CN115350158A - Vonoprazan fumarate gastric retention tablet and preparation method thereof - Google Patents
Vonoprazan fumarate gastric retention tablet and preparation method thereof Download PDFInfo
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- CN115350158A CN115350158A CN202211195597.0A CN202211195597A CN115350158A CN 115350158 A CN115350158 A CN 115350158A CN 202211195597 A CN202211195597 A CN 202211195597A CN 115350158 A CN115350158 A CN 115350158A
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to a stomach retention tablet containing vonoprazan fumarate, and provides the stomach retention tablet containing the vonoprazan fumarate, which comprises active components of vonoprazan fumarate, hydroxypropyl methylcellulose, sodium bicarbonate, polyethylene glycol, carnauba wax, mannitol and magnesium stearate. The gastric retention tablet provided by the invention has the advantages of simple composition, quick floating, long lasting floating time and simple process, avoids a damp-heat process, has more excellent product stability, has excellent sustained and controlled release characteristics, and slowly releases main drugs from the gastric retention tablet through dual mechanisms of diffusion and skeleton erosion.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a vonoprazan fumarate-containing gastric retention tablet and a preparation method thereof.
Background
Vonoprazan fumarate is a novel potassium ion competitive acid blocker (P-CAB), reversibly inhibits the activity of K +, K + -ATP enzyme in a competitive potassium ion mode, and achieves the effect of effectively inhibiting gastric acid secretion;
the gastric retention tablet is a tablet which can keep the density of the tablet to be less than the density of gastric contents after being taken orally and is in a floating state in gastric juice, a gastric floating preparation is retained in the stomach for a long time and is suitable for gastric treatment drugs or gastric acid secretion inhibitors, and the Vonoprazan fumarate gastric retention tablet can enable the main component to stay at the cell part of the gastric wall for a long time to inhibit the generation of gastric acid by prolonging the release time in the stomach; meanwhile, the prescription contains sodium bicarbonate, so that the stimulation of gastric acid to the stomach wall can be quickly neutralized, and the stomach pain caused by the gastric acid can be relieved to a great extent.
Therefore, it is of great significance to develop a method for preparing the gastric retention tablet with simple preparation process, stable and controllable process and high production efficiency, and to obtain a solid preparation with stable quality.
Disclosure of Invention
The object of the present invention is to provide a gastric retentive tablet containing vonoprazan fumarate, based on the prior art.
Another object of the present invention is to provide a method for preparing the above-mentioned vonoprazan fumarate-containing gastro-retentive tablet.
The technical scheme of the invention is as follows:
a gastric retention tablet containing vonoprazan fumarate comprises the active components of vonoprazan fumarate, hypromellose, sodium bicarbonate, polyethylene glycol, carnauba wax, mannitol and magnesium stearate.
The gastric retention tablet provided by the invention mainly comprises an active component vonoprazan fumarate, a hydrophilic gel material, a pore-forming agent, a foaming agent, a corrosion skeleton regulator, a lubricant, a filling agent and the like, wherein the hydrophilic gel material is preferably hydroxypropyl methylcellulose; the pore-forming agent is polyethylene glycol; the foaming agent is sodium bicarbonate; the corrosion skeleton regulator is carnauba wax; the lubricant is magnesium stearate; the bulking agent is mannitol.
In a preferred embodiment, the vonoprazan fumarate-containing gastric retention tablet provided by the invention comprises the following components in parts by weight: 10-15 parts of vonoprazan fumarate, 40-60 parts of hydroxypropyl methylcellulose, 10-20 parts of sodium bicarbonate, 1-10 parts of polyethylene glycol, 1-10 parts of carnauba wax, 10-20 parts of mannitol and 0.5-2 parts of magnesium stearate. The gastric retention tablet can also comprise other auxiliary materials, and other components in hydrophilic gel materials, pore-foaming agents, corrosion skeleton regulators, lubricants and fillers.
In a preferred scheme, the invention provides a vonoprazan fumarate-containing gastric retention tablet which is prepared from the following components in parts by weight: 10-15 parts of vonoprazan fumarate, 40-60 parts of hydroxypropyl methylcellulose, 10-20 parts of sodium bicarbonate, 1-10 parts of polyethylene glycol, 1-10 parts of carnauba wax, 10-20 parts of mannitol and 0.5-2 parts of magnesium stearate.
In another preferred scheme, the invention provides a vonoprazan fumarate-containing gastric retention tablet which is prepared from the following components in parts by weight: 10-15 parts of vonoprazan fumarate, 45-55 parts of hydroxypropyl methylcellulose, 10-16 parts of sodium bicarbonate, 3-8 parts of polyethylene glycol, 3-8 parts of carnauba wax, 10-17 parts of mannitol and 0.5-1.5 parts of magnesium stearate.
The active component of the tablets containing vonoprazan fumarate, which is provided by the invention, has the structural formula shown in the specification,
in a preferable scheme, the hypromellose is one or more of K4M, K15M, K100M and K200M, and is preferably a mixture of K4M and K100M. In a preferred scheme, the dosage ratio of hydroxypropyl methylcellulose K4M to K100M is 3: 7-6: 4, preferably 4: 6-5: 5.
in a preferable scheme, the polyethylene glycol is one or more of polyethylene glycol 4000, polyethylene glycol 6000 and polyethylene glycol 8000; preferably, the polyethylene glycol is polyethylene glycol 6000.
In a preferred embodiment, the vonoprazan fumarate-containing gastro-retentive tablet of the present invention is prepared from the following components in mass per 1000 formulation units: 20g of vonoprazan fumarate, 40g of hydroxypropyl methylcellulose K4M, 60g of carboxymethyl cellulose K100M, 30g of sodium bicarbonate, 10g of polyethylene glycol, 10g of carnauba wax, 2g of magnesium stearate and 28g of mannitol.
In a preferred embodiment, the vonoprazan fumarate-containing gastro-retentive tablet of the present invention is prepared from the following components in mass per 1000 formulation units: 20g of vonoprazan fumarate, 50g of hydroxypropyl methylcellulose K4M, 50g of carboxymethyl cellulose K100M, 30g of sodium bicarbonate, 10g of polyethylene glycol, 15g of carnauba wax, 2g of magnesium stearate and 23g of mannitol.
In a preferred embodiment, the vonoprazan fumarate-containing gastro-retentive tablet of the present invention is prepared from the following components in mass per 1000 formulation units: 20g of vonoprazan fumarate, 60g of hydroxypropyl methylcellulose K4M, 40g of carboxymethyl cellulose K100M, 20g of sodium bicarbonate, 10g of polyethylene glycol, 15g of carnauba wax, 2g of magnesium stearate and 33g of mannitol.
The invention also provides a preparation method of the vonoprazan fumarate-containing gastric retention tablet, which comprises the steps of uniformly mixing the active components vonoprazan fumarate, mannitol, hypromellose, sodium bicarbonate, polyethylene glycol 6000 and carnauba wax, finally adding magnesium stearate, mixing, tabletting and packaging.
In a preferred embodiment, the vonoprazan fumarate-containing gastric retention tablet of the present invention can be prepared as follows:
(1) Pretreatment: pulverizing the active components, sieving, and sieving other adjuvants;
(2) Mixing: uniformly mixing the pretreated active component and auxiliary materials (except for a lubricant), and finally adding magnesium stearate for mixing;
(3) Tabletting: directly tabletting the mixed powder obtained after premixing, and controlling the hardness: 30-50N.
In a preferred embodiment, in step (1), the active ingredient vonoprazan fumarate has a particle size d90 after pulverization of <200 μm; the active components are crushed and then screened by a 60-100 mesh sieve.
The invention also provides a preparation method of the Vonoprazan fumarate-containing gastric retention tablet, which comprises the following steps:
(1) Pretreatment: pulverizing the active components, sieving, and sieving other adjuvants;
(2) Premixing: mixing pretreated active components, mannitol (SD 200), hypromellose (K100M, K4M), sodium bicarbonate, polyethylene glycol 6000, and carnauba wax, and adding magnesium stearate;
(3) Tabletting: directly tabletting the mixed powder obtained after premixing, using a shallow concave punch with the diameter of 8.0mm, and controlling the hardness: 30-50N;
by adopting the technical scheme of the invention, the advantages are as follows:
(1) The vonoprazan fumarate gastric retention tablet prepared by the method is simple in composition, quick in floating and long in lasting floating time, two hydrophilic gel materials of hydroxypropyl cellulose K100M and K4M are selected, carnauba wax is added to serve as an erosion protective agent, the defect that a conventional effervescent gastric retention tablet is easy to break and split is overcome, and polyethylene glycol is used as a pore-forming agent, so that the active ingredients in the formula can be continuously and slowly released; in addition, the sodium bicarbonate in the composition not only can enhance the floating and slow-release effects, but also can quickly neutralize gastric acid, and has very obvious relieving effect on the stomachache caused by the hyperacidity.
(2) The Vonoprazan fumarate gastric retention tablet prepared by the method has the advantages of simple process, avoidance of damp-heat process and more excellent product stability.
(3) The Vonoprazan fumarate gastric retention tablet prepared by the method has excellent sustained and controlled release characteristics, and the main drug is slowly released from the gastric retention tablet through dual mechanisms of diffusion and skeleton erosion.
Detailed Description
The tablets and their preparation according to the invention are further illustrated by the following examples, which are not intended to limit the invention in any way.
Example 1
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=131.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 60-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax (fine powder type), sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing (20rpm, 3min);
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
example 2
Tablet formulation (1000 formulation unit weight):
＊ after the active components are crushedParticle size d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Premixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax (fine powder type), sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, xiao Lun, zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
example 3
Tablet formulation (1000 formulation unit amount):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax (fine powder type), sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing (20rpm, 3min);
(3) Tabletting: adopting a rotary tablet machine (ZP 10A, beijing national medicine Longli), a circular shallow concave punch with the diameter of 8.0mm for tabletting, and the hardness is 30-50N;
comparative example 1
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredient with mannitol SD200, hypromellose K100M, carnauba wax (fine powder type), sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
comparative example 2
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Premixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, calgon, zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
comparative example 3
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax, and polyethylene glycol 6000 in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet machine (ZP 10A, beijing national medicine Longli), a circular shallow concave punch with the diameter of 8.0mm for tabletting, and the hardness is 30-50N;
comparative example 4
Tablet formulation (1000 formulation unit amount):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, and sodium bicarbonate in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
comparative example 5
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Pre-mixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax, sodium bicarbonate, and sodium chloride in hopper mixer (HLS-10, conn. Zhejiang), adding magnesium stearate, and mixing at 20rpm, 3min;
(3) Tabletting: adopting a rotary tablet machine (ZP 10A, beijing national medicine Longli), a circular shallow concave punch with the diameter of 8.0mm for tabletting, and the hardness is 30-50N;
comparative example 6
Tablet formulation (1000 formulation unit weight):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Premixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, sodium alginate, sodium bicarbonate, and polyethylene glycol 6000 in hopper mixer (HLS-10, town, cal.) at 20rpm, 10min), and adding magnesium stearate to mix at 20rpm, 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
comparative example 7
Tablet formulation (1000 formulation unit amount):
＊ the particle size of the active component after being crushed is d90=43.0 μm; mannitol for regulating tablet weight to 200mg
The preparation method comprises the following steps:
(1) Pretreatment: pulverizing the active ingredients by a universal pulverizer, sieving with a 100-mesh sieve for later use, and sieving other auxiliary materials for later use;
(2) Premixing: mixing the active ingredients with mannitol SD200, hypromellose K100M, hypromellose K4M, carnauba wax, sodium lauryl sulfate, and polyethylene glycol 6000 in hopper mixer (HLS-10, xiao Lun, zhejiang), adding magnesium stearate, and mixing at 20rpm and 3min;
(3) Tabletting: adopting a rotary tablet press (ZP 10A, beijing national medicine Longli), and pressing by using a circular shallow concave punch with the diameter of 8.0mm, wherein the hardness is 30-50N;
as can be seen from the comparison of the table 2, the in vitro drug release of the drugs in the examples 1, 2 and 3 is mild, the drug release is about 15 to 20 percent in 1 hour, about 60 percent in 6 hours and about 95 percent in 12 hours, and the main drug is slowly released from the gastric retention tablets through dual mechanisms of diffusion and skeleton erosion. In comparative example 1, HPMC K100M is adopted alone, the drug release is incomplete, and a hard core still exists after 12 hours, probably because HPMC K100M belongs to a hydrophilic material with higher viscosity, and when the HPMC K100M is used in a large amount, the floating time of the tablet is ensured, but the drug release is retarded; in comparative example 2, no carnauba wax was used, and in the present invention, about 15% sodium bicarbonate was used, and bubbles were generated to help the floating of the tablet by the action of gastric acid, but the tablet without carnauba wax as a skeleton erosion material was easily broken due to the invasion of water and the impact of bubbles, and the dissolution of the tablet was rapidly increased, and the floating and sustained-release effects could not be maintained. In comparative example 3, sodium hydrogencarbonate was not used, the rising time was significantly prolonged, and the dissolution was insufficient. Comparative example 4 does not add the porogen polyethylene glycol 6000, also causes insufficient dissolution; in comparative example 5, inorganic salt NaCl is used as a pore-forming agent, which may cause that the water penetration speed is faster, so that the drug release is faster and the effect of slow and sustained release cannot be obtained; in comparative example 6, sodium alginate is used as a corrosion skeleton regulator, which may be a reason for hydrophobicity and viscosity, and causes the problem that the floating sheet is broken after 6 hours, so that the dissolution is increased rapidly; in comparative example 7, sodium lauryl sulfate is used as a foaming agent, the initial foam amount is insufficient, the rising and floating time is obviously prolonged, and in the later period, a layer of fine active agent bubbles are gathered on the surface of the tablet (the bubbles are large in amount and not easy to break), so that moisture is indirectly isolated, and the moisture enters the tablet core slowly and is not dissolved sufficiently.
The above results show that the product quality is better when the particle size range of the active ingredient is <200 μm d 90.
The above examples are only intended to illustrate the technical solution of the present invention, and not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: modifications of the technical solutions described in the foregoing embodiments are still possible, or some technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. The stomach retention tablet containing vonoprazan fumarate is characterized by comprising the active components of vonoprazan fumarate, hypromellose, sodium bicarbonate, polyethylene glycol, carnauba wax, mannitol and magnesium stearate.
2. The vonoprazan fumarate-containing gastro-retentive tablet of claim 1, comprising the following components in parts by weight: 10-15 parts of vonoprazan fumarate, 40-60 parts of hydroxypropyl methylcellulose, 10-20 parts of sodium bicarbonate, 1-10 parts of polyethylene glycol, 1-10 parts of carnauba wax, 10-20 parts of mannitol and 0.5-2 parts of magnesium stearate.
3. The vonoprazan fumarate-containing gastro-retentive tablet of claim 1, which is prepared from the following components in parts by weight: 10-15 parts of vonoprazan fumarate, 45-55 parts of hydroxypropyl methylcellulose, 10-16 parts of sodium bicarbonate, 3-8 parts of polyethylene glycol, 3-8 parts of carnauba wax, 10-17 parts of mannitol and 0.5-1.5 parts of magnesium stearate.
4. Vonoprazan fumarate-containing gastro-retentive tablet according to claim 1, wherein the hypromellose is one or more of K4M, K15M, K100M, K200M, preferably a mixture of K4M and K100M.
5. The vonoprazan fumarate-containing gastro-retentive tablet of claim 1, wherein the polyethylene glycol is one or more of polyethylene glycol 4000, polyethylene glycol 6000 and polyethylene glycol 8000; preferably, the polyethylene glycol is polyethylene glycol 6000.
6. The vonoprazan fumarate-containing gastro-retentive tablet of any one of claims 1 to 5, wherein the tablet is made of the following components in mass per 1000 units of formulation: 20g of vonoprazan fumarate, 40-60 g of hydroxypropyl methylcellulose K4M, 40-60 g of carboxymethyl cellulose K100M, 20-30 g of sodium bicarbonate, 10g of polyethylene glycol, 10-15 g of carnauba wax, 2g of magnesium stearate and mannitol for adjusting the total weight to 200g.
7. The vonoprazan fumarate-containing gastric retention tablet as claimed in claim 1, wherein the active ingredients vonoprazan fumarate, mannitol, hypromellose, sodium bicarbonate, polyethylene glycol 6000, and carnauba wax are mixed uniformly in the preparation process, and finally magnesium stearate is added for mixing, tabletting, and packaging to obtain the product.
8. The pinorubin fumarate-containing gastro-retentive tablet of claim 1, comprising the steps of:
(1) Pretreatment: pulverizing the active components, sieving, and sieving other adjuvants;
(2) Mixing: uniformly mixing the pretreated active component and other auxiliary materials except magnesium stearate, and finally adding magnesium stearate for mixing;
(3) Tabletting: directly tabletting the mixed powder obtained after premixing, and controlling the hardness: 30N-50N.
9. The Vonoprazan fumarate-containing gastro-retentive tablet of claim 6, wherein in step (1), the active ingredient Vonoprazan fumarate has a particle size d90 after crushing of <200 μm; the active components are crushed and then screened by a 60-100 mesh sieve.
10. The method for preparing a vonoprazan fumarate-containing gastro-retentive tablet of claim 1, comprising the steps of:
(1) Pretreatment: pulverizing the active components, sieving, and sieving other adjuvants;
(2) Mixing: uniformly mixing the pretreated active component and the auxiliary materials (except the lubricant), and finally adding magnesium stearate for mixing;
(3) Tabletting: directly tabletting the mixed powder obtained after premixing, and controlling the hardness: 30-50N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211195597.0A CN115350158B (en) | 2022-09-28 | 2022-09-28 | Gastric retention tablet of voronoi fumarate and preparation method thereof |
Applications Claiming Priority (1)
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| CN202211195597.0A CN115350158B (en) | 2022-09-28 | 2022-09-28 | Gastric retention tablet of voronoi fumarate and preparation method thereof |
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Citations (6)
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| WO2008101375A1 (en) * | 2007-02-16 | 2008-08-28 | Guangzhou Pui's Pharmaceutical Factory Ltd. | A gastric retentive sustained-release pharmaceutical composition comprising irbesartan |
| CN105106203A (en) * | 2015-08-17 | 2015-12-02 | 江苏豪森药业股份有限公司 | Pharmaceutical composition with vonoprazan fumarate and preparation method thereof |
| CN106074431A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate preparation and application thereof |
| CN106074429A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate effervescent tablet and preparation method thereof |
| CN111973565A (en) * | 2020-07-07 | 2020-11-24 | 南京海纳医药科技股份有限公司 | Vonoprazan fumarate-containing tablet and dissolution rate determination method thereof |
| CN112237572A (en) * | 2020-10-28 | 2021-01-19 | 海南卫康制药(潜山)有限公司 | Vonoprazan fumarate tablet and preparation method thereof |
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| WO2008101375A1 (en) * | 2007-02-16 | 2008-08-28 | Guangzhou Pui's Pharmaceutical Factory Ltd. | A gastric retentive sustained-release pharmaceutical composition comprising irbesartan |
| CN105106203A (en) * | 2015-08-17 | 2015-12-02 | 江苏豪森药业股份有限公司 | Pharmaceutical composition with vonoprazan fumarate and preparation method thereof |
| CN106074431A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate preparation and application thereof |
| CN106074429A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate effervescent tablet and preparation method thereof |
| CN111973565A (en) * | 2020-07-07 | 2020-11-24 | 南京海纳医药科技股份有限公司 | Vonoprazan fumarate-containing tablet and dissolution rate determination method thereof |
| CN112237572A (en) * | 2020-10-28 | 2021-01-19 | 海南卫康制药(潜山)有限公司 | Vonoprazan fumarate tablet and preparation method thereof |
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