 2015-09-30 | 山东省药学科学院 | Dexlansoprazole sustained release capsule and preparation method thereof |
| CN104997757A (en) * | 2015-07-16 | 2015-10-28 | 广东彼迪药业有限公司 | Rabeprazole sodium enteric-coated pellet capsule and preparation method thereof |
| CN105796532A (en) * | 2016-03-28 | 2016-07-27 | 中国医药集团总公司四川抗菌素工业研究所 | Rabeprazole sodium sustained-release capsule and preparation method thereof |
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| CN112796039A (en) * | 2020-12-30 | 2021-05-14 | 江苏大学 | Preparation method of pH intelligent response controlled-release antibacterial packaging fiber film |
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