CN106214657B - Thin membrane coated tablet of mosapride citrate and preparation method thereof - Google Patents
Thin membrane coated tablet of mosapride citrate and preparation method thereof Download PDFInfo
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- CN106214657B CN106214657B CN201610807005.4A CN201610807005A CN106214657B CN 106214657 B CN106214657 B CN 106214657B CN 201610807005 A CN201610807005 A CN 201610807005A CN 106214657 B CN106214657 B CN 106214657B
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- mosapride citrate
- composition
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- film coating
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- 229960004085 mosapride Drugs 0.000 title claims abstract description 40
- 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 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000012528 membrane Substances 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000007888 film coating Substances 0.000 claims description 33
- 238000009501 film coating Methods 0.000 claims description 33
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 14
- 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 description 13
- 239000008101 lactose Substances 0.000 claims description 13
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 10
- 239000000377 silicon dioxide Substances 0.000 claims description 10
- 238000005507 spraying Methods 0.000 claims description 10
- 238000005550 wet granulation Methods 0.000 claims description 10
- 235000020985 whole grains Nutrition 0.000 claims description 10
- 239000003643 water by type Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 239000007941 film coated tablet Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- -1 hydroxypropyl Chemical class 0.000 claims description 6
- 239000010410 layer Substances 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 239000012792 core layer Substances 0.000 claims description 2
- 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 description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 239000008213 purified water Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 abstract description 8
- 239000011248 coating agent Substances 0.000 abstract description 6
- 238000005286 illumination Methods 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 2
- 238000005260 corrosion Methods 0.000 abstract 1
- 230000007797 corrosion Effects 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 25
- 239000000243 solution Substances 0.000 description 17
- 239000004014 plasticizer Substances 0.000 description 12
- 229920002472 Starch Polymers 0.000 description 11
- 239000008107 starch Substances 0.000 description 11
- 235000019698 starch Nutrition 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 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
- 230000000052 comparative effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000006549 dyspepsia Diseases 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 210000004994 reproductive system Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 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 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010051153 Diabetic gastroparesis Diseases 0.000 description 1
- 206010059186 Early satiety Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- IWWJTUVMNORSNK-UHFFFAOYSA-N O.O.NC(=O)C1=CC=CC=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O Chemical compound O.O.NC(=O)C1=CC=CC=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O IWWJTUVMNORSNK-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 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 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical class C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000005985 stomach dysfunction Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical class [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2022—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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of pharmaceutical composition containing active component mosapride citrate and preparation method thereof method.Specifically, the pharmaceutical composition of mosapride citrate prepared by the present invention can meet that coating requires, improve dissolved corrosion of the mosapride citrate pharmaceutical composition in different medium, and improve stability of the said composition in illumination period.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to contains mosapride citrate pharmaceutical composition and its preparation side
Method.
Background technology
Mosapride citrate (formula 1), chemical name (±) -4- amino -5- chloro-2-ethoxies-N- [[4- (4- fluorine benzyls
Base) -2- morpholinyls] methyl] benzamide dihydrate citrate is the (5-HT of selective serotonin 44) receptor agonism
Agent, pass through excited intestines and stomach cholinergic intrerneuron and the 5-HT of myenteric nerve plexus4Acceptor, promote the release of acetylcholine,
So as to strengthen gastrointestinal movement, improve the gastrointestinal symptom of functional dyspepsia FD patient, and do not influence the secretion of hydrochloric acid in gastric juice.It is clinical
For functional dyspepsia FD with symptoms of digestive tract such as heartburn, belch, Nausea and vomiting, early satiety, big bellies；It can also be used for
The stomach dysfunction of GORD, diabetic gastroparesis and part pacing stomach patient.
USP patents NO.4870074 is disclosed containing mosapride citrate, cornstarch, lactose, microcrystalline cellulose, hydroxyl
The composition of propyl cellulose, light anhydrous silicic acid acid anhydride and magnesium stearate.Additionally due to Mosapride taste is more bitter, it need to be carried out
Coating.
Chinese patent CN101405004A has found that in general thin coated tablet plasticizer is recognized when forming clad
To be required, and it also found and utilize the film coating composition for including these certain plasticizers for promoting Mosapride to decompose
When manufacturing film coating tablet, the decomposition of Mosapride is promoted.
But plasticizer is a kind of high polymer material, species is various, including the phenolphthalein esters in environmental estrogens.It is domestic
Outer many zooperies all show that these plasticizer have harm to organism.The molecular structure of some plasticizer is similar to He Er
Cover, long-term use has reproductive system risk, if dibutyl phthalate is to the toxic effect of human reproductive system, particularly pair
In male.
Plasticizer is must be added to change the physical-mechanical properties of macromolecule membrane in general coated formula, makes it more soft
Property, it is easy to film forming.Usually as the increased means of catabolite are suppressed, take more and remove plasticizer from film coating component, so
And this will cause to reduce productivity ratio during film coating, and influence the FINAL APPEARANCE of film-coated tablet.
Therefore, one kind is badly in need of in the case where being added without plasticizer in this area, can be under illumination period and hot conditions
The stability of medicine activity component is kept, while meets that coating requires and has the Pharmaceutical composition of excellent dissolution rate.
The content of the invention
It is an object of the invention to solve the above problems, there is provided the mosapride citrate medicine group shown in a kind of formula (I)
Compound
It is characterized in that：
(a) piece sandwich layer shown in formula (1) is contained, described sandwich layer is free of adhesive；
(b) piece core layer surface contains based calcium, the coatings not plasticizer-containing, and at least contain hypromellose
Element；With one kind in polyvinyl alcohol, hydroxypropyl cellulose, glycerin monostearate.
Preferably, described sandwich layer includes 1-10mg mosapride citrates, preferably 5mg.
Preferably, described pharmaceutical composition piece sandwich layer contains diluent, disintegrant and lubricant.
Preferably, one kind in lactose, starch, mannitol, lactose starch or mannitol starch of the diluent or
It is several.
Preferably, the disintegrant is selected from low-substituted hydroxypropyl cellulose, Ac-Di-Sol, CMS
One or more in sodium and PVPP.
Preferably, one or more of the lubricant in magnesium stearate, silica and talcum powder.
Preferably, the opacifier is selected from titanium dioxide or titanium oxide.
Preferably, a kind of composition containing mosapride citrate provided by the invention, in composition each component and its
Percentage by weight is as follows：
Label forms：
Film coating composition：
Preferably, each component and percentage by weight are as follows in its composition：
Film coating composition：
Preferably, a kind of composition containing mosapride citrate provided by the invention, in composition each component and its
Percentage by weight is as follows：
Label forms：
Film coating composition：
Preferably, each component and percentage by weight are as follows in its composition：
Film coating composition：
Preferably, a kind of composition containing mosapride citrate provided by the invention, in composition each component and its
Percentage by weight is as follows：
Label forms：
Film coating composition：
Preferably, each component and percentage by weight are as follows in its composition：
Label forms：
Film coating composition：
Preferably, a kind of composition containing mosapride citrate provided by the invention, in composition each component and its
Percentage by weight is as follows：
Label forms：
Film coating composition：
Preferably, each component and percentage by weight are as follows in its composition：
Label forms：
Film coating composition：
In addition, the present invention provides the preparation method of above-mentioned composition, comprise the following steps：
(1) by diluent, interior plus disintegrant and mosapride citrate wet granulation, dry, sieving whole grain；
(2) additional disintegrant and lubricant is optionally added into always to mix；
(3) gained particle is compressed to label using punch die；
(4) by the core tablet of above-mentioned acquisition, with film coating solution spraying, film-coated tablet is obtained.
Preferably, water or ethanol water are added in the step (1) as wetting agent.
Preferably, film coating composition is dissolved in water, ethanol or its in the mixed solvent to prepare film coating solution.
Pharmaceutical composition used in the present invention has superiority in terms of storage stability, especially under illumination and high temperature
Have good stability.
In addition, applicant has surprisingly found that, the Mosapride pharmaceutical composition of not plasticizer-containing of the invention by using
One or more of mixing in polyvinyl alcohol, hydroxypropyl cellulose, glycerin monostearate or Tween-80 are used as coating material,
Satisfaction can be coated and require that finished appearance is good in the case of not plasticizer-containing.
In addition, applicant has surprisingly found that, when piece sandwich layer does not contain adhesive, and polyvinyl alcohol, hydroxyl are added in coatings
Propyl cellulose, glycerin monostearate or Tween-80, the drug regimen photostability containing Mosapride is more preferable, and medicine
Compositions dissolution is more excellent.
Embodiment
Below in conjunction with specific embodiment, embodiment of the present invention is described in detail.Example below is only used for
Illustrate the present invention, and should not be taken as limiting the scope of the invention.
Comparative example 1 (sample 1)
[table 1] label forms
The composition of [table 2] film coating aqueous solution
Proportion of composing as shown in upper table [1] prepares the plain piece (core tablet) for including mosapride citrate.
Hydroxypropyl cellulose 10g is dissolved in 40g purified waters, obtains binder solution.The binder solution of preparation is added
To containing mosapride citrate (5.29g), lactose (51.91g), starch (32.4g) and low-substituted hydroxypropyl cellulose
Wet granulation in (9.5g) homomixture, 30 mesh sieve whole grains are crossed after drying and by low-substituted hydroxypropyl cellulose (9g), magnesium stearate
(1.3g) and silica (0.6g) are always mixed.Then by gained particle with diameter 6.5mm rush film carry out suppress hardness be
3-10kg plain piece.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [2], film is obtained
Coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Comparative example 2 (sample 2)
[table 3] label forms
The composition of [table 4] film coating aqueous solution
Proportion of composing as shown in upper table [3] prepares the plain piece (core tablet) for including mosapride citrate.
By 40g purified waters be added to containing mosapride citrate (5.29g), lactose (61.91g), starch (32.4g) and
Wet granulation in low-substituted hydroxypropyl cellulose (9.5g) homomixture, 30 mesh sieve whole grains and low substituted hydroxy-propyl is fine are crossed after drying
Dimension plain (9g), magnesium stearate (1.3g) and silica (0.6g) are always mixed.Then rushing gained particle diameter 6.5mm
Film carries out suppressing the plain piece that hardness is 3-10kg.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [4], film is obtained
Coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Comparative example 3 (sample 3)
[table 5] label forms
The composition of [table 6] film coating aqueous solution
Proportion of composing as shown in upper table [5] prepares the plain piece (core tablet) for including mosapride citrate.
Hydroxypropyl cellulose 10g is dissolved in 40g purified waters, obtains binder solution.The binder solution of preparation is added
To containing mosapride citrate (5.29g), lactose (51.91g), starch (32.4g) and low-substituted hydroxypropyl cellulose
Wet granulation in (9.5g) homomixture, 30 mesh sieve whole grains are crossed after drying and by low-substituted hydroxypropyl cellulose (9g), magnesium stearate
(1.3g) and silica (0.6g) are always mixed.Then by gained particle with diameter 6.5mm rush film carry out suppress hardness be
3-10kg plain piece.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [6], film is obtained
Coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Embodiment 1 (sample 4)
[table 7] label forms
The composition of [table 8] film coating aqueous solution
Proportion of composing as shown in upper table [7] prepares the plain piece (core tablet) for including mosapride citrate.
By 40g purified waters be added to containing mosapride citrate (5.29g), lactose (61.91g), starch (32.4g) and
Wet granulation in low-substituted hydroxypropyl cellulose (9.5g) homomixture, 30 mesh sieve whole grains and low substituted hydroxy-propyl is fine are crossed after drying
Dimension plain (9g), magnesium stearate (1.3g) and silica (0.6g) are always mixed.Then rushing gained particle diameter 6.5mm
Film carries out suppressing the plain piece that hardness is 3-10kg.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [8], film is obtained
Coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Embodiment 2 (sample 5)
[table 9] label forms
The composition of [table 10] film coating aqueous solution
Proportion of composing as shown in upper table [9] prepares the plain piece (core tablet) for including mosapride citrate.
40g purified waters are added to containing mosapride citrate (5.29g), lactose starch (92.81g) and low substitution hydroxyl
Wet granulation in propyl cellulose (14g) homomixture, dry after cross 30 mesh sieve whole grains and by low-substituted hydroxypropyl cellulose (6g),
Magnesium stearate (1.9g) is always mixed.Then by gained particle with diameter 6.5mm rush film carry out suppress hardness be 3-10kg's
Plain piece.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [10], obtain
Film-coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Embodiment 3 (sample 6)
[table 11] label forms
The composition of [table 12] film coating aqueous solution
Proportion of composing as shown in upper table [11] prepares the plain piece (core tablet) for including mosapride citrate.
40g purified waters are added to containing mosapride citrate (5.29g), lactose (61.91g), mannitol (32.4g)
With wet granulation in low-substituted hydroxypropyl cellulose (9.5g) homomixture, 30 mesh sieve whole grains are crossed after drying and by low substituted hydroxy-propyl
Cellulose (9g), magnesium stearate (1.3g) and silica (0.6g) are always mixed.Then by gained particle with diameter 6.5mm's
Film is rushed to carry out suppressing the plain piece that hardness is 3-10kg.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [12], obtain
Film-coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Embodiment 4 (sample 7)
[table 13] label forms
The composition of [table 14] film coating aqueous solution
Proportion of composing as shown in upper table [13] prepares the plain piece (core tablet) for including mosapride citrate.
By 40g purified waters be added to containing mosapride citrate (5.29g), lactose (61.91g), starch (32.4g) and
Wet granulation in low-substituted hydroxypropyl cellulose (10g) homomixture, 30 mesh sieve whole grains and low substituted hydroxy-propyl is fine are crossed after drying
Dimension plain (8.5g), magnesium stearate (1.3g) and silica (0.6g) are always mixed.Then by gained particle with diameter 6.5mm's
Film is rushed to carry out suppressing the plain piece that hardness is 3-10kg.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [14], obtain
Film-coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Embodiment 5 (sample 8)
[table 15] label forms
The composition of [table 16] film coating aqueous solution
Proportion of composing as shown in upper table [15] prepares the plain piece (core tablet) for including mosapride citrate.
40g purified waters are added to and formed sediment containing mosapride citrate (5.29g), lactose starch (97.81g) and carboxymethyl
Wet granulation in powder sodium (10g) homomixture, 30 mesh sieve whole grains are crossed after drying and by sodium carboxymethyl starch (5g), magnesium stearate
(1.3g) and silica (0.6g) are always mixed.Then by gained particle with diameter 6.5mm rush film carry out suppress hardness be
3-10kg plain piece.
By the plain piece (core tablet) of above-mentioned acquisition, with the film coating solution spraying with composition shown in table [16], obtain
Film-coated tablet (per agreement that contracts a film or TV play to an actor or actress 124g).
Experimental example 1 is coated outward appearance
Pharmaceutical composition of the present invention is can be seen that in not plasticizer-containing and adhesive from coating appearance test, and coating group
Contain hydroxypropyl methylcellulose in point；During with a kind of in polyvinyl alcohol, hydroxypropyl cellulose, glycerin monostearate, outside finished product
See well, no loose pieces, sliver phenomenon, meet formulation requirements.
The study on the stability of experimental example 2 is tested
The film-coated tablet of acquisition is placed in transparent vial, it is tightly sealed, 1 or 6 months are preserved at 40 DEG C,
Preserved 10 or 30 days under illumination (4500lux ± 500lux).
Before Sample storage and after preservation, water is used:Methanol=1:9 mixed solvent extraction tablet, is surveyed by HPLC
It is fixed maximum single miscellaneous and total miscellaneous.
HPLC experimental conditions are as follows：
Instrument and reagent：High performance liquid chromatograph, electronic analytical balance, acetonitrile, citric acid, hydrochloric acid, water.
Chromatographic condition：Chromatographic column：C18(5μ150*4.6mm)；Flow velocity is 1.0ml/min；Detection wavelength is 274nm；Column temperature
For 40 DEG C；Sampling volume is 10 μ l.
Mobile phase A：8.82g sodium citrates are taken, are dissolved in 800ml water, pH to 4.0 is adjusted with watery hydrochloric acid, adds water to
1000ml；Mobile phase B：Acetonitrile
According to the form below is eluted (flowing phasor is scalable, ratio can be adjusted suitably)
| Time (min) | 0 | 44 |
| Mobile phase A (%) | 85 | 45 |
| Mobile phase B (%) | 15 | 55 |
The measurement range of peak area is 44 minutes
Table 17：The stability of different samples under illumination condition
Table 18：40 DEG C, the stability of different samples under the conditions of 75%RH
The dissolution test of experimental example 3
With reference to《Chinese Pharmacopoeia 2015 editions》Annex dissolution method, to above-mentioned sample, dissolution rate enters under condition of different pH
Investigation is gone, as a result as shown in table 3,4,5,6.Test result indicates that under each ambient condition, reach in sample 15min
More than 85% dissolution.
Dissolution rate of the table 19 in pH=6.8 phosphate buffer solutions
Dissolution rate of the table 20 in pH=4.0 acetate buffer solution
Dissolution rate of the table 21 in pH=1.2 hydrochloric acid solution
Dissolution rate of the table 22 in the aqueous solution
Claims (1)
1. the mosapride citrate pharmaceutical composition shown in formula (I), it is characterised in that：
It is made up of the based calcium of the piece sandwich layer containing mosapride citrate and piece core layer surface, wherein,
The composition of label is：Mosapride citrate 5.29g, lactose 61.91g, mannitol 32.4g, the interior low-substituted hydroxypropyl added
Base cellulose 9.5g, additional low-substituted hydroxypropyl cellulose 9g, magnesium stearate 1.3g, silica 0.6g, add up to 1000；
The composition of the film coating aqueous solution is：Hydroxypropyl methylcellulose 5.2g, Tween-80 1.4g, titanium dioxide 0.8g and purified water
82.6g；
The preparation method of described pharmaceutical composition is：40g purified waters are added to containing mosapride citrate 5.29g, lactose
Wet granulation in 61.91g, mannitol 32.4g and low-substituted hydroxypropyl cellulose 9.5g homomixtures, 30 mesh sieve whole grains are crossed after drying
And always mixed low-substituted hydroxypropyl cellulose 9g, magnesium stearate 1.3g and silica 0.6g, then gained particle is used
Diameter 6.5mm punch die is pressed into the plain piece that hardness is 3-10kg；The plain piece of above-mentioned acquisition is used to the described film coating aqueous solution
Spraying, obtain film-coated tablet.
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| CN201610807005.4A CN106214657B (en) | 2016-09-06 | 2016-09-06 | Thin membrane coated tablet of mosapride citrate and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021107370A1 (en) * | 2019-11-29 | 2021-06-03 | 한국유나이티드제약 주식회사 | Core tablet preparation comprising proton pump inhibitor and mosapride |
| WO2021118026A1 (en) * | 2019-12-10 | 2021-06-17 | 한국유나이티드제약 주식회사 | Core tablet formulation containing proton pump inhibitor and mosapride |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110354093B (en) * | 2019-07-31 | 2021-09-17 | 常州恒邦药业有限公司 | Mosapride citrate pharmaceutical composition |
| CN116473931B (en) * | 2022-01-13 | 2024-11-26 | 山东新时代药业有限公司 | A kind of mosapride citrate nanocrystalline chip and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1993131A (en) * | 2004-07-28 | 2007-07-04 | 大日本住友制药株式会社 | Film-coated tablet |
| CN101569615A (en) * | 2009-06-01 | 2009-11-04 | 天津博科林药品包装技术有限公司 | Film coating agent used for exudative solid preparation and method for preparing same |
| CN104188927A (en) * | 2014-09-01 | 2014-12-10 | 鲁南制药集团股份有限公司 | Mosapride citrate tablet and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090143343A1 (en) * | 2007-11-13 | 2009-06-04 | Meritage Pharma, Inc. | Compositions for the treatment of inflammation of the gastrointestinal tract |
| EP2604593A1 (en) * | 2011-12-14 | 2013-06-19 | Sandoz AG | Polymorph of Rilpivirine hydrochloride and its use as antiviral |
-
2016
- 2016-09-06 CN CN201610807005.4A patent/CN106214657B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1993131A (en) * | 2004-07-28 | 2007-07-04 | 大日本住友制药株式会社 | Film-coated tablet |
| CN101569615A (en) * | 2009-06-01 | 2009-11-04 | 天津博科林药品包装技术有限公司 | Film coating agent used for exudative solid preparation and method for preparing same |
| CN104188927A (en) * | 2014-09-01 | 2014-12-10 | 鲁南制药集团股份有限公司 | Mosapride citrate tablet and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021107370A1 (en) * | 2019-11-29 | 2021-06-03 | 한국유나이티드제약 주식회사 | Core tablet preparation comprising proton pump inhibitor and mosapride |
| WO2021118026A1 (en) * | 2019-12-10 | 2021-06-17 | 한국유나이티드제약 주식회사 | Core tablet formulation containing proton pump inhibitor and mosapride |
| KR102334699B1 (en) | 2019-12-10 | 2021-12-06 | 한국유나이티드제약 주식회사 | Cored Tablet Comprising Proton Pump Inhibitor and Mosapride |
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| CN106214657A (en) | 2016-12-14 |
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