CN107744509B - Mosapride citrate tablet and preparation method thereof - Google Patents
Mosapride citrate tablet and preparation method thereof Download PDFInfo
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- CN107744509B CN107744509B CN201711001305.4A CN201711001305A CN107744509B CN 107744509 B CN107744509 B CN 107744509B CN 201711001305 A CN201711001305 A CN 201711001305A CN 107744509 B CN107744509 B CN 107744509B
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- mosapride citrate
- hydroxypropyl methylcellulose
- lactose
- starch
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- YPELFRMCRYSPKZ-UHFFFAOYSA-N 4-amino-5-chloro-2-ethoxy-N-({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)benzamide Chemical compound CCOC1=CC(N)=C(Cl)C=C1C(=O)NCC1OCCN(CC=2C=CC(F)=CC=2)C1 YPELFRMCRYSPKZ-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 229960004085 mosapride Drugs 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title abstract description 20
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 30
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 30
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 30
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000463 material Substances 0.000 claims abstract description 19
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 17
- 239000008101 lactose Substances 0.000 claims abstract description 17
- 229920002472 Starch Polymers 0.000 claims abstract description 14
- 239000008107 starch Substances 0.000 claims abstract description 14
- 235000019698 starch Nutrition 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000005550 wet granulation Methods 0.000 claims abstract description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 17
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 16
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 16
- 239000000741 silica gel Substances 0.000 claims description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims description 15
- 239000008213 purified water Substances 0.000 claims description 12
- 238000007873 sieving Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 10
- 238000005303 weighing Methods 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 9
- 229910021487 silica fume Inorganic materials 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 abstract description 27
- 239000003814 drug Substances 0.000 abstract description 19
- 239000012752 auxiliary agent Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 230000030135 gastric motility Effects 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 36
- 229960001375 lactose Drugs 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 238000000034 method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 229960003943 hypromellose Drugs 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 229960000913 crospovidone Drugs 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 4
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 3
- 201000006549 dyspepsia Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229960004977 anhydrous lactose Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940049654 glyceryl behenate Drugs 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 2
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 229940057948 magnesium stearate Drugs 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 229960004274 stearic acid Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000007939 sustained release tablet Substances 0.000 description 2
- LRZSAGKIMYFLHY-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;dihydrate Chemical compound O.O.OC(=O)CC(O)(C(O)=O)CC(O)=O LRZSAGKIMYFLHY-UHFFFAOYSA-N 0.000 description 1
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- 108091005482 5-HT4 receptors Proteins 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
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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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- 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
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The application relates to a mosapride citrate tablet and a preparation method thereof, belonging to the technical field of medical organic active ingredient-containing pharmaceutical preparations. The mosapride citrate tablet is prepared by using mosapride citrate as a raw material, lactose, starch and hydroxypropyl methylcellulose as auxiliary materials and adding an auxiliary agent, and performing wet granulation and tabletting. The application is applied to the preparation of the gastric motility medicine, and has the advantages of rapid dissolution, good stability, simple preparation process, easy industrialized mass production and the like.
Description
Technical Field
The application relates to a mosapride citrate tablet and a preparation method thereof, belonging to the technical field of medical organic active ingredient-containing pharmaceutical preparations.
Background
Mosapride citrate is a third-generation gastric motility drug developed by Japanese pharmaceutical corporation, is a selective 5-HT4 receptor agonist, belongs to the third-generation gastric motility drug, and is mainly used for treating functional dyspepsia and gastroesophageal reflux disease. The composition can obviously improve symptoms of acid development and heartburn of patients with functional dyspepsia, accelerate gastric emptying, and promote gastric and duodenal motility. Meanwhile, the medicament has no side effects such as extrapyramidal system reaction, diarrhea and the like, and has good tolerance.
The chemical name of the mosapride citrate is (+/-) -4-amino-5-chloro-2-ethoxy-N- { [4- (4-fluorobenzyl) -2-morphinyl]Methyl toluamide citrate dihydrate having the formula: c21H25ClFN3O3·C6H8O7·2H2O, molecular weight 650.05, structural formula:
the existing formulations of the mosapride citrate comprise sustained-release tablets, sustained-release capsules and oral solutions. Although these techniques are relatively mature, they still have a number of disadvantages. Mosapride citrate tablets are approved to be marketed in China in 1999, and the clinical use specifications are 2.5mg and 5 mg. After the oral solid preparation enters the body, the oral solid preparation can be absorbed by the organism through a biological membrane after being dissolved out. According to the current national standard WSI- (X-287) -2003Z, the dissolution rate of the mosapride citrate tablet in 0.1mol/L hydrochloric acid solution is not lower than 75% in 30 min; the registration standard JX20080288 of the imported drugs specifies that the dissolution rate of the mosapride citrate in phosphate buffered saline with the pH value of 6.8 is not lower than 80 percent in 45 min. However, as the mosapride citrate is a BCS II medicament and has extremely low solubility in water, the problem of low dissolution rate or even unqualified dissolution rate is often encountered in the practical production of the mosapride citrate oral solid preparation. It is very practical to solve the problem of low bioavailability of insoluble drugs caused by poor solubility and slow dissolution rate.
Chinese patent with publication No. CN101273973B discloses a pharmaceutical composition containing mosapride citrate prepared by directly tabletting powder and a preparation method thereof. The tablets prepared by the patent technology can be quickly disintegrated, but for insoluble medicines, the medicines can not be dissolved in a dissolving medium after being quickly disintegrated.
Chinese patent with publication number CN102335154A discloses a mosapride citrate sustained-release tablet, which has a sustained-release effect for 12 hours and consists of mosapride citrate, a sustained-release material, a diluent, an adhesive, a lubricant and a coating material. The slow release tablet is influenced by a plurality of factors such as pressure, powder fluidity and the like when being compressed, and brings a plurality of difficulties for the investigation of the optimal process in the later period.
The present application was made based on this.
Disclosure of Invention
In view of the defects of the prior art, the application firstly provides the mosapride citrate tablet which has simple process, quick dissolution and stable quality.
In order to achieve the purpose, the technical scheme adopted by the application is as follows:
the mosapride citrate tablet comprises the following components in parts by weight:
further, as preferable:
the lactose is anhydrous lactose.
The lubricant is selected from one or more of glyceryl palmitostearate, glyceryl behenate, glyceryl monostearate, stearic acid and magnesium stearate, and is preferably magnesium stearate.
The disintegrant is selected from one or more of low-substituted hydroxypropyl cellulose, microcrystalline cellulose and crospovidone, and is preferably low-substituted hydroxypropyl cellulose.
The glidant is one or more of talcum powder and micro silica gel, and the micro silica gel is preferred.
The preparation method of the mosapride citrate tablet with the characteristics comprises the following steps of taking mosapride citrate as a raw material, taking lactose, starch and hydroxypropyl methylcellulose as auxiliary materials, and adding an auxiliary agent to prepare the mosapride citrate tablet:
1) weighing raw and auxiliary materials according to the prescription amount, and sieving the auxiliary materials with a 60-mesh sieve for later use;
2) weighing purified water according to the prescription amount, adding hydroxypropyl methylcellulose according to the prescription amount, and stirring and dissolving to form a hydroxypropyl methylcellulose aqueous solution;
3) lactose, API (i.e. raw materials: mosapride citrate), starch and hydroxypropyl methylcellulose water solution are premixed and then granulated by a wet method;
4) drying the particles formed in the step (3), sieving the particles with a 30-mesh sieve, grading, and adding an auxiliary agent for total mixing;
5) and (6) tabletting.
Further, as preferable:
in the step (2), the adding mass ratio of the purified water to the hydroxypropyl methylcellulose is 6-10: 1. During the production process, we have unexpectedly found that: the hypromellose is dissolved in water, the water solution is used as an adhesive, the adhesive effect is good, especially when the mesh number of the hypromellose is not more than 60 meshes, and the mixing ratio of purified water and the hypromellose is controlled at 8:1, the hypromellose water solution has surface activity, so that the hypromellose water solution has good dispersibility and cohesiveness, and then subsequent granulation, drying, granule finishing and tabletting are carried out on the basis, so that the mosapride citrate tablet with stable drug property can be obtained.
The auxiliary agents comprise a lubricant, a disintegrating agent and a flow aid, and the auxiliary agents are arranged and used for adjusting the overall uniformity and the dispersity of the tablet.
More preferably:
the lubricant is selected from one or more of glyceryl palmitostearate, glyceryl behenate, glyceryl monostearate, stearic acid and magnesium stearate, and is preferably magnesium stearate.
The disintegrating agent is selected from one or more of low-substituted hydroxypropyl cellulose, microcrystalline cellulose and crospovidone, and preferably the low-substituted hydroxypropyl cellulose. The selected disintegrant, especially low-substituted hydroxypropyl cellulose, has larger surface area and porosity, so that the disintegrant can quickly absorb water and expand, when the disintegrant is used for tabletting of the tablets, the tablets can be quickly disintegrated, and the coarse structure of the disintegrant is greatly embedded with the medicines and the granules, so that the hardness of the tablets can be obviously improved, and the disintegration is not influenced, thereby accelerating the dissolution of the medicines and improving the bioavailability.
The glidant is one or more of talcum powder and micro silica gel, and the micro silica gel is preferred. The glidant can reduce the friction between particles and granules and between tablets and the wall of a die hole and endow the tablets with smooth and attractive surface, when one or a mixture of talcum powder and micro silica gel is selected as the glidant, particularly when the micro silica gel is selected as the glidant, the flowability of the particles can be improved, the tablets have smooth and attractive surface effect, when the water absorption capacity reaches 40 percent of the self weight, the powder state can be still kept, the tablets can still be effectively thickened in non-polar and low-polar media, and the stability of the active ingredients of the medicaments wrapped in the tablets is improved.
Therefore, compared with the prior art, the mosapride citrate tablet provided by the application has the following advantages and remarkable progresses:
(1) the medicine is dissolved out quickly and has stable quality. The mosapride citrate tablet mainly comprises three parts, namely a raw material, an auxiliary material and an auxiliary agent, wherein the raw material exists as a pharmaceutical active ingredient, in the auxiliary material, hypromellose is mixed with water and then used as an adhesive to be mixed with the raw material and other components, and the tablet inner core is endowed with good physical stability and drug property stability under the coordination of lactose (the lactose is preferably anhydrous lactose) and starch; then the granules formed by the raw materials and the auxiliary materials are mixed with the auxiliary agent and tabletted, and the tablet is matched with the inner core while keeping the smoothness and hardness of the tablet, so that the good dissolution of the tablet is ensured.
(2) The preparation method is simple, the requirement on the granularity is not strict, complex preparation equipment is not needed, and the industrial mass production is easy to realize. In the preparation process of the tablet, the method mainly comprises four steps: the hydroxypropyl methylcellulose is water-soluble, the raw materials and the auxiliary materials are premixed and granulated (forming an inner core), the inner core and the auxiliary agents are mixed together and tabletted, except the requirement of the mesh number of the auxiliary materials and granules, other components do not have a strict requirement on the strength, and equipment involved in the whole processing process only has a wet granulator in a granulating process and a tablet machine in a tabletting process, so that complicated on-machine equipment is not needed, the process has strong universality, and the industrialized production is facilitated.
Drawings
FIG. 1 is a pH6.8 dissolution profile.
Detailed Description
The following examples are further illustrated, but are only illustrative of the most preferred embodiments and the disclosure is not limited thereto.
In the following embodiments, mosapride citrate is available from pharmaceutical industry Co., Ltd of New time in Shandong, and has a specification of 15 μm; lactose was purchased from DFE Pharma with a specification of 200 mesh; starch is purchased from Jiaxing Bailang starch products, Inc., and is corn starch; the low-substituted hydroxypropyl cellulose is purchased from Anhui mountain river pharmaceutic adjuvant, Inc.; hydroxypropyl methylcellulose is available from Nippon Caoda corporation as model number LF; purified water was prepared from Zhejiang Angerican pharmaceuticals, Inc.; magnesium stearate is purchased from Anhui mountain river pharmaceutic adjuvant, Inc.; silica gel micropowder was purchased from Anhui mountain river pharmaceutic adjuvant, Inc.
And (3) wet granulating machine: chongqing Engel granulation coating technology, Inc., model EMG 2-6.
Example 1
Mosapride citrate 26.50g
Lactose 295.00g
160.00g of starch
Low-substituted hydroxypropylcellulose 140.00g
Hydroxypropyl methylcellulose 12.00g
Purified water 188.00g
Magnesium stearate 6.50g
8.25g of silica gel micropowder.
The preparation method comprises the following steps:
1) weighing raw and auxiliary materials according to the prescription amount, and sieving the auxiliary materials with a 60-mesh sieve;
2) weighing purified water according to the prescription amount, adding hydroxypropyl methylcellulose according to the prescription amount, stirring and dissolving, and stirring and dissolving to form a hydroxypropyl methylcellulose aqueous solution;
3) transferring lactose, API, starch and the hydroxypropyl methylcellulose water solution formed in the step (2) into a wet granulator in sequence, and carrying out wet granulation after premixing;
4) drying, sieving with 30 mesh sieve, grading, and mixing low-substituted hydroxypropyl cellulose, magnesium stearate and silica gel micropowder;
5) and (6) tabletting.
Example 2
Mosapride citrate 26.50g
Lactose 300.00g
Starch 150.00g
Low-substituted hydroxypropylcellulose 155.00g
Hydroxypropyl methylcellulose 15.00g
Purified water 188.00g
Magnesium stearate 6.50g
8.00g of silica gel micropowder.
The preparation method comprises the following steps:
1) weighing raw and auxiliary materials according to the prescription amount, and sieving the auxiliary materials with a 60-mesh sieve;
2) weighing purified water according to the prescription amount, adding hydroxypropyl methylcellulose according to the prescription amount, and stirring and dissolving to form a hydroxypropyl methylcellulose aqueous solution;
3) transferring lactose, API, starch and the hydroxypropyl methylcellulose water solution formed in the step (2) into a wet granulator in sequence, and carrying out wet granulation after premixing;
4) drying, sieving with 30 mesh sieve, grading, and mixing low-substituted hydroxypropyl cellulose, magnesium stearate and silica gel micropowder; 5) and (6) tabletting.
Comparative example 1
Mosapride citrate 75.00g
Lactose 315.00g
Silica gel micropowder 37.50g
Microcrystalline cellulose 780.00g
Low-substituted hydroxypropylcellulose 217.50g
60.00g of crospovidone
Magnesium stearate 15.00 g.
Referring to the technical scheme of the specification example 4 in CN105769872A, the preparation method of the mosapride citrate tablet comprises the following steps:
adding mosapride citrate and aerosil into a grinder with the rotating speed of 3000r/min according to the formula, mixing and grinding for 20s to obtain a composition, mixing the prepared composition with lactose, adding microcrystalline cellulose, low-substituted hydroxypropyl cellulose and crospovidone, uniformly mixing, sieving with a 40-mesh sieve for dispersing for 1 time, adding magnesium stearate, mixing uniformly, and tabletting to obtain the compound.
Dissolution test
The dissolution rates of mosapride citrate in a medium having a pH of 6.8 of samples 1 (example 1), 2 (example 2), 3 (comparative example 1) and a reference formulation (mosapride tablets manufactured by sumitomo pharmaceutical co., ltd. japan) are shown in tables 1, 2, 3 and 4.
Table 1 dissolution profile table of example 1
Table 2 dissolution profile table of example 2
Table 3 dissolution profile of reference formulation
Table 4 dissolution profile of comparative example 1
The dissolution profiles at ph6.8 for the final products of the above two examples are shown in figure 1. As can be seen from tables 1, 2, 3, 4 and fig. 1, the mosapride citrate tablet of the present application starts to be rapidly dissolved after 10min, and the dissolution rate rapidly reaches more than 60%, and the dissolution rate of the comparative example is also close to 60%; when the citric acid mosapride tablet is dissolved out for 20min, the dissolution amount exceeds 80 percent and meets the requirement of the imported drug registration standard JX20080288, while the dissolution rate of the comparative example is lower than 70 percent; the dissolution time is continuously prolonged, when the dissolution time reaches 30min, the dissolution rate of the mosapride citrate tablet reaches 90 percent and the maximum dissolution rate is basically reached, the dissolution rate is basically consistent with that of a reference preparation, particularly, the dissolution performance of the tablet under the condition of the example 1 is even superior to that of the reference preparation used as an imported medicament, and the dissolution rate of the tablet is far lower than that of the imported medicament in cost.
And (3) stability test:
test samples: examples 1 to 2 (samples 1 to 2) were compared with mosapride tablets (referred to as reference preparation) manufactured by Sumitomo pharmaceutical Co., Ltd.
The test method comprises the following steps: respectively standing for six months under the condition of accelerated stability test, measuring the content change by using the mosapride citrate and related substances as indexes, and respectively sampling in 0 th, 1 th, 3 th and 6 th months for detection, and specifically referring to table 5.
TABLE 5 comparison of stability parameters under different implementation conditions
As can be seen from Table 5, after the product was left for 6 months, the reduction rate of the content was 0.5% or less in both example 1 and example 2, and the storage stability of the product was good.
The above description is provided for the purpose of describing the preferred embodiments of the present invention in more detail, and it should not be construed that the embodiments of the present invention are limited to the description above, and it will be apparent to those skilled in the art that the present invention can be implemented in many different forms without departing from the spirit and scope of the present invention.
Claims (2)
1. Mosapride citrate tablets, characterized in that they consist of:
mosapride citrate 26.50g
Lactose 295.00g
160.00g of starch
Low-substituted hydroxypropylcellulose 140.00g
Hydroxypropyl methylcellulose 12.00g
Purified water 188.00g
Magnesium stearate 6.50g
8.25g of micro silica gel powder,
1) weighing the raw materials and the auxiliary materials according to the proportion, and sieving the auxiliary materials with a 60-mesh sieve;
2) weighing purified water, adding hydroxypropyl methylcellulose, stirring for dissolving, and stirring for dissolving to form a hydroxypropyl methylcellulose aqueous solution;
3) transferring lactose, mosapride citrate, starch and the hydroxypropyl methylcellulose water solution formed in the step (2) into a wet granulator in sequence, premixing and performing wet granulation;
4) drying, sieving with 30 mesh sieve, grading, and mixing low-substituted hydroxypropyl cellulose, magnesium stearate and silica gel micropowder;
5) and (6) tabletting.
2. Mosapride citrate tablets, characterized in that they consist of:
mosapride citrate 26.50g
Lactose 300.00g
Starch 150.00g
Low-substituted hydroxypropylcellulose 155.00g
Hydroxypropyl methylcellulose 15.00g
Purified water 188.00g
Magnesium stearate 6.50g
8.00g of micro-powder silica gel,
1) weighing the raw materials and the auxiliary materials according to the proportion, and sieving the auxiliary materials with a 60-mesh sieve;
2) weighing purified water, adding hydroxypropyl methylcellulose, and stirring to dissolve to form a hydroxypropyl methylcellulose water solution;
3) transferring lactose, mosapride citrate, starch and the hydroxypropyl methylcellulose water solution formed in the step (2) into a wet granulator in sequence, premixing and performing wet granulation;
4) drying, sieving with 30 mesh sieve, grading, and mixing low-substituted hydroxypropyl cellulose, magnesium stearate and silica gel micropowder;
5) and (6) tabletting.
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| WO2006011159A2 (en) * | 2004-06-21 | 2006-02-02 | Torrent Pharmaceuticals Limited | Stabilized pharmaceutical composition containing rabeprazole sodium with improved bioavailability |
| CN101273973B (en) * | 2007-03-28 | 2010-04-07 | 成都康弘药业集团股份有限公司 | Dispersible tablet containing mosapride citrate |
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Denomination of invention: Mosapride citrate tablet and its preparation method Effective date of registration: 20230601 Granted publication date: 20200612 Pledgee: Bank of Ningbo Co.,Ltd. Shaoxing Branch Pledgor: ZHEJIANG ANGLIKANG PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980042571 |