CN112843008A - Acetylcysteine tablet and preparation method thereof - Google Patents
Acetylcysteine tablet and preparation method thereof Download PDFInfo
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- CN112843008A CN112843008A CN202110171002.7A CN202110171002A CN112843008A CN 112843008 A CN112843008 A CN 112843008A CN 202110171002 A CN202110171002 A CN 202110171002A CN 112843008 A CN112843008 A CN 112843008A
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- Prior art keywords
- acetylcysteine
- tablet
- pharmaceutically acceptable
- weight
- tablets
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- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 title claims abstract description 108
- 229960004308 acetylcysteine Drugs 0.000 title claims abstract description 104
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 14
- 229920001531 copovidone Polymers 0.000 claims abstract description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 11
- 239000000843 powder Substances 0.000 claims abstract description 11
- 239000000853 adhesive Substances 0.000 claims abstract description 10
- 230000001070 adhesive effect Effects 0.000 claims abstract description 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 9
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 8
- 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 abstract description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 8
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 8
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 7
- 238000005469 granulation Methods 0.000 claims abstract description 7
- 230000003179 granulation Effects 0.000 claims abstract description 7
- -1 polyoxyethylene Polymers 0.000 claims abstract description 7
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims abstract description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 5
- 239000011230 binding agent Substances 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000007908 dry granulation Methods 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 238000005550 wet granulation Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 238000003825 pressing Methods 0.000 claims description 5
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- 235000012239 silicon dioxide Nutrition 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 238000007907 direct compression Methods 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
- 229960000913 crospovidone Drugs 0.000 claims description 3
- 239000007884 disintegrant Substances 0.000 claims description 3
- 229940057948 magnesium stearate Drugs 0.000 claims description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 2
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 2
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
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- 229940005550 sodium alginate Drugs 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
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- 235000001465 calcium Nutrition 0.000 claims 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 11
- 239000008187 granular material Substances 0.000 abstract description 9
- 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 abstract description 5
- 229920013819 hydroxyethyl ethylcellulose Polymers 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 3
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
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- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
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- 108010024636 Glutathione Proteins 0.000 description 2
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- 230000000996 additive effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
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- 238000013112 stability test Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- VQYLPBZKTJXVAA-WUCPZUCCSA-N (2r)-2-amino-4-oxo-3-sulfanylpentanoic acid Chemical compound CC(=O)C(S)[C@H](N)C(O)=O VQYLPBZKTJXVAA-WUCPZUCCSA-N 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
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- 102100025981 Aminoacylase-1 Human genes 0.000 description 1
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- 244000025254 Cannabis sativa Species 0.000 description 1
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- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
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- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 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 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
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- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 229960003920 cocaine Drugs 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
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- 150000001944 cysteine derivatives Chemical group 0.000 description 1
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- 230000009982 effect on human Effects 0.000 description 1
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Classifications
-
- 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
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- General Health & Medical Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
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- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an acetylcysteine tablet and a preparation method thereof. The acetylcysteine tablet provided by the invention contains at least 65% of acetylcysteine, 2-30% of adhesive and other pharmaceutically acceptable auxiliary materials per unit of acetylcysteine tablet. The invention creatively adds one or more of acetylcysteine and copovidone, polyoxyethylene, polyvinyl alcohol, hydroxyethyl cellulose, ethyl cellulose and sodium carboxymethyl cellulose into other pharmaceutically acceptable medicinal auxiliary materials according to the requirement to carry out dry method, wet method or fluidized bed granulation, or directly mixes acetylcysteine and the auxiliary materials to prepare the acetylcysteine tablets with good granule or powder fluidity, smooth appearance, uniform dissolution and good stability.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a high-proportion active ingredient acetylcysteine and an adhesive for improving the formability of the active ingredient.
Background
Acetylcysteine, also known as N-acetylcysteine or N-acetyl-L-cysteine or NAC, is used primarily as a mucolytic agent and in the management of acetaminophen poisoning. It is a derivative of cysteine, the acetyl group of which is linked to the amino group of cysteine. NAC is essentially a prodrug that is converted to cysteine (by the aminoacylase 1 enzyme in the intestine) and absorbed into the bloodstream in the intestine. Cysteine is a key component of glutathione and therefore administration of acetylcysteine supplements the glutathione depot. Acetylcysteine may also be used as a general antioxidant, and may help alleviate symptoms of a variety of diseases exacerbated by Reactive Oxygen Species (ROS). For example, acetylcysteine is commonly used in people with renal insufficiency to prevent the precipitation of acute renal failure. Acetylcysteine has been shown to be effective in treating mild to moderate traumatic brain injury (including ischemic brain injury), particularly in reducing neuronal loss, and also to alleviate cognitive and neurological symptoms when administered immediately after injury. N-acetylcysteine is now widely used in the treatment of HIV, and it has been reported to treat chronic obstructive pulmonary disease and contrast-induced nephropathy. Acetylcysteine has also been successfully used in the treatment of a variety of neuropsychiatric and neurodegenerative diseases, including cocaine, marijuana and smoking addiction, alzheimer's and parkinson's diseases, autism, obsessive-compulsive and modifying disorders, schizophrenia, depression, and bipolar disorders. The acetylcysteine tablet agents which are marketed comprise acetylcysteine tablets and acetylcysteine effervescent tablets, but the preparation processes comprise wet granulation, and acetylcysteine has poor chemical stability, is easy to oxidize and hydrolyze, and generates unpleasant sulfur smell.
Italy Zambon company applied for patent WO2014/191410A1 and disclosed a swallowable tablet of N-acetylcysteine, which was prepared by dry granulation of acetylcysteine alone and then mixing with other excipients for compression, thus improving the odor problem. However, the tablets obtained in this way have poor flowability of the granules, a non-smooth appearance and poor dissolution uniformity. Therefore, in the prior art, the technical problems mostly solved for the application and preparation process of acetylcysteine still exist, and related patents and reports for preparing acetylcysteine tablets by a powder direct pressing mode are not provided.
Therefore, how to improve the application of acetylcysteine and improve the uniformity and storage stability of acetylcysteine dissolution is a problem to be solved urgently at present.
Disclosure of Invention
In order to solve the problems in the prior art, the invention aims to provide an acetylcysteine tablet and a preparation method thereof. The acetylcysteine tablet provided by the invention is prepared by pressing acetylcysteine, an adhesive and other pharmaceutically acceptable auxiliary materials in a dry granulation mode, a powder direct-pressing mode, a fluidized bed granulation mode or a wet granulation mode, and the granules and the powder have good flowability, smooth appearance, uniform dissolution and good storage stability.
The technical scheme of the invention is as follows:
an acetylcysteine tablet, each unit of acetylcysteine tablet contains at least 65% of acetylcysteine, 2-30% of adhesive and other pharmaceutically acceptable auxiliary materials.
Furthermore, each unit of the acetylcysteine tablet comprises at least 65-90% by weight of acetylcysteine, 2-30% by weight of a binder and other pharmaceutically acceptable auxiliary materials.
Furthermore, each unit of the acetylcysteine tablet comprises at least 65-90% by weight of acetylcysteine, 3-20% by weight of a binder and other pharmaceutically acceptable auxiliary materials.
Furthermore, each unit of the acetylcysteine tablet is prepared from 80% by weight of acetylcysteine, 8% by weight of adhesive and 12% of other pharmaceutically acceptable auxiliary materials.
Further, the adhesive is one or more of copovidone, polyoxyethylene, polyvinyl alcohol, ethyl cellulose, hydroxyethyl cellulose and sodium carboxymethyl cellulose.
Further, the pharmaceutically acceptable other auxiliary materials comprise a filler, a disintegrant, a lubricant and a glidant.
Further, the filler is one or more of microcrystalline cellulose, calcium sulfate and calcium carbonate.
Further, the disintegrating agent is one or more of crospovidone, carboxymethyl starch sodium, sodium alginate and carboxymethyl cellulose calcium.
Further, the lubricant is one or more of magnesium stearate, polyethylene glycol 4000, polyethylene glycol 6000 and magnesium lauryl sulfate.
Further, the glidant is silicon dioxide.
In addition, the invention also provides a preparation method of the acetylcysteine tablet, which comprises the following steps: and (3) carrying out dry granulation, powder direct compression, fluidized bed granulation or wet granulation on acetylcysteine, an adhesive and other pharmaceutically acceptable auxiliary materials to obtain the tablet.
In order to solve the problems of unsmooth appearance, poor dissolution uniformity, poor storage stability and the like of acetylcysteine tablets prepared by dry granulation in the prior art, the inventors of the present application have conducted intensive research and made a great deal of creative experiments to find that acetylcysteine tablets with more stable physical and chemical properties can be prepared when the binder used in the acetylcysteine tablets prepared by the present invention is one or more of copovidone, polyoxyethylene, polyvinyl alcohol, ethyl cellulose, hydroxyethyl cellulose and sodium carboxymethyl cellulose. The copovidone has good water solubility, cohesiveness and film forming property, lower water absorption, wider solubility, better plasticity and stronger surface activity, is an excellent tablet adhesive, and the tablet prepared by the copovidone has the characteristics of high hardness and low friability, can be tabletted under a humid condition with less adhesion, and is particularly suitable for tabletting and granulating high-dosage, poor water solubility and water-sensitive medicaments. Polyvinyl alcohol is a safe polymer organic matter, has no toxicity or side effect on human bodies, has good biocompatibility, and can be used as a binding agent of tablets by using low-concentration polyoxyethylene. The ethyl cellulose can be used as a binding agent of tablets after being mixed by a dry method or a wet method, and the tablets prepared by the ethyl cellulose are hard and have low brittleness. Sodium carboxymethyl cellulose is commonly used as a binder for tablets, and is also widely used in cosmetics and foods, and is generally considered as a substance having no toxicity or irritation. Hydroxyethyl cellulose is a non-ionic water-soluble polymer material, is widely used in pharmaceutical preparations, is mainly used as a thickening agent of ophthalmic preparations and topical preparations, a binding agent of tablets and a film coating material, is not influenced by the pH value of the environment, and has stable property. Therefore, several auxiliary materials can be selected as the adhesive of the invention.
Therefore, one or more of acetylcysteine and copovidone, polyoxyethylene, polyvinyl alcohol, hydroxyethyl cellulose, ethyl cellulose and sodium carboxymethylcellulose are used, and other pharmaceutically acceptable auxiliary materials are added to carry out dry granulation, powder direct compression, fluidized bed granulation or wet granulation, so that the flowability of granules or powder can be improved, the obtained tablet has smooth appearance and dissolution uniformity, and the cumulative dissolution rate within 15min is more than 90%. Meanwhile, the acetylcysteine tablet prepared by the invention is tested and examined for 6 months under the condition of 40 ℃/RH 75% at an accelerated speed, and the result shows that the tablet has less related total impurities and better stability.
Compared with the prior art, the acetylcysteine provided by the invention has the following advantages:
(1) the invention creatively adds one or more of acetylcysteine and copovidone, polyoxyethylene, polyvinyl alcohol, hydroxyethyl cellulose, ethyl cellulose and sodium carboxymethyl cellulose into other pharmaceutically acceptable pharmaceutical excipients according to the requirement to carry out dry granulation, powder direct compression, fluidized bed granulation or wet granulation, and prepares the acetylcysteine tablets with good granule or powder fluidity, smooth appearance, dissolution uniformity and good stability.
(2) The acetylcysteine tablet provided by the invention can be produced by adopting a general tablet process, is simple and easy to operate, effectively solves the problems of poor formability and stability of the acetylcysteine tablet in the prior art in the preparation process, and is beneficial to popularization and application of acetylcysteine.
Detailed Description
The present invention is further illustrated by the following description of specific embodiments, which are not intended to limit the invention, and various modifications and improvements can be made by those skilled in the art based on the basic idea of the invention, but the invention is within the protection scope of the invention.
Wherein, the reagents used in the invention are all common reagents and can be purchased from common reagent production and sale companies.
Example 1 acetylcysteine tablet and method for preparing the same
TABLE 1 formulation of acetylcysteine tablets
The preparation process of the acetylcysteine tablet comprises the following steps of dry granulation: weighing the raw materials and auxiliary materials according to the prescription amount of 1000 tablets, and respectively sieving. Then mixing acetylcysteine with copovidone, silicon dioxide (internal addition) and magnesium stearate (internal addition), performing dry granulation, mixing the obtained granules with other adjuvants, and tabletting.
Example 2 acetylcysteine tablet and method for preparing the same
TABLE 2 formulation of acetylcysteine tablets
The preparation process of the acetylcysteine tablet comprises the following steps of dry granulation: weighing the raw materials and auxiliary materials according to the prescription amount of 1000 tablets, and respectively sieving. Mixing acetylcysteine, polyvinyl alcohol, microcrystalline cellulose, sodium carboxymethyl starch, silicon dioxide (internal additive) and magnesium stearate (internal additive), granulating by dry method, mixing the obtained granule with the rest adjuvants, and tabletting.
Example 3 acetylcysteine tablet and method for preparing the same
TABLE 3 formulation of acetylcysteine tablets
The preparation process of the acetylcysteine tablet comprises the following steps of wet granulation: weighing the raw materials and auxiliary materials according to the prescription amount of 1000 tablets, and respectively sieving. Adding acetylcysteine, microcrystalline cellulose and sodium carboxymethylcellulose into a rapid wet granulator, mixing, spraying purified water for granulating, drying with a fluidized bed, mixing the obtained granules with other adjuvants, and tabletting.
Example 4 acetylcysteine tablet and method for preparing the same
TABLE 4 formulation of acetylcysteine tablets
The preparation process of the acetylcysteine tablet is a fluidized bed granulation method: weighing the raw materials and auxiliary materials according to the prescription amount of 1000 tablets, and respectively sieving. Placing acetylcysteine in fluidized bed, adjusting air volume, temperature, spray speed and atomization pressure, spraying 10% copovidone water solution for granulating, mixing the obtained granule with other adjuvants, and tabletting.
Example 5 acetylcysteine tablet and method for preparing the same
TABLE 5 formulation of acetylcysteine tablets
The preparation process of the acetylcysteine tablet is a powder direct pressing method: weighing raw and auxiliary materials according to the prescription amount of 1000 tablets, respectively sieving, uniformly mixing acetylcysteine and copovidone, microcrystalline cellulose, crospovidone, magnesium stearate and silicon dioxide, and directly tabletting.
Test example I dissolution test of acetylcysteine sheet
1. Test materials: acetylcysteine tablets obtained in examples 1 to 5.
2. The test method comprises the following steps: according to a dissolution rate determination method (addition XC in the second part of the Chinese pharmacopoeia 2010 edition), 500ml of 0.1M hydrochloric acid solution is used as a dissolution medium, the temperature is 37 ℃, the slurry method is adopted, the rotating speed is 50rpm, the dissolution performance of acetylcysteine is evaluated, and the experimental result is recorded.
3. Test results
The test results are shown in table 6.
TABLE 6 dissolution Profile of acetylcysteine tablets
The dissolution test results in table 6 show that: according to the tablet prepared in the embodiment 1-5, more than 85% of acetylcysteine can be dissolved out within 10min, more than 90% of acetylcysteine can be dissolved out within 15min, and the dissolving uniformity is good, so that the acetylcysteine prepared according to the formula and the preparation method provided by the invention has good dissolving behavior.
Test example II stability test of acetylcysteine tablet
1、Test materials: acetylcysteine tablets obtained in examples 1 to 5, commercially available products
Acetylcysteine tablets (manufactured by Hainan Zabang pharmaceutical Co., Ltd.).
2. The test method comprises the following steps: acetylcysteine tablets prepared in embodiments 1-5 of the invention and marketed products
Acetylcysteine tablets (manufactured by Hainan Zabang pharmaceutical Co., Ltd.) were left at 40 ℃ and RH 75% for 6 months, and subjected to accelerated tests to determine the total hybridization change of each.
3. Test results
The test results are shown in Table 7.
TABLE 7 Total miscellaneous Change of acetylcysteine tablets under accelerated conditions
The stability test results of the accelerated test in Table 7 show that the acetylcysteine tablets prepared in examples 1 to 5 of the present invention are comparable to those of acetylcysteine tablets prepared in the accelerated test of the present invention
The initial impurity content of the tablet is small, and the acetylcysteine tablets of embodiments 1-5 of the invention are placed for 6 months at the temperature of 40 ℃ and RH 75%, and the increase of the impurity after the accelerated test is less than that of the tablet
Tablet showing good storage stability。
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. An acetylcysteine tablet, characterized in that each unit of acetylcysteine tablet contains at least 65% by weight of acetylcysteine, 2% -30% by weight of adhesive and other pharmaceutically acceptable auxiliary materials.
2. The acetylcysteine tablet according to claim 1, wherein each unit of the acetylcysteine tablet comprises at least 65-90% by weight of acetylcysteine, 2-30% by weight of binder and other pharmaceutically acceptable excipients.
3. The acetylcysteine tablet according to claim 2, wherein each unit of the acetylcysteine tablet is made of 80% by weight of acetylcysteine, 8% by weight of binder and 12% other pharmaceutically acceptable excipients.
4. The acetylcysteine tablet of claim 1, wherein the binder is one or more of copovidone, polyoxyethylene, polyvinyl alcohol, ethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose.
5. The acetylcysteine tablet of claim 1, wherein the pharmaceutically acceptable additional excipients include fillers, disintegrants, lubricants, and glidants.
6. The acetylcysteine tablet of claim 5, wherein the filler is one or more of microcrystalline cellulose, calcium sulfate, and calcium carbonate.
7. The acetylcysteine tablet of claim 5, wherein the disintegrant is one or more of crospovidone, sodium carboxymethyl starch, sodium alginate, and calcium carboxymethyl cellulose.
8. The acetylcysteine tablet of claim 5, wherein the lubricant is one or more of magnesium stearate, polyethylene glycol 4000, polyethylene glycol 6000, and magnesium lauryl sulfate.
9. Acetylcysteine tablet according to claim 5, wherein the glidant is silicon dioxide.
10. The method for preparing acetylcysteine tablet according to any one of claims 1-9, wherein the preparation method comprises pressing acetylcysteine, binder and other pharmaceutically acceptable excipients into tablet by dry granulation, powder direct compression, fluidized bed granulation or wet granulation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114886860A (en) * | 2022-06-28 | 2022-08-12 | 山东达因海洋生物制药股份有限公司 | Acetylcysteine pharmaceutical composition, preparation and preparation process thereof |
| CN115177593A (en) * | 2022-08-08 | 2022-10-14 | 锦州奥鸿药业有限责任公司 | Glutamine granules and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1345236A (en) * | 1999-04-06 | 2002-04-17 | 萨宝集团公司 | Swallowable tablets with high content of N-acetylcysteine |
| CN105228595A (en) * | 2013-05-29 | 2016-01-06 | 萨宝公司 | Deglutible N-acetylcystein tablet |
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2021
- 2021-02-07 CN CN202110171002.7A patent/CN112843008A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1345236A (en) * | 1999-04-06 | 2002-04-17 | 萨宝集团公司 | Swallowable tablets with high content of N-acetylcysteine |
| CN105228595A (en) * | 2013-05-29 | 2016-01-06 | 萨宝公司 | Deglutible N-acetylcystein tablet |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114886860A (en) * | 2022-06-28 | 2022-08-12 | 山东达因海洋生物制药股份有限公司 | Acetylcysteine pharmaceutical composition, preparation and preparation process thereof |
| CN114886860B (en) * | 2022-06-28 | 2023-04-25 | 山东达因海洋生物制药股份有限公司 | Acetylcysteine pharmaceutical composition, preparation and preparation process thereof |
| CN115177593A (en) * | 2022-08-08 | 2022-10-14 | 锦州奥鸿药业有限责任公司 | Glutamine granules and preparation method thereof |
| CN115177593B (en) * | 2022-08-08 | 2023-08-25 | 锦州奥鸿药业有限责任公司 | Glutamine granule and preparation method thereof |
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Application publication date: 20210528 |