CN102228448A - Cefuroxime axetil tablet and direct all-powder compression method thereof - Google Patents

Cefuroxime axetil tablet and direct all-powder compression method thereof Download PDF

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CN102228448A
CN102228448A CN2011101709789A CN201110170978A CN102228448A CN 102228448 A CN102228448 A CN 102228448A CN 2011101709789 A CN2011101709789 A CN 2011101709789A CN 201110170978 A CN201110170978 A CN 201110170978A CN 102228448 A CN102228448 A CN 102228448A
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cefuroxime axetil
sucrose
mannitol
ion exchange
exchange resin
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CN102228448B (en
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邓宝军
黄艳
曾环想
胡瑞祥
罗炳锋
朱良
曾玮
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Sinopharm Zhijun Shenzhen Pharmaceutical Co Ltd
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Shenzhen Zhijun Pharmaceutical Co Ltd
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Priority to PCT/CN2011/078464 priority patent/WO2012174784A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Abstract

The invention discloses a cefuroxime axetil tablet and a direct all-powder compression method thereof, wherein the technical problem to be solved is to increase the quality of cefuroxime axetil tablet and decrease manufacturing cost. The weight percentage ingredients of the cefuroxime axetil tablet of the invention are as follows: 45-65% of cefuroxime axetil, 4-10% of ion exchange resin, 3-8% of sodium cross-linked carboxymethyl cellulose, 3-8% of sucrose fatty acid ester and 0.5-1.5% of aerosol. The compression method comprises the steps of: sieving, mixing and compressing. Compared with the prior art, the method of the invention directly compresses after uniformly mixing cefuroxime axetil amorphous powder with auxiliary materials, wherein the isomer E, isomer Delta 3 and impurity content of the cefuroxime axetil tablet are lower, and the dissolution rate is higher; the problems of thermal decomposition and oxidation, extrusion and denaturation of the medicine while being wetted are avoided; the medicine stability is increased and the product quality is ensured; simultaneously, the cefuroxime axetil tablet has a higher production efficiency and a lower manufacturing cost, which is suitable for industrialized production application.

Description

Cefuroxime axetil tablets and direct compression of full-powder method thereof
Technical field
The present invention relates to a kind of antibiotics oral solid formulation and preparation method thereof, but the direct compression of full-powder method of particularly a kind of cefuroxime axetil tablets and industrial applications thereof.
Background technology
Tablet is the most widely used a kind of dosage form of present pharmaceutical preparation, and its preparation method can be divided into common granulating tabletting process and direct compression of full-powder method two big classes.Common granulating tabletting process can be divided into two kinds of wet granule compression tablet method and compressing dry granulations again according to the particulate technology difference of preparation.The direct compression of full-powder method is meant behind the powder of medicine and the suitable adjuvant mix homogeneously, without system granule (wet granular or dried granule) and the method for direct compression.
Current, the tablet manufacturing of China is still extensive with common granulating tabletting process, and the direct compression of full-powder method is used less.The direct compression of full-powder method is different from common granulating tabletting process, and the material that its requirement is used for tabletting all is pulverous fine powder, and material compressibility and mobile quality are with the quality of decision final products.Because the flowability of most drug powder and the Technology requirement that compressibility all can not satisfy direct compression of full-powder, and the tablet machine of most of manufacturing enterprises does not have good powder device, dust arrester and the prepressing device of raising, be difficult to guarantee carrying out smoothly of direct compression of full-powder process, so the application of the suitability for industrialized production of direct compression of full-powder method is subjected to many restrictions.
Compare with common granulating tabletting process, the direct compression of full-powder method has tangible technical advantage and cost advantage.At first, the direct compression of full-powder method has been avoided the influence to tablet and technology of heating and moisture.In actual production; run into the medicine of some unstable chemcial property through regular meeting; esters, amide-type medicine as facile hydrolysis; the phenolic hydroxyl group class medicine of easy oxidation, vitamin C etc.; these medicines tend to take place hydrolysis in common wet granule compression tablet method; or it is destroyed to be heated in the particle drying process, or because complex process causes medicine to see photolysis etc.For these problems, the direct compression of full-powder method can solve.The direct compression of full-powder method need not to granulate, drying-free, thus can protect the quality stability of medicine effectively, avoid it because the various unstable factors that wet granulation causes, thereby guarantee the quality of product.Simultaneously, the production technology of direct compression of full-powder method is simple, shortens the production cycle, enhance productivity, and the energy-and time-economizing, thus can reduce production cost of products.
The active ingredient of cefuroxime axetil tablets is a cefuroxime, it is oral in gastrointestinal absorption enters body, under the esterase effect, be hydrolyzed to cefuroxime rapidly, by combining with one or more penicillin-binding proteins (PBPs), the cell wall that suppresses the antibacterial somatoblast is synthetic, thus the performance antibacterial action.
CEFUROXIME AXETIL is the acetyl triethyl of cefuroxime, belongs to prodrug, after the oral absorption in vivo hydrolysis discharge cefuroxime and bring into play its antibacterial activity, gram positive coccus, gram-negative bacteria and escherichia coli etc. are had strong antibacterial activity.Cefuroxime has broad spectrum antibiotic activity, and is lower to Toxicity of Kidney, is widely used in the treatment of respiratory tract infection, urinary system infection, skin and soft tissue infection etc. clinically.
CEFUROXIME AXETIL is to make crystallization product by cefuroxime acid through three steps of over-churning, hydrolysis, crystallization, the unformed powder that makes after spray-dried again, and flowability is relatively poor; Odorless almost, bitter in the mouth; Easily molten in acetone, in chloroform, dissolve, molten at methanol or ethanol part omitted, slightly soluble in ether, insoluble in water.
CEFUROXIME AXETIL belongs to acyl Ammonia antibiotic in the β, to damp and hot instability.Because CEFUROXIME AXETIL is unsettled unformed powder, and water insoluble, the quality stability of its tablet and bioavailability are subjected to the influence of pharmaceutical preparation technology bigger, document (" Chinese Medicine guide " calendar year 2001; " China Dispensary " 2008) think that the tablet stability of compressing dry granulation gained will be significantly better than the wet granule compression tablet person, but the production efficiency of dry granulation is lower, and cost of goods manufactured is higher.
Summary of the invention
The purpose of this invention is to provide a kind of cefuroxime axetil tablets and direct compression of full-powder method thereof, the technical problem that solve is to adopt the direct compression of full-powder method to improve the product quality of cefuroxime axetil tablets, and reduces the manufacturing cost of product.
The present invention is by the following technical solutions: a kind of cefuroxime axetil tablets, and the percentage by weight component that described cefuroxime axetil tablets comprises is: CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%; Described CEFUROXIME AXETIL be (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester; Described ion exchange resin styrene ion exchange resin, methacrylic acid ion exchange resin; In described sucrose fatty acid ester sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 more than one.
Cefuroxime axetil tablets of the present invention contains the percentage by weight component: starch greater than 0 to 30%, sucrose greater than 0 to 25%, mannitol is greater than 0 to 30%; Described starch is with a kind of of pregelatinized Starch, partially pregelatinized starch or two kinds; Described sucrose is with a kind of in white sugar, caster sugar, the meticulous caster sugar or two kinds; In described mannitol crystallized mannitol, spray drying mannitol, the melt granulation mannitol more than one.
Cefuroxime axetil tablets of the present invention is a Film coated tablets, in the Opadry coating premix material of the coating material of cefuroxime axetil tablets, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide more than one, coating material is 2%～3.5% of a label weight.
The percentage by weight component that the label of cefuroxime axetil tablets of the present invention comprises is: cefuroxime axetil tablets CEFUROXIME AXETIL 45%～60%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 5～25%, sucrose 5～20%, mannitol 5～25%.
The percentage by weight component that the label of cefuroxime axetil tablets of the present invention comprises is: CEFUROXIME AXETIL 50%～55%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～.1.5%, starch 10～20%, sucrose 10～15%, mannitol 10～20%.
A kind of direct compression of full-powder method of cefuroxime axetil tablets may further comprise the steps: one, CEFUROXIME AXETIL, ion exchange resin, cross-linking sodium carboxymethyl cellulose, sucrose fatty acid ester, micropowder silica gel are sieved respectively, granularity is 30～80 orders; Two, press the percentage by weight of label, with CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, starch 0～30%, sucrose 0～25%, mannitol 0～30%, micropowder silica gel 0.5～1.5%, rotating speed with 10～20 rev/mins, mixed 15～45 minutes, and obtained intermediate; Described CEFUROXIME AXETIL be (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester; Described ion exchange resin styrene ion exchange resin, methacrylic acid ion exchange resin; In described sucrose fatty acid ester sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 more than one; Three, intermediate is carried out tabletting by prior art, obtain cefuroxime axetil tablets.
Method of the present invention by weight percentage, with percentage by weight component starch greater than 0 to 30%, sucrose greater than 0 to 25% and/or mannitol greater than 0 to 30%, CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, starch 0～30%, sucrose 0～25%, mannitol 0～30%, micropowder silica gel 0.5～1.5% with step 2, rotating speed with 10～20 rev/mins, mixed 15～45 minutes, and obtained intermediate; Described starch is with a kind of of pregelatinized Starch, partially pregelatinized starch or two kinds; Described sucrose is with a kind of in white sugar, caster sugar, the meticulous caster sugar or two kinds; In described mannitol crystallized mannitol, spray drying mannitol, the melt granulation mannitol more than one.
Method of the present invention is to described CEFUROXIME AXETIL coating tablets, in coating material Opadry coating premix material, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide more than one, coating material is 2～3.5% of a cefuroxime axetil tablets label weight.
The percentage by weight component that the label of the described cefuroxime axetil tablets of method of the present invention comprises is: CEFUROXIME AXETIL 45%～60%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 5～25%, sucrose 5～20%, mannitol 5～25%.
The percentage by weight component that the label of the described cefuroxime axetil tablets of method of the present invention comprises is: CEFUROXIME AXETIL 50%～55%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～.1.5%, starch 10～20%, sucrose 10～15%, mannitol 10～20%.
The present invention compared with prior art behind unformed powder of CEFUROXIME AXETIL and adjuvant mix homogeneously, directly carries out tabletting, the E isomer of cefuroxime axetil tablets, Δ 3Isomer and impurity content are lower, dissolution is higher, product quality is better, the direct compression of full-powder method of cefuroxime axetil tablets has avoided medicine to meet the problem of damp and hot decomposing oxidation, extruding degeneration, improve medicine stability, guarantee product quality, simultaneously, the production efficiency of cefuroxime axetil tablets is higher, manufacturing cost is lower, comparing with existing common granulating tabletting process from aspects such as production cycle, production operation complexity, production efficiency, production environmental protection, administrative expenses, power costs all has very large superiority, can adapt to industrialized great production and use.
Description of drawings
Fig. 1 is the common pelletizing press sheet process chart of prior art.
Fig. 2 is a direct compression of full-powder method flow diagram of the present invention.
The specific embodiment
Below in conjunction with drawings and Examples the present invention is described in further detail.Cefuroxime axetil tablets of the present invention is a Film coated tablets, be that label (plain sheet) is coated with coating material, the percentage by weight component of label is: CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 0～30%, sucrose 0～25%, mannitol 0～30%.Coating material is 2%～3.5% of a label weight.
The preferred percentage by weight component of described label is: CEFUROXIME AXETIL 45%～60%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 5～25%, sucrose 5～20%, mannitol 5～25%.
The further preferred percentage by weight component of described label is: CEFUROXIME AXETIL 50%～55%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 10～20%, sucrose 10～15%, mannitol 10～20%.
Described CEFUROXIME AXETIL is (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester, be white or off-white powder, bitter in the mouth, insoluble in water, detect by Chinese Pharmacopoeia version appendix in 2010 IXD crystallinity inspection technique, there are not extinction position and birefringent phenomenon.
Described ion exchange resin is selected styrene ion exchange resin, methacrylic acid ion exchange resin for use.Styrene ion exchange resin is the copolymer of styrene and divinylbenzene, and methacrylic acid ion exchange resin is the copolymer of methacrylic acid and divinylbenzene.
Described sucrose fatty acid ester is selected any or the mixing more than two kinds in sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 for use.
Described starch is selected the mixing of any or two kinds of pregelatinized Starch, partially pregelatinized starch for use.
Described sucrose is selected any or the mixing more than two kinds in white sugar, caster sugar, the meticulous caster sugar for use.
Described mannitol is selected any or the mixing more than two kinds in crystallized mannitol, spray drying mannitol, the melt granulation mannitol for use.
Described coating material is selected any or the mixing more than two kinds in the premix material of Opadry coating, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide for use.
As shown in Figure 2, cefuroxime axetil tablets direct compression of full-powder method of the present invention may further comprise the steps:
One, pretreatment: CEFUROXIME AXETIL, ion exchange resin, cross-linking sodium carboxymethyl cellulose, sucrose fatty acid ester, starch, sucrose, mannitol are sieved respectively (adopt YK160 type oscillating granulator, produce the Baoji), granularity is 30～80 orders, and is standby.
Two, press the percentage by weight of label, with CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, starch 0～30%, sucrose 0～25%, mannitol 0～30%, micropowder silica gel 0.5～1.5%, put into mixer and (adopt SDH-50 type mixer, Jiangyin rarity produces), rotating speed with 10～20 rev/mins, mixed 15～45 minutes, mix homogeneously obtains intermediate.
Described CEFUROXIME AXETIL is (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester, be white or off-white powder, bitter in the mouth, insoluble in water, detect by Chinese Pharmacopoeia version appendix in 2010 IXD crystallinity inspection technique, there are not extinction position and birefringent phenomenon.
Described ion exchange resin is selected styrene ion exchange resin, methacrylic acid ion exchange resin for use.Styrene ion exchange resin is the copolymer of styrene and divinylbenzene, and methacrylic acid ion exchange resin is the copolymer of methacrylic acid and divinylbenzene.
Described sucrose fatty acid ester is selected any or the mixing more than two kinds in sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 for use.
Described starch is selected the mixing of any or two kinds of pregelatinized Starch, partially pregelatinized starch for use.
Described sucrose is selected any or the mixing more than two kinds in white sugar, caster sugar, the meticulous caster sugar for use.
Described mannitol is selected any or the mixing more than two kinds in crystallized mannitol, spray drying mannitol, the melt granulation mannitol for use.
Three, intermediate is checked the cefuroxime content of described intermediate by Chinese Pharmacopoeia version in 2010, determine that according to cefuroxime content in the intermediate sheet is heavy, carry out tabletting (adopt P2020 type tablet machine, German Fitow produces), obtain plain sheet by prior art.
Four, plain sheet is checked the dissolution and the tablet weight variation of described plain sheet by Chinese Pharmacopoeia version in 2010, after the project of check meets Chinese Pharmacopoeia version in 2010, with plain sheet as label, by coating material is 2～3.5% of label weight, carry out film coating with prior art and (adopt BGB-10F type film coating, produce in Wenzhou, Zhejiang), obtain coated tablet.
Described coating material is selected any or the mixing more than two kinds in the premix material of Opadry coating, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide for use.
Five, coated tablet is checked cefuroxime content, E isomer, the Δ of described coated tablet by Chinese Pharmacopoeia version in 2010 3Isomer and impurity (E isomer, Δ 3Isomer and impurity general name related substance), and the dissolution of coated tablet, the project of check is packed (adopt CVC plastic-aluminum/aluminum aluminum blister packaging machine, the Taiwan emperor will produce) by prior art after meeting Chinese Pharmacopoeia version in 2010, promptly gets the cefuroxime axetil tablets finished product.
Embodiment 1: the product prescription:
Figure BDA0000070611290000081
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, mannitol are put into mixer, mix with 10 rev/mins rotating speeds, and the time is 45 minutes, promptly get intermediate.3. after intermediate being checked content, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Above-mentioned production process is operated according to Chinese medicine GMP standard, each production equipment must clean before using, the device fabrication operation is carried out according to the SOP rule of operation, also should in time carry out equipment cleaning cleaning after producing end, produce and be meant that device fabrication operating time and equipment clean the cleaning time sum man-hour.The plain sheet actual measurement sheet that detects this batch product by two appendix I of Chinese Pharmacopoeia version in 2010 rules of preparations is heavy, calculates 20 the heavy and tablet weight variation of average sheet; Press two cefuroxime content and related substances that detect this batch product of Chinese Pharmacopoeia version in 2010, the assay of Chinese Pharmacopoeia regulation cefuroxime axetil tablets is meant the percentage composition of medicine labelled amount, and cefuroxime axetil tablets of the present invention contains CEFUROXIME AXETIL by cefuroxime (C 16H 16N 4O 8S) calculate, should be 90.0%～110.0% of labelled amount, related substance should be less than 4.5%.Press two dissolutions that detect this batch product of Chinese Pharmacopoeia version in 2010, Chinese Pharmacopoeia regulation cefuroxime axetil tablets should be respectively greater than 60% with greater than 75% at the dissolution of 15 minutes and 45 minutes.Press two note on the use regulations of Chinese Pharmacopoeia version in 2010, content and determination of dissolution rate result might surpass 100%, at this moment mean the numerical value that may reach when measuring with this analysis method, it is not true amount for the limit of Chinese Pharmacopoeia regulation or the deviation of permission.
The production of this batch product has been saved granulation, drying and has always been mixed 3 operations, and production is shorter man-hour, and tablet weight variation is less, related substance is lower, and dissolution is higher, shows that manufacturing cost of the present invention is lower, and product quality is better.Experimental result sees Table 1.
The production man-hour of table 1 embodiment 1 and the tablet weight variation of sample, content, related substance and dissolution result
Embodiment 2: the product prescription:
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, pregelatinized Starch, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Cross-linking sodium carboxymethyl cellulose is crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, pregelatinized Starch, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 13 rev/mins mixes, time is 40 minutes, promptly gets intermediate.3. after intermediate being checked content, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 2.
The production man-hour of table 2 embodiment 2 and the tablet weight variation of sample, content, related substance and dissolution result
Embodiment 3: the product prescription:
Figure BDA0000070611290000112
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Meticulous caster sugar, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, meticulous caster sugar, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 15 rev/mins mixes, time is 35 minutes, promptly gets intermediate.3. after intermediate being checked content, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 3.
The production man-hour of table 3 embodiment 3 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000121
Embodiment 4: the product prescription:
Figure BDA0000070611290000122
Figure BDA0000070611290000131
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, mannitol, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 15 rev/mins mixes, time is 30 minutes, promptly gets intermediate.3. with intermediate after the assay was approved, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 4.
The production man-hour of table 4 embodiment 4 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000132
Embodiment 5: the product prescription:
Figure BDA0000070611290000133
Figure BDA0000070611290000141
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, meticulous caster sugar, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, meticulous caster sugar, mannitol, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 17 rev/mins mixes, time is 25 minutes, promptly gets intermediate.3. with intermediate after the assay was approved, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 5.
The production man-hour of table 5 embodiment 5 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000142
Figure BDA0000070611290000151
Embodiment 6: the product prescription:
Figure BDA0000070611290000152
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, mannitol, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 20 rev/mins mixes, time is 20 minutes, promptly gets intermediate.3. with intermediate after the assay was approved, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 6.
The production man-hour of table 6 embodiment 6 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000161
Embodiment 7: the product prescription:
Figure BDA0000070611290000162
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, meticulous caster sugar, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, mannitol, meticulous caster sugar, partially pregelatinized starch, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 20 rev/mins mixes, time is 20 minutes, promptly gets intermediate.3. with intermediate after the assay was approved, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 7.
The production man-hour of table 7 embodiment 7 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000171
Embodiment 8: the product prescription:
Figure BDA0000070611290000172
Figure BDA0000070611290000181
Preparation technology:
1. pretreatment: 80 mesh sieves are crossed in CEFUROXIME AXETIL, pregelatinized Starch, sucrose fatty acid ester, ion exchange resin, micropowder silica gel; Mannitol, meticulous caster sugar, cross-linking sodium carboxymethyl cellulose are crossed 40 mesh sieves.2. mixer is put in the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, mannitol, meticulous caster sugar, pregelatinized Starch, sucrose fatty acid ester, ion exchange resin, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, rotating speed with 15 rev/mins mixes, time is 30 minutes, promptly gets intermediate.3. with intermediate after the assay was approved, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.4. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.5. coated tablet is packed after the assay was approved, gets product.
Experimental result sees Table 8.
The production man-hour of table 8 embodiment 8 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000182
Comparative Examples 1
Chinese patent CN101874791A discloses a kind of cefuroxime axetil tablet and preparation method thereof, and we have carried out comparative study with reference to the embodiment in its description 1, and are specific as follows:
The product prescription:
Preparation technology:
1. pretreatment: microcrystalline Cellulose is crossed 60 mesh sieves, and carboxymethylstach sodium, calcium carbonate are crossed 80 mesh sieves.2. the carboxymethylstach sodium of CEFUROXIME AXETIL, microcrystalline Cellulose, 1/2 amount, crospolyvinylpyrrolidone, the calcium carbonate of 1/2 amount are put into mixer, mix with 10 rev/mins rotating speeds, the time is 45 minutes, mix homogeneously.3. the supplementary material with above-mentioned mixing adds the mixed liquor that includes 5% polyvinylpyrrolidone and 3% sodium lauryl sulphate, stirs and makes suitable soft material, granulates with 20 mesh sieves.4. with above-mentioned wet granular hot-air oven, dried 120 minutes down, carry out granulate with oscillating granulator then, promptly get dried granule at 40～55 ℃.5. above-mentioned dried granule is added remaining carboxymethylstach sodium, crospolyvinylpyrrolidone, magnesium stearate, white carbon, place in the mixer, mix with 15 rev/mins rotating speeds, the time is 10 minutes, and mix homogeneously promptly gets intermediate.6. after intermediate being checked content, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.6. plain sheet is wrapped after the assay was approved routinely the operation coating of film-coat, coating solution sprays at a slow speed, 35～40 ℃ of canyon dryings.Stop hydrojet when the slice, thin piece weightening finish reaches 2.8～3.4%, blowing is drying to obtain coated tablet.7. coated tablet is packed after the assay was approved, gets product.
The production of this batch product has increased granulation, drying and has always mixed 3 operations, and production is longer man-hour, and related substance is higher, and medicament contg and dissolution are lower, show that manufacturing cost of the present invention is higher, and product quality is relatively poor.Experimental result sees Table 9.
The production man-hour of table 9 Comparative Examples 1 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000201
Comparative Examples 2
" Chinese Medicine guide " calendar year 2001 has been reported the preparation technology and the stability study thereof of cefuroxime axetil tablets, and we have carried out comparative study by the dry granulation technology in its document, and are specific as follows:
The product prescription:
Figure BDA0000070611290000202
Preparation technology:
1. pretreatment: CEFUROXIME AXETIL, microcrystalline Cellulose, carboxymethylstach sodium, sodium lauryl sulphate are crossed 80 mesh sieves.2. the CEFUROXIME AXETIL of the above-mentioned recipe quantity of weighing, microcrystalline Cellulose, carboxymethylstach sodium, sodium lauryl sulphate are put into mixer, mix with 10 rev/mins rotating speeds, and the time is 45 minutes, mix homogeneously.3. above-mentioned mixing supplementary material is carried out the dry method extruding with the dry granulation machine and granulate, with 20 mesh sieve granulate, fine powder returns proceeds dry method extruding granulation, and circulation repeatedly promptly gets dried granule through granulate repeatedly.4. above-mentioned dried granule is added magnesium stearate, the Pulvis Talci of recipe quantity, mix with 10 rev/mins rotating speeds, the time is 15 minutes, and mix homogeneously promptly gets intermediate.5. after intermediate being checked content, determine that according to the intermediate assay sheet heavily carries out tabletting, promptly gets plain sheet.6. plain sheet is carried out coating after the assay was approved, promptly get coated tablet.7. coated tablet is packed after the assay was approved, gets product.
The production of this batch product is compared with the present invention has increased dry granulation and total mixed 2 operations, and production is longer man-hour, and related substance is higher, and medicament contg and dissolution are lower, show that manufacturing cost of the present invention is higher, and product quality is relatively poor.Experimental result sees Table 10.
The production man-hour of table 10 Comparative Examples 2 and the tablet weight variation of sample, content, related substance and dissolution result
Figure BDA0000070611290000212
The present invention adopts ion exchange resin to improve the flowability and the compressibility of CEFUROXIME AXETIL tablet recipe supplementary material powder, thereby can realize direct compression of full-powder.Ion exchange resin has good flowability and compressibility.We adopt laser particle analyzer and funnel method to measuring the granularity and the angle of repose of ion exchange resin, wherein mean diameter (the d of Amberlite IRP-64, Amberlite IRP-88, Amberlite IRP-69 0.5) be respectively 52.95 μ m, 57.33 μ m and 62.31 μ m, belong to the fine powder of Chinese Pharmacopoeia version in 2010 regulation; Be respectively 24.3 °, 28.9 ° and 27.7 ° average angle of repose, and show that all less than 30 ° its flowability is all fine the angle of repose of three kinds of ion exchange resin; Average apparent density is respectively 0.544g/cm 3, 0.692g/cm 3, 0.663g/cm 3, average tap density is respectively 0.720g/cm 3, 0.852g/cm 3, 0.817/cm 3, the bulk density of three kinds of ion exchange resin is all greater than 0.5g/cm 3, belong to " matter is heavy " powder body, and its good fluidity.
The present invention adopts ion exchange resin to improve the disintegrate dissolving out capability of cefuroxime axetil tablets in aqueous solution or gastro-intestinal Fluid.Because ion exchange resin contains a large amount of hydrophilic groups, has stronger water absorbing capacity, contacting with aqueous solution is imbibition.The balance water absorbent rate that we measure ion exchange resin Amberlite IRP-64, Amberlite IRP-69, Amberlite IRP-88 resin is respectively 1.447g/g (dried resin), 1.354g/g (dried resin) and 1.651g/g (dried resin).When the ion conversion in the resin, as cationic resin by H +Type transfers Na to +Type, resin anion (R.A.) is by Cl -Type transfers OH to -Type all expands because of ionic diameter increases, and increases the volume of ion exchange resin.Mean diameter (d after the Amberlite IRP-69 imbibition 0.5) to increase about 10 μ m.After the ion exchange resin suction certain swelling degree is arranged all, can press, cefuroxime axetil tablets is very easily expanded in aqueous solution or gastro-intestinal Fluid disperse by producing internal penetration, disintegrate stripping rapidly, thus can guarantee the clinical efficacy of cefuroxime axetil tablets.
The present invention adopts sucrose fatty acid ester to improve the disintegrate dissolving out capability of cefuroxime axetil tablets in aqueous solution or gastro-intestinal Fluid.Sucrose fatty acid ester has surface of good activating agent function, and insoluble drug is had good dispersion hydrotropy effect, can improve the hydrophobicity of cefuroxime axetil tablets, promotes disintegrate and stripping.
Cefuroxime axetil tablets of the present invention adopts thin membrane coated tablet, can shelter the bitterness of CEFUROXIME AXETIL, and helps the patient and swallow smooth and easyly, improves the compliance of patient's medication.
The lean management emphasis of modern enterprise in pharmaceutical production is production efficiency (time factor), product cost (benefit factor) and quality assurance (qualitative factor).The core connotation of lean management is the manpower with still less, with equipment still less, uses less time, uses less space, does more thing, when satisfied product and service are provided for client, waste is dropped to minimum level.Lean management will drop into exactly less, few consumption of natural resource, take time less, especially will reduce the input of non-renewable resources and expends, thereby create high-quality and high benefit.
The sharpest edges of cefuroxime axetil tablets of the present invention and direct compression of full-powder thereof are its economy.Angle from lean management, production process reduces, produce and shorten man-hour, reduce manpower, minimizing equipment (reduce investment, cut down the consumption of energy), in shorter time and littler space production more products, thereby the raising production efficiency of products reduces cost of goods manufactured, can produce the social benefit of " energy-saving and emission-reduction " simultaneously.
As shown in Figure 1, the common granulating tabletting process of prior art is produced cefuroxime axetil tablets, need earlier drug powder to be mixed, carry out wet granulation and particle drying then, perhaps carry out dry granulation and fine powder and circulate extruding repeatedly repeatedly, behind the granulate that sieves, must do granule, the more dried granule of gained and lubricant, fluidizer etc. be carried out always mixing, promptly get intermediate.After intermediate checked content, determine that according to the intermediate assay sheet heavily carries out tabletting.The common granulating tabletting process of prior art is produced in the process of cefuroxime axetil tablets, and the granulating process step restricts the speed of producing and influences product quality.The production operation of granulating process is loaded down with trivial details, and it is long to produce man-hour, and production efficiency is lower, take more manually, granulation operating process dust is bigger, influences health of operators.In addition, the influence factor of common wet granule compression tablet technology is more, for example (,) binder concn, binding agent add mode, granulation time (endpoint), water content control or the like often the workman rely on experience, the poor reproducibility of product quality; The influence factor of same common dry granulation tablet forming technique is also a lot, for example the supplementary material compressibility, do extruding force, sheet extrusion thickness, thin slice and smash intensity, cooling water temperature, fine powder and push number of times or the like repeatedly and often rely on workman's experience, the poor reproducibility of product quality.
As shown in Figure 2; cefuroxime axetil tablets direct compression of full-powder method of the present invention; need not to carry out wet granulation or dry granulation, granulate sieves and fine powder is carried out repetition extrusion process; directly mixing of materials is got final product tabletting after evenly; can save the granulation link, reduce dust, shorten life cycle of the product; enhance productivity, reduce production costs.
Cefuroxime axetil tablets of the present invention and direct compression of full-powder method thereof are with behind unformed powder of CEFUROXIME AXETIL and the adjuvant mix homogeneously, can directly carry out the preparation method of tabletting without granulate (wet granulation or dry granulation).Because CEFUROXIME AXETIL belongs to acyl Ammonia antibiotic in the β, to damp and hot instability, therefore the advantage of direct compression of full-powder method of the present invention is: 1, without processes such as wet method or dry granulation, oven dry, shortened the production cycle, reduce energy resource consumption, save production cost.2, avoid medicine to meet the problem of damp and hot decomposing oxidation, extruding degeneration, improved medicine stability, guaranteed product quality.

Claims (10)

1. cefuroxime axetil tablets, it is characterized in that: the percentage by weight component that described cefuroxime axetil tablets comprises is: CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%; Described CEFUROXIME AXETIL be (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester; Described ion exchange resin styrene ion exchange resin, methacrylic acid ion exchange resin; In described sucrose fatty acid ester sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 more than one.
2. cefuroxime axetil tablets according to claim 1 is characterized in that: described cefuroxime axetil tablets contains the percentage by weight component: starch greater than 0 to 30%, sucrose greater than 0 to 25%, mannitol is greater than 0 to 30%; Described starch is with a kind of of pregelatinized Starch, partially pregelatinized starch or two kinds; Described sucrose is with a kind of in white sugar, caster sugar, the meticulous caster sugar or two kinds; In described mannitol crystallized mannitol, spray drying mannitol, the melt granulation mannitol more than one.
3. cefuroxime axetil tablets according to claim 2, it is characterized in that: described cefuroxime axetil tablets is a Film coated tablets, in the Opadry coating premix material of the coating material of cefuroxime axetil tablets, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide more than one, coating material is 2%～3.5% of a label weight.
4. cefuroxime axetil tablets according to claim 3 is characterized in that: the percentage by weight component that the label of described cefuroxime axetil tablets comprises is: cefuroxime axetil tablets CEFUROXIME AXETIL 45%～60%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 5～25%, sucrose 5～20%, mannitol 5～25%.
5. cefuroxime axetil tablets according to claim 4 is characterized in that: the percentage by weight component that the label of described cefuroxime axetil tablets comprises is: CEFUROXIME AXETIL 50%～55%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～.1.5%, starch 10～20%, sucrose 10～15%, mannitol 10～20%.
6. the direct compression of full-powder method of a cefuroxime axetil tablets, may further comprise the steps: one, CEFUROXIME AXETIL, ion exchange resin, cross-linking sodium carboxymethyl cellulose, sucrose fatty acid ester, micropowder silica gel are sieved respectively, granularity is 30～80 orders; Two, press the percentage by weight of label, with CEFUROXIME AXETIL 45%～65%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, starch 0～30%, sucrose 0～25%, mannitol 0～30%, micropowder silica gel 0.5～1.5%, rotating speed with 10～20 rev/mins, mixed 15～45 minutes, and obtained intermediate; Described CEFUROXIME AXETIL be (6R, 7R)-7-[2-furyl (methoxyimino) acetylamino]-3-carbamyl oxygen methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, (1RS)-1-acetoxyl group ethyl ester; Described ion exchange resin styrene ion exchange resin, methacrylic acid ion exchange resin; In described sucrose fatty acid ester sucrose stearate, sucrose palmitate, the Surfhope SE Cosme C 1216 more than one; Three, intermediate is carried out tabletting by prior art, obtain cefuroxime axetil tablets.
7. the direct compression of full-powder method of cefuroxime axetil tablets according to claim 6, it is characterized in that: by weight percentage, with percentage by weight component starch greater than 0 to 30%, sucrose greater than 0 to 25% and/or mannitol greater than 0 to 30%, CEFUROXIME AXETIL 45%～65% with step 2, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, starch 0～30%, sucrose 0～25%, mannitol 0～30%, micropowder silica gel 0.5～1.5%, rotating speed with 10～20 rev/mins, mixed 15～45 minutes, and obtained intermediate; Described starch is with a kind of of pregelatinized Starch, partially pregelatinized starch or two kinds; Described sucrose is with a kind of in white sugar, caster sugar, the meticulous caster sugar or two kinds; In described mannitol crystallized mannitol, spray drying mannitol, the melt granulation mannitol more than one.
8. the direct compression of full-powder method of cefuroxime axetil tablets according to claim 7, it is characterized in that: to described CEFUROXIME AXETIL coating tablets, in coating material Opadry coating premix material, positive blue or green coating premix material, hypromellose, ethyl cellulose, polyvinyl alcohol, the titanium dioxide more than one, coating material is 2～3.5% of a cefuroxime axetil tablets label weight.
9. the direct compression of full-powder method of cefuroxime axetil tablets according to claim 8, it is characterized in that: the percentage by weight component that the label of described cefuroxime axetil tablets comprises is: CEFUROXIME AXETIL 45%～60%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～1.5%, starch 5～25%, sucrose 5～20%, mannitol 5～25%.
10. the direct compression of full-powder method of cefuroxime axetil tablets according to claim 9, it is characterized in that: the percentage by weight component that the label of described cefuroxime axetil tablets comprises is: CEFUROXIME AXETIL 50%～55%, ion exchange resin 4%～10%, cross-linking sodium carboxymethyl cellulose 3%～8%, sucrose fatty acid ester 3%～8%, micropowder silica gel 0.5～.1.5%, starch 10～20%, sucrose 10～15%, mannitol 10～20%.
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CN107569466A (en) * 2017-09-17 2018-01-12 石家庄四药有限公司 Cefuroxime axetil pharmaceutical composition prepared by a kind of direct compression method
CN113234092A (en) * 2021-04-13 2021-08-10 伊犁川宁生物技术股份有限公司 Cephalosporin intermediate 7-amino 3-desacetoxy cephalosporanic acid and preparation method thereof

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Publication number Priority date Publication date Assignee Title
CN104785149A (en) * 2015-04-27 2015-07-22 四川制药制剂有限公司 Production technology of preparing orally taken solid preparation
CN107569466A (en) * 2017-09-17 2018-01-12 石家庄四药有限公司 Cefuroxime axetil pharmaceutical composition prepared by a kind of direct compression method
CN113234092A (en) * 2021-04-13 2021-08-10 伊犁川宁生物技术股份有限公司 Cephalosporin intermediate 7-amino 3-desacetoxy cephalosporanic acid and preparation method thereof

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