CN109248150A - A kind of amoxicillin and clavulanate potassium preparation and preparation method thereof - Google Patents
A kind of amoxicillin and clavulanate potassium preparation and preparation method thereof Download PDFInfo
- Publication number
- CN109248150A CN109248150A CN201710569445.5A CN201710569445A CN109248150A CN 109248150 A CN109248150 A CN 109248150A CN 201710569445 A CN201710569445 A CN 201710569445A CN 109248150 A CN109248150 A CN 109248150A
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- clavulanate
- dispersible tablet
- potassium
- sorbierite
- 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.)
- Granted
Links
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 title claims abstract description 68
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 67
- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 65
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 229940038649 clavulanate potassium Drugs 0.000 title claims abstract description 28
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 30
- 229920000858 Cyclodextrin Polymers 0.000 claims description 24
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 21
- 239000001116 FEMA 4028 Substances 0.000 claims description 21
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 21
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 21
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 21
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 21
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 21
- 229960004853 betadex Drugs 0.000 claims description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 21
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 21
- 229920002472 Starch Polymers 0.000 claims description 20
- 239000008107 starch Substances 0.000 claims description 20
- 235000019698 starch Nutrition 0.000 claims description 20
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 19
- 239000011734 sodium Substances 0.000 claims description 16
- 229910052708 sodium Inorganic materials 0.000 claims description 16
- 229960000913 crospovidone Drugs 0.000 claims description 15
- 235000019359 magnesium stearate Nutrition 0.000 claims description 15
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 15
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 238000005469 granulation Methods 0.000 claims description 11
- 230000003179 granulation Effects 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
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- 239000000853 adhesive Substances 0.000 claims description 4
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- 239000007853 buffer solution Substances 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 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 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 238000002390 rotary evaporation Methods 0.000 claims description 3
- -1 sorbierite Chemical compound 0.000 claims description 3
- 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 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- 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 2
- 239000008103 glucose Substances 0.000 claims description 2
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims 4
- 229920001353 Dextrin Polymers 0.000 claims 1
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- 229920002678 cellulose Polymers 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
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- 235000019425 dextrin Nutrition 0.000 claims 1
- 238000005461 lubrication Methods 0.000 claims 1
- 235000021017 pears Nutrition 0.000 claims 1
- 229940080313 sodium starch Drugs 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 4
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- 235000009508 confectionery Nutrition 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000011812 mixed powder Substances 0.000 description 4
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229940038195 amoxicillin / clavulanate Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 3
- 229960003324 clavulanic acid Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 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
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- QJVHTELASVOWBE-AGNWQMPPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 QJVHTELASVOWBE-AGNWQMPPSA-N 0.000 description 2
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- IIEJGTQVBJHMDL-UHFFFAOYSA-N 2-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-[2-oxo-2-[3-(sulfamoylamino)pyrrolidin-1-yl]ethyl]-1,3,4-oxadiazole Chemical compound C1CN(CC1NS(=O)(=O)N)C(=O)CC2=NN=C(O2)C3=CN=C(N=C3)NC4CC5=CC=CC=C5C4 IIEJGTQVBJHMDL-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
-
- 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
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Abstract
The invention belongs to pharmaceutical technology fields, and the present invention provides a kind of amoxicillin and clavulanate potassium preparations and preparation method thereof.The stability of the dispersible tablet of the technology of the present invention preparation, amoxicillin and clavulanate potassium improves, and result of extraction is preferable, and related substance is lower.The method of the present invention effectively shortens process flow, reduces production cycle and drug exposure duration in air, guarantees the stability of drug, further improve the quality of product.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of amoxicillin and clavulanate potassium preparation and preparation method thereof
Background technique
Amoxicillin also known as amoxicillin or Amoxicillin, molecular formula C16H19N3O5S, molecular weight 365.4042.It is one
The most common semi-synthetic penicillins wide spectrum beta-lactam antibiotic of kind, is a kind of white powder, half-life period is about 61.3 points
Clock.It is one of current widely used oral semisynthetic penicillin, potassium clavulanate, molecular formula C8H8KNO5, molecular weight
It is 237.25, chemical name is (Z)-(2R, 5R) -3- (2- hydroxyl ethylidene) -7- oxo -4- oxa- -1- azabicyclo -3.2.0-
Heptane -2- carboxylic acid potassium.It is calculated by anhydride, contains clavulanic acid (C8H9NO5) 81.0~85.6%.Amoxicillin and clavulanic acid
The ratio of potassium has 2:1,4:1,5:1,7:1,10:1,14:1 and 16:1 etc., and ratio is in terms of Amoxicillin and clavulanic acid.
Amoxicillin and clavulanate potassium dispersible tablet peritonitis caused by the sensitive bacteria, skin and soft tissue infection,
The various infection such as otitis, osteomyelitis, cystitis, pelvic inflammatory disease.The antimicrobial spectrum of this product is identical as Amoxicillin, and is expanded.It is right
Producing enzyme staphylococcus aureus, staphylococcus epidermis, coagulase-negative staphylococci and enterococcus have good action, to certain
Producing the intestines liver Rhizobiaceae bacterium of beta-lactamase, haemophilus influenzae, moraxelle catarrhalis, bacteroides fragilis etc. also has preferable antibacterial living
Property.This product produces the enterobacteriaceae lactobacteriaceae and vacation list of I type enzyme of Chromosome-encoded to methicillin-resistant Staphylococcus and Enterobacter etc.
Born of the same parents Pseudomonas is without effect.There are many reports in the related patents country about amoxicillin and clavulanate potassium, such as:
CN200810212280.7 discloses a kind of amoxicillin/clavulanate potassium 8: 1 and preparation method thereof.Not Ah not
8: 1 tablet of XiLin/potassium clavulanate is the amoxicillin/clavulanate potassium (8: 1) good with quality controllability, mixture homogeneity
Intermediate blended stock is main ingredient source, and the preparation method technique is relatively simple.
CN200910074500.9 discloses a kind of preparation method of amoxicillin and clavulanate potassium tablets, Amoxicillin
It is 120~135 parts, 40~45 parts of potassium clavulanate, 27~32 parts of microcrystalline cellulose, 1~3 part of croscarmellose sodium, micro-
1~3 part of powder silica gel, 2~4 parts of magnesium stearate；It is mixed with potassium clavulanate according to 4: 1 mass ratio after amoxicillin granulation
It closes, constitutes major ingredient；By excipient micro-silica gel, croscarmellose sodium (ADS) and microcrystalline cellulose according to equivalent gradually-increased
It mixes, then progressively increases to put into the mixer with major ingredient equivalent and mix 36~70 minutes；Mixed powder is subjected to tabletting.The preparation method will
After amoxicillin granules are mixed with potassium clavulanate, then all auxiliary materials are added with equivalent gradually-increased and are mixed, incorporation time compared with
Long, feeding requirement is more stringent, is difficult to control the stability of technique
CN101897701B discloses a kind of preparation process of amoxicillin and clavulanate potassium tablets, by amoxicillin granulation
Afterwards, it according to the mass ratio of 4:1, is mixed with potassium clavulanate, constitutes major ingredient；By excipient micro-silica gel, cross-linked carboxymethyl cellulose
Sodium and microcrystalline cellulose are mixed according to equivalent gradually-increased, then are progressively increased to put into the mixer with major ingredient equivalent and be mixed；By mixed powder into
Row tabletting.It is uniformly mixed after the granulation of Amoxicillin original powder, then with potassium clavulanate, hence improves the flowing of major ingredient itself
Property, phenomena such as effectively preventing capping caused by direct tablet compressing, sticking.However, which kind of granulation is the technology do not suggest that using
Mode, and how to improve the stability of potassium clavulanate.
CN100391456C discloses a kind of beta-cyclodextrin/amoxicillin inclusion compound and its composition with potassium clavulanate
And preparation process.Cyclodextrin is mixed with water, makes into suspended substance, Amoxicillin is added, is fully ground, cooling, filtering, solids
Dry preparation solid clathrates after washing.But Amoxicillin is beta-lactam structure, hydrolysis is easy, using cyclodextrin encapsulated skill
Art, using water as medium, the stability of Amoxicillin is difficult to ensure.
CN101502511A discloses a kind of amoxicillin/clavulanate potassium 8:1 piece and its preparation process, has selected Ah not
The 8:1 of XiLin and potassium clavulanate mixes powder, using dry granulation process.Equally, which does not refer to how solving clavulanic acid
The stability problem of potassium.
Summary of the invention
In order to overcome the disadvantages and deficiencies of the prior art, the primary purpose of the present invention is that providing a kind of Amoxicillin carat
Sour potassium dispersible tablets are tieed up, solve the problems, such as that dissolution is slow, stability is poor, preparation process is complicated in the prior art.
Specifically: the invention is realized in this way.
A kind of amoxicillin and clavulanate potassium dispersible tablet, is calculated with weight ratio:
Further, the ingredient of Amoxicillin and potassium clavulanate is limited, is calculated with weight ratio, preferred ratio are as follows:
It is further preferred that carrying out preferably to above-mentioned adjunct ingredient, each component ratio is as follows, is calculated with weight ratio:
The trehalose: Amoxicillin=0.05-0.5:1, preferably trehalose: Amoxicillin=0.25:1.
The potassium clavulanate: beta-cyclodextrin=0.5-1.5:1, preferably potassium clavulanate: beta-cyclodextrin=1:1.
The filler be lactose, glucose, mannitol, dextran, microcrystalline cellulose, in one in sorbierite or
It is a variety of.The preferably mixed object of sorbierite and lactose or sorbierite and microcrystalline cellulose.Sorbierite: lactose weight consumption ratio is 1:1-
8, preferably 1:4；Sorbierite and microcrystalline cellulose weight consumption ratio are 1:1-8, preferably 1:4.
The disintegrating agent is crospovidone, pre-paying starch, dried starch, low-substituted hydroxypropyl cellulose, carboxylic first shallow lake
One of powder sodium is a variety of, preferably the mixture of crospovidone and sodium carboxymethyl starch.
The filler is preferably microcrystalline cellulose and sorbierite, and disintegrating agent is preferably that crospovidone and carboxymethyl form sediment
Powder sodium, lubricant are preferably sorbierite or magnesium stearate.
The lubricant is one of magnesium stearate, sorbierite, calcium stearate, talcum powder or a variety of.
Preparation method the present invention provides amoxicillin and clavulanate potassium includes specific steps are as follows:
Suitable Amoxicillin and trehalose are dissolved in sodium citrate buffer solution, rotary evaporation, obtain trehalose and Ah
Adhesive granulation is added in the mixture of Amdinocillin, dry；Potassium clavulanate is pulverized and sieved, the anhydrous of beta-cyclodextrin is suspended in
In ethyl alcohol, ethyl alcohol is dried and removed, the potassium clavulanate of beta-cyclodextrin package is obtained, adds filler, disintegrating agent, lubricant pressure
Piece.
The pH value of the citrate buffer solution is 3-6, and preferred pH value is 4.5.
The adhesive is one of starch slurry, hydroxypropyl methylcellulose, PVP K30 or a variety of.Preferably poly- dimension
Ketone K30.
Compared with prior art, main advantage is amoxicillin and clavulanate potassium dispersible tablet of the invention:
Amoxicillin and trehalose are dissolved in buffer first, mixed after evaporation granulation, then with potassium clavulanate
Uniformly, so that the stability of amoxicillin and clavulanate potassium improves, related content of material is reduced.Then gathered by filtering out to be crosslinked
Ketone, sodium carboxymethyl starch are tieed up, the dispersibility and hygroscopicity of auxiliary material are further enhanced.Hereafter progressively increase again with major ingredient equivalent throwing
Enter mixing in mixing machine, so that material is integrally provided with good mobility, compressibility and resistance to water soak, thus effectively prevent
Phenomena such as capping caused by direct tablet compressing, sticking, the bright and clean beauty of its appearance of products made thereby, content and dissolution rate are stablized.
The method of the present invention effectively shortens process flow, reduces production cycle and drug exposure duration in air,
The stability for guaranteeing drug, further improves the quality of product.
Amoxicillin and clavulanate potassium dispersible tablet of the present invention has disintegration Rapid Stability good, in good taste, prescription
Simply, prescription mixed powder good fluidity, tableting processes not sticking the advantages that, amoxicillin and clavulanate potassium will be widely used in
In the formulation art of dispersible tablet.
Specific embodiment
Embodiment 1:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 40g,
Sorbierite: 10g, crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
(a) suitable Amoxicillin and trehalose are dissolved in the sodium citrate buffer solution that pH value is 4.5, rotary evaporation,
The mixture of trehalose and Amoxicillin is obtained, suitable PVP K30 granulation is added, it is dry；
(b) potassium clavulanate is pulverized and sieved, is suspended in the dehydrated alcohol of beta-cyclodextrin, dry and remove ethyl alcohol, obtained
The potassium clavulanate of beta-cyclodextrin package；
(c) Amoxicillin after granulation is uniformly mixed with the potassium clavulanate that beta-cyclodextrin wraps up, add filler,
Disintegrating agent, mix lubricant, tabletting.
Embodiment 2:
Amoxicillin: 200g, trehalose: 10g, potassium clavulanate: 30g, beta-cyclodextrin: 15g, microcrystalline cellulose: 12g,
Sorbierite: 3g, crospovidone: 50g, sodium carboxymethyl starch: 50g, magnesium stearate: 1g.
The pH value of sodium citrate sodium buffer is 3, and the preparation method is the same as that of Example 1 for other.
Embodiment 3:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 100g, potassium clavulanate: 30g, beta-cyclodextrin: 45g, microcrystalline cellulose:
120g, sorbierite: 30g, crospovidone: 250g, sodium carboxymethyl starch: 250g, magnesium stearate: 10g.
The pH value of sodium citrate sodium buffer is 6, and the preparation method is the same as that of Example 1.
Embodiment 4
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, lactose: 40g, sorbierite:
10g, crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
The preparation method is the same as that of Example 1.
Embodiment 5
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 40g,
Sorbierite: 15g, crospovidone: 115g, sodium carboxymethyl starch: 115g.
The preparation method is the same as that of Example 1.
Comparative example 1
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 5g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, lactose: 40g
Sorbierite: 10g, crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
The preparation method is the same as that of Example 1.
Comparative example 2
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 40g, sorbierite: 8g is handed over
Join povidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 10g.
The preparation method is the same as that of Example 1.
Comparative example 3:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 50g,
Crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
The preparation method is the same as that of Example 1.
Comparative example 4:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 40g,
Lactose: 10g, crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
The preparation method is the same as that of Example 1.
Comparative example 5:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, beta-cyclodextrin: 30g, microcrystalline cellulose: 40g,
Sorbierite: 10g, crospovidone: 115g, sodium carboxymethyl starch: 115g, magnesium stearate: 5g.
Preparation process: (1) by Amoxicillin, potassium clavulanate, trehalose, beta-cyclodextrin, microcrystalline cellulose mixing；
(2) the uniformly mixed particle for obtaining step (1) is pumped into dry granulating machine, granulation；
(3) tabletting after disintegrating agent and lubricant total mix is added in the particle obtained to step (2).
Comparative example 6:
The prescription of 1000 dispersible tablets:
Amoxicillin: 200g, trehalose: 50g, potassium clavulanate: 30g, microcrystalline cellulose: 40g, sorbierite: 10g
Crospovidone: 130g, sodium carboxymethyl starch: 130g, magnesium stearate: 5g.
The preparation method is the same as that of Example 1.
A kind of comparative example 7: amoxicillin and clavulanate potassium dispersible tablet
Utimox 24.99kg, potassium clavulanate 3.57kg, microcrystalline cellulose 42kg, crospovidone
1.6kg, diatomite 0.16g, blueberry flavor 0.16kg, Sucralose 0.1kg.
Preparation process:
Various active constituents and auxiliary material are weighed by prescription, are sieved with 100 mesh sieve respectively, wherein 60 DEG C of dryings 2 of microcrystalline cellulose are small
When, various auxiliary materials are added to according to equal increments method in the mixed powder of Utimox and potassium clavulanate, in mixing machine
In after mixing, discharging carries out tabletting with oval special-shaped punch die to get amoxicillin and clavulanate potassium (7:1) dispersible tablet.
Test experiments
(1) investigation of appearance, disintegration time limited, sticking, moisture and tablet weight variation
The test result of 1 embodiment group of table
By accelerated test 6 months, from newly measuring above-mentioned result
The measurement result of embodiment each group after 2 accelerated test of table
| Appearance | Disintegration time limited (s)/25 DEG C | Moisture | |
| Embodiment 1 | It is unilateral bright and clean, it is white | 35 | 4.5 |
| Embodiment 2 | It is unilateral bright and clean, it is white | 36 | 4.9 |
| Embodiment 3 | It is unilateral bright and clean, it is white | 57 | 4.7 |
| Embodiment 4 | It is unilateral bright and clean, it is white | 46 | 4.7 |
| Embodiment 5 | It is unilateral bright and clean, it is white | 35 | 4.6 |
| Comparative example 1 | It is unilateral bright and clean, it is white | 97 | 6.3 |
| Comparative example 2 | It is unilateral bright and clean, it is white | 68 | 5.5 |
| Comparative example 3 | It is unilateral bright and clean, it is white | 66 | 6.1 |
| Comparative example 4 | It is unilateral bright and clean, it is white | 67 | 6.2 |
| Comparative example 5 | It is unilateral to have point, sliver, in faint yellow | 65 | 6.7 |
| Comparative example 6 | It is unilateral to have point, sliver, in faint yellow | 66 | 4.5 |
| Comparative example 7 | It is unilateral bright and clean, it is white | 89 | 8.8 |
By table 1 and 2 it can be seen that embodiment 1-4 all indicators are better than comparative example groups, it is unilateral bright and clean, in white
Color, disintegration time limited is within 50s.The index of embodiment 1 and embodiment 4 is better than embodiment 2 and 3.
The ratio in comparative example 1 is not protection scope of the present invention, and disintegration time limited extends, and is not achieved described
Technical effect.
Trehalose is not contained in comparative example 2, and technical effect of the invention is not achieved.
Comparative example 3 and comparative example 4 do not contain sorbierite, and moisture content is larger, and sticking phenomenon occurs.
5 preparation method of comparative example changes, and using the process of direct tablet compressing, dispersible tablet appearance is poor.
Comparative example 6 removes cyclodextrin, and the technical effect is also not achieved in appearance
A kind of amoxicillin and clavulanate potassium dispersible tablet of comparative example 7, the selection of preparation method and auxiliary material are different from
The present invention, technical effect are poor.
(2) dissolution rate, content, the investigation in relation to substance
2 amoxicillin and clavulanate potassium dispersible tablet Dissolution experiments result of table
Dissolution rate, content, related substance are investigated after accelerated test.Concrete outcome such as table 4
Amoxicillin and clavulanate potassium dispersible tablet Dissolution experiments result after 4 accelerated test of table
Embodiment group is that 90% or so, 5min or so is substantially completely molten in the dissolution of 2min it can be seen from table 3 and table 4
Out, other comparative examples are to be not achieved.
(3) test of mouthfeel degree
Test method: 20 volunteers, men and women is fifty-fifty, between 25-30 years old age.The dispersible tablet of 1 prescription to be tested is taken,
Every contains Amoxicillin (in terms of anhydride) 200mg, potassium clavulanate (in terms of clavulanic acid) 28.5mg, and merging fills 170ml
In the cup of water, water temperature is 25 DEG C or so, rocks cup after dispersible tablet is completely dispersed, Dispersion of Solute Matter is made uniformly to carry out product afterwards
It tastes, the test result of each prescription is shown in Table 3:
The sensory test of 5 prescription of table
| Prescription serial number | It is bad | Generally | It is good | Feature |
| Embodiment 1 | 0 | 0 | 20 | Micro-perfume, sweet tea do not have bilgy odour |
| Embodiment 2 | 0 | 2 | 18 | Micro-perfume, sweet tea do not have bilgy odour |
| Embodiment 3 | 0 | 3 | 17 | Micro-perfume, sweet tea do not have bilgy odour |
| Embodiment 4 | 0 | 1 | 19 | Micro-perfume, sweet tea do not have bilgy odour |
| Comparative example 1 | 3 | 9 | 8 | Micro-perfume, sweet tea do not have bilgy odour |
| Comparative example 2 | 5 | 10 | 5 | Micro-perfume, bilgy odour |
| Comparative example 3 | 8 | 12 | 0 | Bitter, bilgy odour |
| Comparative example 4 | 3 | 15 | 2 | Micro-perfume, sweet tea do not have bilgy odour |
| Comparative example 5 | 8 | 10 | 2 | Bitter, bilgy odour |
| Comparative example 6 | 13 | 7 | 0 | Micro-perfume, sweet tea do not have bilgy odour |
| Comparative example 7 | 2 | 18 | 0 | Micro-perfume, substantially without bilgy odour |
The sensory test of prescription after 6 accelerated test of table
Of the invention good in taste it can be seen from table 5 and table 6, the tolerance degree for being inferred to patient is higher, is suitble to clinic
Further genralrlization application.
Claims (10)
1. a kind of amoxicillin and clavulanate potassium dispersible tablet, which is characterized in that calculated with weight ratio, the dispersible tablet includes:
2. amoxicillin and clavulanate potassium dispersible tablet as described in claim 1, which is characterized in that it is calculated with weight ratio, it is described
Dispersible tablet include:
3. amoxicillin and clavulanate potassium dispersible tablet as described in claim 1, which is characterized in that it is calculated with weight ratio, it is described
Dispersible tablet include:
4. amoxicillin and clavulanate potassium dispersible tablet as described in claim 1, which is characterized in that the filler is cream
It is sugar, glucose, mannitol, dextran, microcrystalline cellulose, in one in sorbierite or a variety of；The disintegrating agent is crosslinking
One of povidone, pre-paying starch, dried starch, low-substituted hydroxypropyl cellulose, carboxyrnethyl starch sodium are a variety of；The profit
Lubrication prescription is one of magnesium stearate, sorbierite, calcium stearate, talcum powder or a variety of.
5. amoxicillin and clavulanate potassium dispersible tablet as described in claim 1, which is characterized in that the filler is selected from mountain
The mixture of the pure and mild milk-sugar mixture of pears or sorbierite and microcrystalline cellulose；The disintegrating agent is selected from crospovidone and carboxylic first
Base sodium starch mixture；The lubricant is selected from sorbierite or magnesium stearate.
6. amoxicillin and clavulanate potassium dispersible tablet as claimed in claim 5, which is characterized in that the sorbierite and crystallite
Cellulose amount ratio is 1:1-8, preferably 1:4.
7. amoxicillin and clavulanate potassium dispersible tablet as claimed in claim 5, which is characterized in that the sorbierite: lactose
Weight consumption ratio is 1:1-8, preferably 1:4.
8. a kind of method for preparing amoxicillin and clavulanate potassium dispersible tablet, it is characterised in that: the preparation method comprises the following steps:
(a) suitable Amoxicillin and trehalose are dissolved in sodium citrate buffer solution, rotary evaporation obtains trehalose and A Mo
Suitable adhesive granulation is added in the mixture in XiLin, dry；
(b) potassium clavulanate is pulverized and sieved, is suspended in the dehydrated alcohol of beta-cyclodextrin, dry and remove ethyl alcohol, obtain β-ring
The potassium clavulanate of dextrin package；
(c) Amoxicillin after granulation is uniformly mixed with the potassium clavulanate that beta-cyclodextrin wraps up, adds filler, disintegration
Agent, mix lubricant, tabletting.
9. the method for claim 7, which is characterized in that the adhesive is starch slurry, hydroxypropyl methylcellulose, poly- dimension
One of ketone K30 or a variety of.
10. the method for claim 7, which is characterized in that the pH value of the sodium citrate buffer solution is 3-6, preferably
PH value is 4.5.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110051637A (en) * | 2019-05-21 | 2019-07-26 | 葵花药业集团北京药物研究院有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
| CN112190561A (en) * | 2020-10-30 | 2021-01-08 | 四川制药制剂有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
| CN115364057A (en) * | 2021-05-20 | 2022-11-22 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083129A2 (en) * | 2001-04-12 | 2002-10-24 | Sandoz Gmbh | Pharmaceutical composition comprising clavulanic acid |
| CN1698604A (en) * | 2005-04-30 | 2005-11-23 | 南京师范大学 | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof |
| CN101502511A (en) * | 2008-09-09 | 2009-08-12 | 山东淄博新达制药有限公司 | Amoxicillin/clavulanate potassium tablet and preparation method thereof |
| CN103417503A (en) * | 2013-08-23 | 2013-12-04 | 南京正宽医药科技有限公司 | Amoxicillin potassium clavulanate tablet and preparation technology thereof |
| US20150245995A1 (en) * | 2014-03-03 | 2015-09-03 | Sandoz Ag | Stable Quick Dissolving Dosage Form Comprising Amoxicillin and Clavulanic Acid |
-
2017
- 2017-07-13 CN CN201710569445.5A patent/CN109248150B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083129A2 (en) * | 2001-04-12 | 2002-10-24 | Sandoz Gmbh | Pharmaceutical composition comprising clavulanic acid |
| CN1698604A (en) * | 2005-04-30 | 2005-11-23 | 南京师范大学 | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof |
| CN101502511A (en) * | 2008-09-09 | 2009-08-12 | 山东淄博新达制药有限公司 | Amoxicillin/clavulanate potassium tablet and preparation method thereof |
| CN103417503A (en) * | 2013-08-23 | 2013-12-04 | 南京正宽医药科技有限公司 | Amoxicillin potassium clavulanate tablet and preparation technology thereof |
| US20150245995A1 (en) * | 2014-03-03 | 2015-09-03 | Sandoz Ag | Stable Quick Dissolving Dosage Form Comprising Amoxicillin and Clavulanic Acid |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051637A (en) * | 2019-05-21 | 2019-07-26 | 葵花药业集团北京药物研究院有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
| CN112190561A (en) * | 2020-10-30 | 2021-01-08 | 四川制药制剂有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
| CN112190561B (en) * | 2020-10-30 | 2022-02-01 | 四川制药制剂有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
| CN115364057A (en) * | 2021-05-20 | 2022-11-22 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
| CN115364057B (en) * | 2021-05-20 | 2024-01-30 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
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