CN116036035A - Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet - Google Patents
Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet Download PDFInfo
- Publication number
- CN116036035A CN116036035A CN202310177850.8A CN202310177850A CN116036035A CN 116036035 A CN116036035 A CN 116036035A CN 202310177850 A CN202310177850 A CN 202310177850A CN 116036035 A CN116036035 A CN 116036035A
- Authority
- CN
- China
- Prior art keywords
- tablet
- nuola
- fumaric acid
- raw
- titanium dioxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 title claims abstract description 96
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 239000001530 fumaric acid Substances 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 239000010936 titanium Substances 0.000 title claims abstract description 7
- 229910052719 titanium Inorganic materials 0.000 title claims abstract description 7
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 60
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 29
- 239000008187 granular material Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 24
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 230000008569 process Effects 0.000 claims abstract description 18
- 238000003756 stirring Methods 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 239000011230 binding agent Substances 0.000 claims abstract description 12
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims description 25
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 23
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 23
- 238000000576 coating method Methods 0.000 claims description 23
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 23
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 23
- 239000011248 coating agent Substances 0.000 claims description 21
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 19
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 19
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 19
- 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 18
- 229930195725 Mannitol Natural products 0.000 claims description 18
- 239000000594 mannitol Substances 0.000 claims description 18
- 235000010355 mannitol Nutrition 0.000 claims description 18
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 15
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 15
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 15
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 15
- 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 claims description 12
- 239000000463 material Substances 0.000 claims description 9
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- 229920003081 Povidone K 30 Polymers 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 238000012546 transfer Methods 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 239000004568 cement Substances 0.000 claims description 3
- 238000007906 compression Methods 0.000 claims description 3
- 230000006835 compression Effects 0.000 claims description 3
- 229960000913 crospovidone Drugs 0.000 claims description 3
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 3
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
- 229940032147 starch Drugs 0.000 claims description 3
- 238000005469 granulation Methods 0.000 claims description 2
- 230000003179 granulation Effects 0.000 claims description 2
- 239000003605 opacifier Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 7
- 230000000711 cancerogenic effect Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 6
- 238000005550 wet granulation Methods 0.000 abstract description 5
- 238000009477 fluid bed granulation Methods 0.000 abstract description 4
- 231100000315 carcinogenic Toxicity 0.000 abstract description 3
- 235000010215 titanium dioxide Nutrition 0.000 description 22
- 239000000203 mixture Substances 0.000 description 17
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 229960001855 mannitol Drugs 0.000 description 16
- 229940050411 fumarate Drugs 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 238000004806 packaging method and process Methods 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 239000000853 adhesive Substances 0.000 description 7
- 230000001070 adhesive effect Effects 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000007888 film coating Substances 0.000 description 4
- 238000009501 film coating Methods 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 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 description 4
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 4
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 3
- 231100000357 carcinogen Toxicity 0.000 description 3
- 239000003183 carcinogenic agent Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- 239000000516 sunscreening agent Substances 0.000 description 3
- 229910000004 White lead Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000012463 white pigment Substances 0.000 description 2
- 239000011787 zinc oxide Substances 0.000 description 2
- 235000014692 zinc oxide Nutrition 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical group Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
Images
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
- A61K31/435—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
-
- 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
- A61K9/2813—Inorganic compounds
-
- 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
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- 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)
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of preparation of voronoi fumarate tablets, and discloses a preparation method of a Fu Nuola raw fumarate tablet without titanium dioxide. The preparation method of the titanium dioxide-free fumaric acid Fu Nuola raw tablet comprises the steps of mixing fumaric acid voronoi, a filler, a disintegrating agent, a binder and water, stirring the fumaric acid Fu Nuola raw tablet, the filler, the disintegrating agent and the binder by using a stirring shaft in the mixing process for 5 min, standing for about 2min, continuously stirring, circulating, and granulating in a wet granulator after stirring is finished to obtain fumaric acid Fu Nuola raw granules. According to the preparation method of the fumaric acid Fu Nuola raw tablet without titanium dioxide, the sample prepared by adopting the wet granulation process and the sample prepared by adopting the fluid bed granulation process have the capability of quick dissolution, and meanwhile, the prepared fumaric acid Fu Nuola raw tablet does not contain cancerogenic substances, so that the problem of huge potential safety hazards caused by patients after eating the tablet is solved, and the safety is high.
Description
Technical Field
The invention relates to the technical field of preparation of voronoi fumarate tablets, in particular to a preparation method of a Fu Nuola raw fumarate tablet without titanium dioxide.
Background
Titanium dioxide, an inorganic compound, has no toxicity, optimal opacity, optimal whiteness and brightness, is considered to be the best performing white pigment in the world today. The titanium white has strong adhesion, is not easy to generate chemical change and is always snowy white. Meanwhile, titanium dioxide has a good ultraviolet masking effect, is often used as a sun-screening agent to be mixed into textile fibers, the sun-screening agent is added into coating powder, and superfine titanium dioxide powder is also added into sun cream to prepare sun-screening cosmetics. Titanium dioxide may be obtained from the acid decomposition extraction of rutile or from the decomposition of titanium tetrachloride. Titanium dioxide is stable in nature and is used in large quantities as a white pigment in paints, has good hiding power, is similar to white lead, but does not turn black like white lead; it also has zinc white durability. Titanium dioxide is used as a coating agent, a coloring agent and an ultraviolet ray diluent in pharmaceutical preparations for preparing coated tablets, pills, granules, capsules and external preparations. In lakes, it is used as a masking agent to make the color uniform. Titanium dioxide is used in large amounts in coating powders for pharmaceutical preparations because of its special properties.
At present, the carcinogen list published by the international cancer research institute of the world health organization is primarily arranged and referenced, and titanium dioxide is in the 2B type carcinogen list, so that the Fu Nuola raw fumaric acid tablet prepared by continuously using titanium dioxide as a raw material contains carcinogen substances, and brings great potential safety hazard to patients.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of a fumaric acid Fu Nuola raw tablet without titanium dioxide, which has the advantages of high safety and the like and solves the problem of bringing great potential safety hazard to patients.
In order to achieve the purpose of high safety, the invention provides the following technical scheme: the preparation method of the titanium dioxide-free raw fumaric acid Fu Nuola tablet is characterized by comprising the following raw materials in parts by weight: ten parts of raw materials are total, wherein, talcum powder is eight parts, mannitol is one part, and povidone K30 is one part.
Preferably, the talcum powder accounts for eighty percent of the total raw materials, and the calcium carbonate can replace talcum powder as a component of the titanium dioxide serving as an opacifier.
The invention aims to provide a preparation method of a raw fumaric acid Fu Nuola tablet without titanium dioxide, which is characterized by comprising the following steps:
s1, granulating raw materials
The fumaric acid Fu Nuola raw material, the filler, the disintegrating agent, the binder and the water provided by the invention are mixed, and in the mixing process, the fumaric acid Fu Nuola raw material, the filler, the disintegrating agent and the binder are stirred by using a stirring shaft for 5 min, and after standing for about 2min, the mixture is continuously stirred, so that the mixture circulates, and after the stirring is finished, the mixture is made into wet granules in a wet granulator, so as to obtain fumaric acid Fu Nuola raw granules.
S2, tabletting process
The tablet press is arranged on a firm wooden workbench (also can be arranged on a cement table) and is fixed by three pairs of M12 anchor screws, so that the stability of the tablet press is ensured, and then the mixed raw materials are placed in the tablet press for realizing the purpose of tabletting tablets.
S3, coating process
According to the characteristics and the specification of the tablet, the tablet is coated, when the tablet is coated, after the tablet core is pressed by one tablet press, the tablet core is transferred into a die hole of the other tablet press by a transfer device, fine powder outside the tablet is removed by a suction pump in the transfer process, before the tablet core reaches a second tablet press, part of coating material is filled into the die hole as a bottom layer, then the tablet core is placed on the die hole, and then the coating material is added to fill the die hole, and the coated tablet is formed by the second compression.
Preferably, in the step S1, the water is used in an amount of 10% -20% based on the total weight of the obtained Fu Nuola raw fumaric acid granules, and the granules are granulated to obtain granules with 20 meshes (0.9 mm pore size sieve) and a bulk density of 0.5-0.7g/ml and a compactibility of 0.6-0.8g/ml.
Preferably, in the step S1, the filler, the disintegrant and the binder are selected from one or more of the following: mannitol, microcrystalline cellulose, pregelatinized starch, crospovidone, croscarmellose sodium, povidone K30, hydroxypropyl cellulose and starch.
Preferably, in the step S2, the tablet thickness may be adjusted by itself, and the thin tablet thickness may be produced.
Preferably, in the step S3, the temperature should be controlled at 5-15 ℃ in the process of coating the tablets.
Compared with the prior art, the invention provides a preparation method of a fumaric acid Fu Nuola raw tablet without titanium dioxide, which has the following beneficial effects:
1. according to the preparation method of the fumaric acid Fu Nuola raw tablet without titanium dioxide, the sample prepared by adopting the wet granulation process and the sample prepared by adopting the fluid bed granulation process have the capability of quick dissolution, and meanwhile, the prepared fumaric acid Fu Nuola raw tablet does not contain cancerogenic substances, so that the problem of huge potential safety hazards caused by patients after eating the tablet is solved, and the safety is high.
Drawings
FIG. 1 is a flow chart of a method of producing a medicament according to the present invention;
FIG. 2 is a graph of data from the detection of bare sample placement under intense light;
FIG. 3 shows a test chart under a dissolution medium with the same dissolution profile test method.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The preparation method of the titanium dioxide-free raw fumaric acid Fu Nuola tablet is characterized by comprising the following raw materials in parts by weight: the raw materials are ten parts in total, wherein the talcum powder comprises eight parts, one part of mannitol and one part of povidone K30, the talcum powder accounts for eighty percent of the total raw materials, and the calcium carbonate can replace the talcum powder as a component of the titanium dioxide serving as a light screening agent.
The invention aims to provide a preparation method of a raw fumaric acid Fu Nuola tablet without titanium dioxide, which is characterized by comprising the following steps:
s1, granulating raw materials
The fumaric acid Fu Nuola raw material, the filler, the disintegrating agent, the binder and the water provided by the invention are mixed, and in the mixing process, the fumaric acid Fu Nuola raw material, the filler, the disintegrating agent and the binder are stirred by using a stirring shaft for 5 min, and after standing for about 2min, the mixture is continuously stirred, so that the mixture circulates, and after the stirring is finished, the mixture is made into wet granules in a wet granulator, so as to obtain fumaric acid Fu Nuola raw granules.
S2, tabletting;
the tablet press is arranged on a firm wooden workbench (also can be arranged on a cement table) and is fixed by three pairs of M12 anchor screws, so that the stability of the tablet press is ensured, and then the mixed raw materials are placed in the tablet press for realizing the purpose of tabletting tablets.
S3, coating process
According to the characteristics and the specification of the tablet, the tablet is coated, when the tablet is coated, after the tablet core is pressed by one tablet press, the tablet core is transferred into a die hole of the other tablet press by a transfer device, fine powder outside the tablet is removed by a suction pump in the transfer process, before the tablet core reaches a second tablet press, part of coating material is filled into the die hole as a bottom layer, then the tablet core is placed on the die hole, and then the coating material is added to fill the die hole, and the coated tablet is formed by the second compression.
The total weight of the obtained Fu Nuola raw fumaric acid granules is 10-20%, the granules are 20 meshes (0.9 mm aperture sieve), the bulk density is 0.5-0.7g/ml, the compactness is 0.6-0.8g/ml, and the filler, the disintegrating agent and the binder are selected from one or more of the following: mannitol, microcrystalline cellulose, pregelatinized starch, crospovidone, croscarmellose sodium, povidone K30, hydroxypropyl cellulose and starch, the tablet thickness can be adjusted by itself, the tablet thickness can be produced, and the temperature should be controlled at 5-15 ℃ in the process of coating the tablet.
Example 1 prescription:
fu Nuola raw fumaric acid 13 parts by weight
Mannitol 70 parts by weight
10 parts by weight of microcrystalline cellulose (pH 101)
2 parts by weight of croscarmellose sodium
Hydroxypropyl cellulose 2 weight portions
Purified water 20 parts by weight
2 parts by weight of croscarmellose sodium
1 part by weight of magnesium stearate
Film coating aqueous solution composition 4 parts by weight
Hydroxypropyl methylcellulose
Red iron oxide
Polyethylene glycol 6000
Talc powder
The preparation method comprises the following steps:
(1) Adhesive solution formulation
Weighing a prescription amount of hydroxypropyl cellulose, and dissolving the hydroxypropyl cellulose with purified water to obtain an aqueous solution of the hydroxypropyl cellulose;
(2) Granulating
Weighing the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium according to a prescription, putting the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium into a wet granulator together, and uniformly mixing; pouring the adhesive solution obtained in the step (1) into the uniformly mixed raw materials and auxiliary materials to prepare a soft material, stirring and granulating;
(3) Drying and granulating
Drying the prepared granules, and sieving and granulating the dried granules;
(4) General mixing
Uniformly mixing the finished dry particles with the prescribed amount of croscarmellose sodium and magnesium stearate;
(5) Tabletting, coating and packaging
Tabletting, coating and packaging the mixed granules.
Example 2 prescription:
fu Nuola raw fumaric acid 13 parts by weight
Mannitol 70 parts by weight
10 parts by weight of microcrystalline cellulose (pH 101)
2 parts by weight of croscarmellose sodium
Hydroxypropyl cellulose 2 weight portions
Purified water 20 parts by weight
2 parts by weight of croscarmellose sodium
1 part by weight of magnesium stearate
Film coating aqueous solution composition 4 parts by weight
Hydroxypropyl methylcellulose
Red iron oxide
Polyethylene glycol 6000
Zinc oxide
The preparation method comprises the following steps:
(1) Adhesive solution formulation
Weighing a prescription amount of hydroxypropyl cellulose, and dissolving the hydroxypropyl cellulose with purified water to obtain an aqueous solution of the hydroxypropyl cellulose;
(2) Granulating
Weighing the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium according to a prescription, putting the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium into a wet granulator together, and uniformly mixing; pouring the adhesive solution obtained in the step (1) into the uniformly mixed raw materials and auxiliary materials to prepare a soft material, stirring and granulating;
(3) Drying and granulating
Drying the prepared granules, and sieving and granulating the dried granules;
(4) General mixing
Uniformly mixing the finished dry particles with the prescribed amount of croscarmellose sodium and magnesium stearate;
(5) Tabletting, coating and packaging
Tabletting, coating and packaging the mixed granules.
Example 3 prescription:
fu Nuola raw fumaric acid 13 parts by weight
Mannitol 70 parts by weight
10 parts by weight of microcrystalline cellulose (pH 101)
2 parts by weight of croscarmellose sodium
Hydroxypropyl cellulose 2 weight portions
Purified water 20 parts by weight
2 parts by weight of croscarmellose sodium
1 part by weight of magnesium stearate
Film coating aqueous solution composition 4 parts by weight
Hydroxypropyl methylcellulose
Red iron oxide
Polyethylene glycol 6000
Titanium dioxide
The preparation method comprises the following steps:
(1) Adhesive solution formulation
Weighing a prescription amount of hydroxypropyl cellulose, and dissolving the hydroxypropyl cellulose with purified water to obtain an aqueous solution of the hydroxypropyl cellulose;
(2) Granulating
Weighing the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium according to a prescription, putting the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium into a wet granulator together, and uniformly mixing; pouring the adhesive solution obtained in the step (1) into the uniformly mixed raw materials and auxiliary materials to prepare a soft material, stirring and granulating;
(3) Drying and granulating
Drying the prepared granules, and sieving and granulating the dried granules;
(4) General mixing
Uniformly mixing the finished dry particles with the prescribed amount of croscarmellose sodium and magnesium stearate;
(5) Tabletting, coating and packaging
Tabletting, coating and packaging the mixed granules.
Example 4, recipe:
fu Nuola raw fumaric acid 13 parts by weight
Mannitol 70 parts by weight
10 parts by weight of microcrystalline cellulose (pH 101)
2 parts by weight of croscarmellose sodium
Hydroxypropyl cellulose 2 weight portions
Purified water 20 parts by weight
2 parts by weight of croscarmellose sodium
1 part by weight of magnesium stearate
Film coating aqueous solution composition 4 parts by weight
Hydroxypropyl methylcellulose
Red iron oxide
Polyethylene glycol 6000
Stearic acid
The preparation method comprises the following steps:
(1) Adhesive solution formulation
Weighing a prescription amount of hydroxypropyl cellulose, and dissolving the hydroxypropyl cellulose with purified water to obtain an aqueous solution of the hydroxypropyl cellulose;
(2) Granulating
And weighing the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium according to a prescription, putting the voronoi fumarate, mannitol, microcrystalline cellulose and croscarmellose sodium into a fluidized bed granulating and coating machine together, and preheating and mixing the mixture. Granulating the mixture while spraying the binder solution of step (1) to obtain granulated dry particles.
(3) Finishing grain
Sieving the prepared dry granules and granulating;
(4) General mixing
Uniformly mixing the finished dry particles with the prescribed amount of croscarmellose sodium and magnesium stearate;
(5) Tabletting, coating and packaging
Tabletting, coating and packaging the mixed granules.
The inventor finds through experiments that after titanium dioxide belonging to the class 2B cancerogenic substances is replaced by talcum powder, fumaric acid Fu Nuola is still stable under the illumination condition. And compared with the fluidized bed granulation process, the voronoi green sheet fumarate prepared by the wet granulation process can achieve the effect of quick dissolution.
The following describes the formulation of examples 1-3 of the present invention as a stable property under light conditions of the product after talc is substituted for titanium dioxide.
The experiment was set up according to the principle of single factor control, and the samples of examples 1-3 were exposed to intense light for 10 days for content and related substance detection, and the experimental data of the test are shown in the following table.
From the data of fig. 2, the following conclusions can be drawn:
under the same test conditions, talcum powder can be used for replacing titanium dioxide as a light shielding agent to keep the stability of the Vonopraz fumarate tablet under the illumination condition.
The wet granulation process preparation samples were given as examples 3, 4 of the invention, which showed equivalent fast dissolution properties as the fluid bed granulation process.
The experiment is set according to a single factor control principle, samples of the embodiment 3 and the embodiment 4 are detected by adopting the same dissolution curve detection method and the same dissolution medium, and specific experimental data are shown in figure 3.
From the data of fig. 3, the following conclusions can be drawn:
(1) Under the same test conditions, the samples prepared by the wet granulation process and the samples prepared by the fluid bed granulation process have the capability of quick dissolution.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (7)
1. The preparation method of the titanium dioxide-free raw fumaric acid Fu Nuola tablet is characterized by comprising the following raw materials in parts by weight: ten parts of raw materials are total, wherein, talcum powder is eight parts, mannitol is one part, and povidone K30 is one part.
2. The method for preparing a raw fumaric acid Fu Nuola tablet without titanium dioxide according to claim 1, wherein the talcum powder accounts for eighty percent of the total raw materials, and the calcium carbonate can be used as an ingredient of the titanium dioxide serving as an opacifier instead of talcum powder.
3. A method of preparing a titanium dioxide-free raw fumaric acid tablet Fu Nuola according to claim 1 comprising the steps of:
s1, granulating raw materials
Mixing the fumaric acid Fu Nuola raw material, the filler, the disintegrating agent, the binder and the water, stirring the fumaric acid Fu Nuola raw material, the filler, the disintegrating agent and the binder by using a stirring shaft in the mixing process for 5 min, standing for about 2min, continuing stirring, circulating, and preparing wet granules in a wet granulator after stirring to obtain fumaric acid Fu Nuola raw granules;
s2, tabletting process
The tablet press is arranged on a firm wooden workbench (also can be arranged on a cement table) and is fixed by three pairs of M12 anchor screws, so that the stability of the tablet press is ensured, and then the mixed raw materials are placed into the tablet press for realizing the purpose of tabletting tablets;
s3, coating process
According to the characteristics and the specification of the tablet, the tablet is coated, when the tablet is coated, after the tablet core is pressed by one tablet press, the tablet core is transferred into a die hole of the other tablet press by a transfer device, fine powder outside the tablet is removed by a suction pump in the transfer process, before the tablet core reaches a second tablet press, part of coating material is filled into the die hole as a bottom layer, then the tablet core is placed on the die hole, and then the coating material is added to fill the die hole, and the coated tablet is formed by the second compression.
4. The process for producing a raw fumaric acid Fu Nuola tablet free of titanium dioxide according to claim 1, wherein in the step S1, the amount of water is 10% -20% based on the total weight of the obtained Fu Nuola raw fumaric acid granules, and the granulation is such that the obtained granules are 20 mesh (0.9 mm pore size sieve), bulk density is 0.5-0.7g/ml and compactability is 0.6-0.8g/ml.
5. The method for preparing a raw fumaric acid Fu Nuola tablet without titanium dioxide according to claim 1, wherein in the step S1, the filler, the disintegrating agent and the binder are selected from one or more of the following: mannitol, microcrystalline cellulose, pregelatinized starch, crospovidone, croscarmellose sodium, povidone K30, hydroxypropyl cellulose and starch.
6. The method for preparing a raw fumaric acid Fu Nuola tablet without titanium dioxide according to claim 1, wherein in the step S2, the tablet thickness can be adjusted by itself, and the thick slices can be produced.
7. The method for preparing a raw fumaric acid Fu Nuola tablet without titanium dioxide according to claim 1, wherein in the step S3, the temperature is controlled to be 5-15 ℃ in the process of coating the tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310177850.8A CN116036035A (en) | 2023-02-28 | 2023-02-28 | Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310177850.8A CN116036035A (en) | 2023-02-28 | 2023-02-28 | Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116036035A true CN116036035A (en) | 2023-05-02 |
Family
ID=86123857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310177850.8A Pending CN116036035A (en) | 2023-02-28 | 2023-02-28 | Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116036035A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117462507A (en) * | 2023-12-28 | 2024-01-30 | 山东齐都药业有限公司 | Vonola fumarate crude drug composition and preparation method thereof |
-
2023
- 2023-02-28 CN CN202310177850.8A patent/CN116036035A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117462507A (en) * | 2023-12-28 | 2024-01-30 | 山东齐都药业有限公司 | Vonola fumarate crude drug composition and preparation method thereof |
| CN117462507B (en) * | 2023-12-28 | 2024-03-15 | 山东齐都药业有限公司 | Vonola fumarate crude drug composition and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104523641B (en) | Lansoprazole intestine preparation and preparation method thereof | |
| CN101932241A (en) | Pharmaceutical compositions of a combination of metformin and a dipeptidyl peptidase-iv inhibitor | |
| BG60501B1 (en) | Cholesteramine tablet and method for its preparation | |
| CN116036035A (en) | Preparation method of titanium dioxide-free raw fumaric acid Fu Nuola tablet | |
| JPS6121526B2 (en) | ||
| CN103599085B (en) | A kind of Aspirin Enteric-coated Tablets and preparation technology thereof | |
| CN105147614B (en) | A kind of solid pharmaceutical preparation and preparation method thereof including BIBW 2992MA2 | |
| CN104983732B (en) | A kind of cloth Lip river feritin that quick and preparation method thereof | |
| CN109157522A (en) | Pharmaceutical composition and its preparation method and application comprising Xi Gelieting or its officinal salt | |
| KR20010051514A (en) | Low-Substituted Hydroxypropylcelluloses and Process for the Preparation thereof | |
| CN109925290A (en) | Theo-Dur and its preparation process | |
| CN107115312A (en) | A kind of Noroxin and preparation method thereof | |
| CN107998097B (en) | A kind of tablet and preparation method thereof containing olmesartan medoxomil | |
| CN105853384A (en) | Azilsartan tablets and preparation method thereof | |
| CA2265211A1 (en) | Making dosage units using low shear granulation | |
| CN108567759A (en) | A kind of valsartan and Hydrochlorothiade piece and preparation method thereof | |
| WO1997039752A1 (en) | Sertindole preparation and process for the production thereof | |
| WO2006057194A1 (en) | Solid agent and process for producing the same | |
| CN108686222A (en) | The preparation method of Rosuvastatin calcium composition | |
| CN102525992A (en) | L-alpha-glycerophosphoryl choline film-coated tablet and preparation method thereof | |
| CN110051639B (en) | Rapidly disintegrating nicergoline tablet and preparation method thereof | |
| CN109875969B (en) | Stable ivabradine hydrochloride tablet and preparation method thereof | |
| CN105596341B (en) | A kind of amber love song Ge Lieting solid pharmaceutical preparations and preparation method | |
| CN112641750A (en) | Paroxetine hydrochloride tablet and preparation method thereof | |
| US3148123A (en) | Granulating and coating tablets |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |