CN104434957B - A method of preparing magnalium department double-layer tablets - Google Patents
A method of preparing magnalium department double-layer tablets Download PDFInfo
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- CN104434957B CN104434957B CN201410781440.5A CN201410781440A CN104434957B CN 104434957 B CN104434957 B CN 104434957B CN 201410781440 A CN201410781440 A CN 201410781440A CN 104434957 B CN104434957 B CN 104434957B
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- 238000000034 method Methods 0.000 title claims abstract description 30
- 229910001051 Magnalium Inorganic materials 0.000 title claims abstract description 20
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229920002472 Starch Polymers 0.000 claims abstract description 46
- 229960001138 acetylsalicylic acid Drugs 0.000 claims abstract description 46
- 239000008107 starch Substances 0.000 claims abstract description 44
- 235000019698 starch Nutrition 0.000 claims abstract description 44
- 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 abstract description 17
- 235000005979 Citrus limon Nutrition 0.000 claims abstract description 11
- UTUUIUQHGDRVPU-UHFFFAOYSA-K aluminum;2-aminoacetate;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Al+3].NCC([O-])=O UTUUIUQHGDRVPU-UHFFFAOYSA-K 0.000 claims abstract description 11
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims abstract description 11
- 239000001095 magnesium carbonate Substances 0.000 claims abstract description 11
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims abstract description 11
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 10
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 10
- 239000011975 tartaric acid Substances 0.000 claims abstract description 10
- 244000248349 Citrus limon Species 0.000 claims abstract 2
- 239000002002 slurry Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000008213 purified water Substances 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 7
- 239000008188 pellet Substances 0.000 claims description 7
- 238000007664 blowing Methods 0.000 claims description 6
- 238000005469 granulation Methods 0.000 claims description 6
- 230000003179 granulation Effects 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 4
- 239000004411 aluminium Substances 0.000 abstract description 4
- 229910052782 aluminium Inorganic materials 0.000 abstract description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 abstract description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract 1
- 239000001341 hydroxy propyl starch Substances 0.000 abstract 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 abstract 1
- 229940032147 starch Drugs 0.000 abstract 1
- 229960001367 tartaric acid Drugs 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 19
- 230000000052 comparative effect Effects 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 244000131522 Citrus pyriformis Species 0.000 description 9
- 210000002784 stomach Anatomy 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 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 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 238000005550 wet granulation Methods 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 239000007888 film coating Substances 0.000 description 3
- 238000009501 film coating Methods 0.000 description 3
- 235000013312 flour Nutrition 0.000 description 3
- 210000001156 gastric mucosa Anatomy 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000031891 intestinal absorption Effects 0.000 description 2
- 238000003475 lamination Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 235000019890 Amylum Nutrition 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000219000 Populus Species 0.000 description 1
- 229910003978 SiClx Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 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 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000015689 metaplastic ossification Effects 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
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- UJMBCXLDXJUMFB-GLCFPVLVSA-K tartrazine Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-GLCFPVLVSA-K 0.000 description 1
- 235000012756 tartrazine Nutrition 0.000 description 1
- 239000004149 tartrazine Substances 0.000 description 1
- 229960000943 tartrazine Drugs 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of methods for preparing magnalium department double-layer tablets, this method is using aspirin, tartaric acid, low-substituted hydroxypropyl cellulose, starch and talcum powder as first layer, using heavy magnesium carbonate, Dihydroxyaluminium Aminoacetate, starch, lemon yellow and talcum powder as the second layer, it is then pressed into tablet.Aluminium U.S. department's piece surface made from this method is smooth, not stratified, and stability is good.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to a method of prepare magnalium department double-layer tablets.
Background technique
Aspirin has antipyretic, analgesia, anti-inflammatory, inhibition platelet aggregation, the effect that pre- preventing thrombosis generates.Aspirin by
In blocking thromboxane A2 synthesis, gastric mucosa is damaged, causes gastric mucosa slight rotten to the corn and forms ulcer, bleeding, perforation, therefore, clothes
With aspirin ulcer once being formed, it is easy to happen more serious bleeding.Alkaline drug is antiacid and gastric mucosa protectant, is had
Astriction can form protective film in skin surface, promote the healing of ulcer surface, can also neutralize gastric acid, mitigate flatulence etc..
Therefore, Aspirin and alkaline drug composition compound preparation are had into antipyretic, analgesia, anti-inflammatory effect, by low dose of Ah
Taking charge of a woods and alkaline drug composition compound preparation has inhibition platelet aggregation, the effect that pre- preventing thrombosis generates；Meanwhile can also it subtract
Pessimal stimulation of the low aspirin to stomach significantly reduces the incidence of gastrointestinal mucosa erosion and ulcer, can also increase aspirin
Trap.In addition, alkaline drug can make rapid gastric emptying, so that aspirin be made to quickly enter major absorption site~small intestine.
For aspirin to damp and hot unstable, facile hydrolysis generates free salicylic acid, especially with alkaline drug mixing granulation
Tabletting is also easy to produce interaction, influences the stability of drug.Therefore, the compound preparation of usual aspirin and alkaline drug composition
Using pelletizing respectively, double-layer tablets are pressed into, then by double-layer tablets film coating.Conventional method is by aspirin layer using dry
Method granulation, avoids the damp and hot influence to aspirin stability, it is steady to aspirin to can avoid outside moisture by film coating
It qualitatively influences, while preventing layering caused by double-layer tablets water swelling.
CN101632647A discloses a kind of magnalium department double-layer tablets, with aspirin 810g, amylum pregelatinisatum 430g, winestone
Sour 33g, low-substituted hydroxypropyl cellulose 65g, lauryl sodium sulfate 50g are first layer, with Dihydroxyaluminium Aminoacetate 110g, heavy magnesium carbonate
220g, lactose 500g, 10%PVPk30 90% ethanol solution 800ml, lauryl sodium sulfate 15g be the second layer, then with
The packet of hydroxypropyl methyl cellulose 150g, ethyl cellulose 30g, glycerol 50g, 85% ethyl alcohol 3000ml and talcum powder 20g composition
Clothing liquid coated tablet.This method is also that can avoid influence of the outside moisture to aspirin stability using film coating, is prevented
Layering caused by double-layer tablets water swelling.Since aspirin is slightly soluble substance, at the same by be added lauryl sodium sulfate come
Increase the dissolution of aspirin, but after addition lauryl sodium sulfate, aspirin dissolution is accelerated, and a large amount of aspirin are in stomach
Release generates pessimal stimulation and damage to stomach, and damage can also be generated to stomach by taking lauryl sodium sulfate for a long time, and is coated and is increased
The complexity and production cost of preparation process.
CN102961398A discloses a kind of preparation method of aluminium department magnesium sheet: by aspirin 81g, with after β~cyclodextrin encapsulated,
Refrigeration is filtered, dry, adds lactose 23g, sodium carboxymethyl starch 5g, 10% PVP ethanol solution 30g, silica 1 .1g, lemon
1000 aspirin layer particles are made in lemon Huang aluminum lake 0.05g, tartaric acid 0.85g；Dihydroxyaluminium Aminoacetate 11g, heavy magnesium carbonate
22g is refrigerated with after β~cyclodextrin encapsulated, is filtered, dry, adds lactose 60g, 10% 65~85g of PVP ethanol solution, dioxy
1000 buffer layers are made in SiClx 0.98g, tartrazine aluminum lake 0.02g, are pressed into double-layer tablets.This method uses β~cyclodextrin
Aspirin is included, this method obviously makes manufacturing cost increase, and manufacturing process is also complicated, and it is uneconomical, it is also not suitable for industrial metaplasia
It produces.
CN102198147A discloses a kind of preparation method of aluminium department magnesium sheet, by the aspirin of recipe quantity, tartaric acid and
85g lactose mixes, with 10% starch slurry wet granulation, fluidized drying；Aspirin granule and 4g microcrystalline cellulose, 3.5g is sliding
Mountain flour mixes, tabletting, packet separation layer；By Dihydroxyaluminium Aminoacetate, heavy magnesium carbonate, aspartame 0.1g, sodium carboxymethylcellulose 5g and 5g
Lactose mixes, and water is added to soak, and is wrapped in label periphery, dry, both obtains 1000.This method uses wet granulation to aspirin,
The stability of aspirin is seriously affected, is easily decomposed.
Above method deposits various deficiencies, in order to overcome the shortcomings in the prior art, find a kind of pair of aspirin stabilization,
Simple process, the manufacturing method of dissolution are highly desirable.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing magnalium department double-layer tablets, bilayer tablet made from this method
Stability, not stratified, result of extraction is good.The inventors discovered that the stability of aspirin and the stabilization of tablet in magnalium department piece
Property (tablet layering) influenced during the preparation process by moisture and temperature, dissolution also influenced by auxiliary material, therefore, study and select
The process conditions such as suitable auxiliary material and temperature, moisture content are extremely important to the magnalium department bilayer tablet for producing high quality.
To achieve the purpose of the present invention, following embodiment is provided.
In one embodiment, a kind of method preparing magnalium department double-layer tablets of the invention, with 1000 with meter, including
Following steps:
1) by aspirin 330g, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose (LS~HPC) 8~15g, starch 30
~40g and 12~18g of talcum powder is uniformly mixed, and is put into tablet press machine tabletting to get A piece；
2) after dissolving 0.015~0.02g of lemon yellow with a small amount of purified water, 4~8g of starch is added, adds a small amount of purifying
Water stirs evenly, and boiling purified water is then added, and continues stirring to ripe slurry, is configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g and 10~15g of starch are uniformly mixed, the starch slurry of step 2) are added,
Wet granulation crosses the granulation of 16 meshes, is dried to obtain dry particl；
4) dry particl and 6~10g of talcum powder are uniformly mixed, are added to the A on piece of step 1), tabletting up to double-layer tablets,
Wherein, the drying in the step 3), drying temperature are 60 DEG C~70 DEG C, after pellet moisture≤3%, are blown a cold wind over
Temperature is down to 40 DEG C or less, preferably 40 DEG C.
In the above-described embodiment, it is preferred that method of the invention, in step 1), low-substituted hydroxypropyl cellulose is
10g, starch 37g or talcum powder are 15g；In step 2), lemon yellow is 0.017g or starch is 6g；In step 3), starch is
12g；In step 4), talcum powder 8g.
In one embodiment, a kind of method preparing magnalium department double-layer tablets of the invention, with 1000 with meter,
The following steps are included:
1) by aspirin 330g, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 10g, starch 37g and talcum powder 15g
It is uniformly mixed, is put into tablet press machine tabletting to get A piece；
2) after dissolving lemon yellow 0.017g with a small amount of purified water, starch 6g is added, adds a small amount of purified water and stirs evenly, so
Boiling purified water is added afterwards, continues stirring to ripe slurry, is configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g and starch 12g are uniformly mixed, the starch slurry of step 2), wet process is added
16 meshes are crossed in granulation, and particle is dry at a temperature of 60 DEG C~70 DEG C, and after pellet moisture≤3%, temperature of blowing a cold wind over is down to 40 DEG C
Or it is following, obtain dry particl；
4) dry particl and talcum powder 8g are uniformly mixed, are added to the A on piece of step 1), tabletting is up to double-layer tablets.
Magnalium department bilayer tablet, not stratified made from method of the invention, and aspirin stability, result of extraction is good, has
Conducive to aspirin in small intestinal absorption, the stimulation and damage to stomach are avoided.
Detailed description of the invention
Fig. 1 is time~accumulative dissolution curve of embodiment 1, the double-layer tablets of comparative example 5 and 7.
Specific embodiment
Following embodiment is not limited the scope of the invention for further understanding essence of the invention with this.
Embodiment 1
The preparation of magnalium department double-layer tablets, with 1000 with meter, preparation process is as follows:
1) aspirin 330g is sieved with 100 mesh sieve, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 10g, starch 37g and
Talcum powder 15g is uniformly mixed, and is put into tablet press machine tabletting to get A piece；
2) after dissolving lemon yellow 0.017g with a small amount of purified water, starch 6g is added, adds a small amount of purified water and stirs evenly, so
Boiling purified water is added afterwards, continues stirring to ripe slurry, is configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g are crushed, crosses 40 meshes, is uniformly mixed with starch 12g, be added a small amount of
The starch slurry high-speed stirred of step 2) is cut 200 seconds, is then gradually drenched into remaining starch slurry, high-speed stirred, cutting 60 seconds, system
Grain crosses 16 meshes, and particle is dry at a temperature of 60 DEG C~70 DEG C, after pellet moisture≤3%, stops heating, temperature of blowing a cold wind over
40 DEG C are down to, dry particl is obtained；
4) dry particl and talcum powder 8g are uniformly mixed, are added to the A on piece of step 1), tabletting is up to double-layer tablets 1000
Piece.
Double-layer tablets made from step 4) are aluminum-plastic packaged.
Embodiment 2
The preparation of magnalium department double-layer tablets, with 1000 with meter, preparation process is as follows:
1) aspirin 330g is sieved with 100 mesh sieve, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 8g, starch 40g and cunning
Mountain flour 12g is uniformly mixed, and is put into tablet press machine tabletting to get A piece；
2) after dissolving lemon yellow 0.015g with a small amount of purified water, starch 4g is added, adds a small amount of purified water and stirs evenly, so
Boiling purified water is added afterwards, continues stirring to ripe slurry, is configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g are crushed, crosses 40 meshes, is uniformly mixed with starch 10g, be added a small amount of
The starch slurry high-speed stirred of step 2) is cut 200 seconds, is then gradually drenched into remaining starch slurry, high-speed stirred, cutting 60 seconds, system
Grain crosses 16 meshes, and particle is dry at a temperature of 60 DEG C~70 DEG C, after pellet moisture≤3%, stops heating, temperature of blowing a cold wind over
40 DEG C are down to, dry particl is obtained；
4) dry particl and talcum powder 10g are uniformly mixed, are added to the A on piece of step 1), tabletting is up to double-layer tablets 1000
Piece.
Double-layer tablets made from step 4) are aluminum-plastic packaged.
Embodiment 3
The preparation of magnalium department double-layer tablets, with 1000 with meter, preparation process is as follows:
1) aspirin 330g is sieved with 100 mesh sieve, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 15g, starch 30g and
Talcum powder 18g is uniformly mixed, and is put into tablet press machine tabletting to get A piece；
2) after dissolving lemon yellow 0.02g with a small amount of purified water, starch 8g is added, adds a small amount of purified water and stirs evenly, so
Boiling purified water is added afterwards, continues stirring to ripe slurry, is configured to 10% starch slurry；
3) by heavy magnesium carbonate 100g and Dihydroxyaluminium Aminoacetate 50g, 40 meshes is crossed, are uniformly mixed with starch 15g, step 2) is added
Starch slurry, wet granulation cross the granulation of 16 meshes, and particle is dry at a temperature of 60 DEG C~70 DEG C, after pellet moisture≤3%, stops
It only heats, temperature of blowing a cold wind over is down to 40 DEG C, obtains dry particl；
4) dry particl and talcum powder 6g are uniformly mixed, are added to the A on piece of step 1), tabletting is up to double-layer tablets 1000
Piece.
Double-layer tablets made from step 4) are aluminum-plastic packaged.
Comparative example 1
The preparation of magnalium department double-layer tablets, with 1000 with meter, preparation process is as follows:
1) aspirin 330g is sieved with 100 mesh sieve, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 8g, starch 40g and cunning
Mountain flour 12g is uniformly mixed, and is put into tablet press machine tabletting to get A piece；
2) after dissolving lemon yellow 0.015g with a small amount of purified water, starch 4g is added, adds a small amount of purified water and stirs evenly, so
Boiling purified water is added afterwards, continues stirring to ripe slurry, is configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g are crushed, crosses 40 meshes, is uniformly mixed with starch 10g, be added a small amount of
The starch slurry high-speed stirred of step 2) is cut 200 seconds, is then gradually drenched into remaining starch slurry, high-speed stirred, cutting 60 seconds, system
Grain crosses 16 meshes, and particle is dry at a temperature of 85 DEG C, after pellet moisture≤3%, stops heating, temperature of blowing a cold wind over is down to 40
DEG C, obtain dry particl；
4) dry particl and talcum powder 10g are uniformly mixed, are added to the A on piece of step 1), tabletting is up to double-layer tablets 1000
Piece.
Tablet made from step 4) is aluminum-plastic packaged.
Comparative example 2~6
For the double-layer tablets of comparative example 2~6 in addition to the parameter change of following table, other preparation processes are identical as comparative example 1.
The prescription and technological parameter of the double-layer tablets of 1 comparative example 2~6 of table
4 Stability Determination of embodiment
The magnalium department double-layer tablets (aluminum-plastic packaged) that embodiment 1, the method for comparative example 1~4 and 6 are obtained, carry out accelerating 3
Moon study on the stability test (RH75 ± 5%, 40 ± 2 DEG C).Investigation tablet, which whether there is to divide, to be deposited, and uses high performance liquid chromatography
(referring to two annex VD of Chinese Pharmacopoeia version in 2010) measurement aspirin content and the salicylic content of impurity.It the results are shown in Table
2 and table 3.
The double-layer tablets study on the stability result of 2 embodiment 1 of table and comparative example 1~2
The double-layer tablets study on the stability result of 3 comparative example 3~4 and 6 of table
Table 2 and table 3 statistics indicate that, magnalium department double-layer tablets of the invention are stablized without lamination, aspirin, water impurity
Poplar acid content is low.And there is lamination (comparative example 1~4) in comparative example 1~4 and 6, stability test, impurity salicylic acid content
More than 1% or more, comparative example 1 and 2 causes aspirin to be degraded since drying temperature is higher or relatively low, especially comparative example 3
Double-layer tablets cause aspirin degradation serious during the preparation process since moisture content has been greater than 3%.And comparative example 4 and 6
In the identical situation of preparation process condition, because supplementary product kind is variant, aspirin stabilization is also had an impact.As it can be seen that aluminium
The stability of magnesium department double-layer tablets has correlation with supplementary product kind and preparation process condition (drying temperature and moisture content).The present invention
Method show very excellent effect.
The double-layer tablets for investigating embodiment 2~3 in the same way, obtain effect similar to Example 1.
6 dissolution determination of embodiment
The measuring method of dissolution rate, the magnalium department double-layer tablets of Example 1, comparative example 5 and 7, according to Chinese Pharmacopoeia 2010
Year two the first methods of annex X of version, using dilute hydrochloric acid solution as dissolution medium, revolving speed is 100 turns, using high performance liquid chromatography (in
Two annex VD of state's pharmacopeia version in 2010) measurement.It the results are shown in Table 4 and Fig. 1.
4 degree of measuring measurement result of table
* comparative example 7 is the magnalium department double-layer tablets obtained by the method for CN101632647A specification embodiment 4.
Table 4 the result shows that, comparative example 7 due to be added lauryl sodium sulfate surfactant, aspirin discharge too
Fastly, it is excessively high that Aspirin concentrations in stomach as a result be will lead to, stimulation and damage are generated to stomach, dodecyl is not added in comparative example 5
Sulfuric acid natrium surfactant, but dissolved out double-layer tablets (embodiment 1) aspirin rate of release that slow, of the invention method obtains
It is moderate, it is excessively high not will lead to Aspirin concentrations in stomach, and be conducive to be transferred to small intestinal absorption.
On the basis of connotation of the invention, simple flexible or modification is carried out, or according to production scale by each ingredient
(recipe quantity) becomes smaller or larger at double, also belongs to the scope of the present invention.
Claims (1)
1. a kind of method for preparing magnalium department double-layer tablets, with 1000 with meter, comprising the following steps:
1) aspirin 330g, tartaric acid 3.3g, low-substituted hydroxypropyl cellulose 10g, starch 37g and talcum powder 15g are mixed
Uniformly, tabletting is put into tablet press machine to get A piece；
2) by lemon yellow 0.017g with a small amount of purified water dissolve after, be added starch 6g, add a small amount of purified water and stir evenly, then plus
Enter to boil purified water, continues stirring to ripe slurry, be configured to 10% starch slurry；
3) heavy magnesium carbonate 100g, Dihydroxyaluminium Aminoacetate 50g and starch 12g are uniformly mixed, the starch slurry of step 2), wet process system is added
Grain crosses the granulation of 16 meshes, is dried to obtain dry particl；
4) dry particl and talcum powder 8g are uniformly mixed, are added to the A on piece of step 1), tabletting up to double-layer tablets,
Wherein, the drying in the step 3), drying temperature are 60 DEG C~70 DEG C, after pellet moisture≤3%, temperature of blowing a cold wind over
40 DEG C or less are down to up to dry particl.
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| CN112190560A (en) * | 2020-11-16 | 2021-01-08 | 仁和堂药业有限公司 | Aluminum hydroxide tablet and production method thereof |
| CN113230221B (en) * | 2021-04-06 | 2022-11-04 | 北京诚济制药股份有限公司 | Aluminum magnesium pilin tablet (II) |
| CN116059385B (en) * | 2023-03-13 | 2025-02-11 | 山东中健康桥制药有限公司 | Aluminum-magnesium aspirin pharmaceutical composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101632647A (en) * | 2008-07-21 | 2010-01-27 | 北京迈劲医药科技有限公司 | Preparation method for compound preparation comprising aspirin and alkaline drugs |
| CN102793718A (en) * | 2011-05-22 | 2012-11-28 | 符靠 | Pharmaceutical composition including aspirin salt and aluminium magnesium salt |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101632647A (en) * | 2008-07-21 | 2010-01-27 | 北京迈劲医药科技有限公司 | Preparation method for compound preparation comprising aspirin and alkaline drugs |
| CN102793718A (en) * | 2011-05-22 | 2012-11-28 | 符靠 | Pharmaceutical composition including aspirin salt and aluminium magnesium salt |
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| Title |
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| 阿司匹林铝碳酸镁双层片的制备及质量研究;肖慧等;《中国新药杂志》;20131231;第22卷(第18期);全文 |
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