CN117243913A - Cefaclor sustained-release composition and preparation method thereof - Google Patents
Cefaclor sustained-release composition and preparation method thereof Download PDFInfo
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- CN117243913A CN117243913A CN202311383617.1A CN202311383617A CN117243913A CN 117243913 A CN117243913 A CN 117243913A CN 202311383617 A CN202311383617 A CN 202311383617A CN 117243913 A CN117243913 A CN 117243913A
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- cefaclor
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- inner layer
- release composition
- outer layer
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- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 title claims abstract description 70
- 229960005361 cefaclor Drugs 0.000 title claims abstract description 70
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 238000013268 sustained release Methods 0.000 title claims abstract description 29
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 29
- 239000000463 material Substances 0.000 claims abstract description 60
- 239000002994 raw material Substances 0.000 claims abstract description 29
- 239000007939 sustained release tablet Substances 0.000 claims abstract description 21
- 239000011248 coating agent Substances 0.000 claims abstract description 19
- 238000000576 coating method Methods 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 10
- 238000005260 corrosion Methods 0.000 claims abstract 2
- 230000007797 corrosion Effects 0.000 claims abstract 2
- 238000002156 mixing Methods 0.000 claims description 47
- 238000007873 sieving Methods 0.000 claims description 46
- 239000003826 tablet Substances 0.000 claims description 33
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 32
- 239000002245 particle Substances 0.000 claims description 23
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 230000001050 lubricating effect Effects 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
- 238000007908 dry granulation Methods 0.000 claims description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 229940069328 povidone Drugs 0.000 claims description 8
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 7
- 229930006000 Sucrose Natural products 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 229940049654 glyceryl behenate Drugs 0.000 claims description 7
- 238000005469 granulation Methods 0.000 claims description 7
- 230000003179 granulation Effects 0.000 claims description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 7
- 239000005720 sucrose Substances 0.000 claims description 7
- 235000021355 Stearic acid Nutrition 0.000 claims description 6
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 6
- 239000008117 stearic acid Substances 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 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 5
- 239000008101 lactose Substances 0.000 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- 239000005434 MCC/mannitol excipient Substances 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 4
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 4
- 238000007781 pre-processing Methods 0.000 claims description 4
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 4
- 239000000853 adhesive Substances 0.000 claims description 3
- 230000001070 adhesive effect Effects 0.000 claims description 3
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 3
- 230000003628 erosive effect Effects 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 229940075529 glyceryl stearate Drugs 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 229940057948 magnesium stearate Drugs 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 229960001866 silicon dioxide Drugs 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229960004274 stearic acid Drugs 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 239000003361 porogen Substances 0.000 claims 1
- 238000004513 sizing Methods 0.000 claims 1
- 239000000843 powder Substances 0.000 abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 239000003960 organic solvent Substances 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 8
- 239000004925 Acrylic resin Substances 0.000 abstract description 7
- 229920000178 Acrylic resin Polymers 0.000 abstract description 7
- 238000004880 explosion Methods 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 230000007246 mechanism Effects 0.000 abstract description 3
- 239000002861 polymer material Substances 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000010410 layer Substances 0.000 description 56
- 230000001276 controlling effect Effects 0.000 description 11
- 229960003943 hypromellose Drugs 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000012943 hotmelt Substances 0.000 description 10
- 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 description 8
- 229930195725 Mannitol Natural products 0.000 description 8
- 239000000594 mannitol Substances 0.000 description 8
- 235000010355 mannitol Nutrition 0.000 description 8
- 238000005550 wet granulation Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000008119 colloidal silica Substances 0.000 description 5
- 239000007888 film coating Substances 0.000 description 5
- 238000009501 film coating Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- WKJGTOYAEQDNIA-IOOZKYRYSA-N (6r,7r)-7-[[(2r)-2-amino-2-phenylacetyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrate Chemical compound O.C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 WKJGTOYAEQDNIA-IOOZKYRYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000004080 punching Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000007907 direct compression Methods 0.000 description 3
- 238000007909 melt granulation Methods 0.000 description 3
- 238000009475 tablet pressing Methods 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 229950005770 hyprolose Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940124588 oral cephalosporin Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the field of pharmaceutical preparations, in particular to a cefaclor sustained-release composition and a preparation method thereof, wherein the cefaclor sustained-release composition comprises an inner layer and an outer layer, the inner layer is a hydrophilic gel layer, the outer layer is a waxy corrosion layer, and the preparation method of the cefaclor sustained-release composition comprises the following steps: preparing an inner layer intermediate; preparing an outer layer intermediate; tabletting; and (5) coating. According to the invention, a double-layer release mechanism is adopted to prepare the cefaclor sustained-release tablet, and polymer materials such as an organic solvent, water and acrylic resin are not required to be added in the preparation process, so that the problems of material stickiness caused by adding water in the process and low content caused by raw material adhesion equipment with poor process compliance can be effectively avoided, explosion prevention and environmental pollution caused by adding the organic solvent can be avoided, in addition, the problem that the material fluidity is poor and tabletting is impossible when independent powder is directly pressed is solved, the dissolution speed is regulated and controlled through the cooperation of the inner layer and the outer layer, and the self-made product has good release degree and better stability.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a cefaclor sustained-release composition and a preparation method thereof.
Background
Cefaclor was first developed and marketed by Gift America, belongs to the second generation of oral cephalosporins, has strong killing effect on various gram-positive bacteria and gram-negative bacteria, and is mainly used for treating respiratory tract infection, urinary tract infection, gonorrhea bacteria infection, otitis media and other diseases. The existing cefaclor preparation forms comprise a plurality of preparation forms such as tablets, capsules, granules, sustained-release pellets, sustained-release tablets, dispersible tablets and the like, wherein the cefaclor sustained-release tablet is the only one cefaclor sustained-release preparation worldwide and has better clinical advantages.
The cefaclor ordinary preparation is generally taken three times per day, the taking times are high, inconvenience is brought to patients, and the cefaclor sustained-release tablet just overcomes the defect, so that the cefaclor sustained-release tablet not only maintains the original antibacterial property, but also has the advantages of long half-life, reduced taking times, improved compliance and the like, thereby improving the compliance of patients.
At present, the cefaclor sustained-release tablets on the market are mainly prepared by adopting an organic solvent (such as ethanol, isopropanol and the like) for wet granulation, and most of the cefaclor sustained-release tablets need to be added with acrylic resin or other polymers, the powder direct compression of the materials is difficult to realize due to the powder properties, the existing process and prescription have the problems of explosion prevention and pollution of the organic solvent, poor material fluidity and incapability of tabletting during the powder direct compression, raw materials and auxiliary materials are sticky when meeting water due to the adoption of a water granulation process, the process compliance is poor, the stability is poor and the like
Therefore, there is a need to provide a new cefaclor sustained release composition and a preparation method thereof.
Disclosure of Invention
In view of the above, the present invention aims to provide a cefaclor sustained-release composition and a preparation method thereof, so as to solve the problems in the prior art.
Based on the above purpose, the invention provides a cefaclor sustained-release composition and a preparation method thereof.
A cefaclor sustained release composition comprising an inner layer and an outer layer;
the raw material dosage ratio of the inner layer to the outer layer is 500-900:100-50;
the material dosage ratio of the inner layer to the outer layer is 625-1315:145-760;
the inner layer is a hydrophilic gel layer, and the outer layer is a wax erosion layer.
Furthermore, the invention also provides a preparation method of the cefaclor sustained-release composition, which comprises the following specific preparation steps:
s1, respectively sieving and preprocessing an inner layer raw material and an inner layer auxiliary material, then adding the inner layer raw material and the inner layer auxiliary material into a mixer, uniformly mixing, carrying out dry granulation by a dry granulator, sieving and granulating, adding an inner layer lubricating glidant, and mixing to obtain an inner layer intermediate;
s2, respectively sieving and preprocessing the outer layer raw materials and the outer layer auxiliary materials, uniformly mixing, carrying out hot melt granulation in a hot melt wet granulator, sieving and granulating, adding an outer layer lubricating glidant, and mixing to obtain an outer layer intermediate;
s3, adding the inner layer intermediate and the outer layer intermediate into a tablet press for tabletting;
s4, coating the tablet prepared by the tablet pressing machine in the step S3 to obtain the cefaclor sustained release tablet.
Further, in step S1, the weight ratio of the inner layer raw material, the inner layer auxiliary material and the inner layer lubricating glidant is 500-900:120-400:5-15.
Further, the inner layer raw material is cefaclor raw material, the particle size D50 of the cefaclor raw material is 5-30 mu m, and the D90 of the cefaclor raw material is 20-170 mu m.
Further, the inner layer auxiliary material is obtained by mixing an inner layer filler, an inner layer pore-forming agent, an inner layer adhesive and a hydrophilic framework material according to the weight ratio of 15-75:15-75:10-100:80-150.
Further, the inner layer lubricating glidant is any one of magnesium stearate, stearic acid, sodium stearyl fumarate, silicon dioxide and colloidal silicon dioxide.
Further, the inner filler is any one of microcrystalline cellulose and mannitol.
Further, the inner layer pore-forming agent is any one of lactose and povidone.
Further, the inner layer binder is any one of hydroxypropyl cellulose and starch.
Further, the hydrophilic framework material is any one of hypromellose, sodium alginate and chitosan.
Further, in the step S1, the pressure of a granulating roller is 6-18MPa when the dry granulating machine is used for granulating, and a granulating screen is a 10-30-mesh screen.
Further, in step S2, the weight ratio of the outer layer raw material, the outer layer auxiliary material and the outer layer lubricating glidant is 100-500:40-250:5-10, wherein the outer layer raw material is cefaclor raw material, the particle size D50 of the cefaclor raw material is 5-20 mu m, and the D90 of the cefaclor raw material is 10-100 mu m.
Further, the outer auxiliary material is obtained by mixing an outer filler, an outer pore-forming agent, an outer adhesive and a wax erosion framework material according to the weight ratio of 5-30:5-30:0-40:30-150.
Further, the outer layer lubricating glidant is any one of magnesium stearate, stearic acid and sodium stearyl fumarate.
Further, the outer filler is any one of microcrystalline cellulose and mannitol.
Further, the outer layer pore-forming agent is any one of lactose and sucrose.
Further, the outer layer binder is any one of povidone, hydroxypropyl cellulose and starch.
Further, the waxy framework material is any one of glyceryl behenate, stearic acid, hydrogenated vegetable oil and glyceryl stearate.
Further, in the step S2, the temperature of a granulating pot body of the hot melt wet granulator is 60-90 ℃, the stirring rotation speed is 1-5r/S, the cutter speed is 10-30r/S, the granulating time is 5-20min, and the whole granulating screen is 14-30 mesh screen.
Further, the coating layer is a gastric-soluble film coating premix.
The invention has the beneficial effects that:
the invention provides a cefaclor sustained-release composition and a preparation method thereof, wherein a double-layer release mechanism is adopted to prepare the cefaclor sustained-release tablet, organic solvents and water are not needed to be added in the preparation process, polymer materials such as acrylic resin and the like are not needed to be added, on one hand, the problems of material stickiness caused by adding water in the process and low content caused by raw material adhesion equipment with poor process compliance can be effectively avoided, explosion prevention and environmental pollution caused by adding organic solvents can be avoided, in addition, the problem that the material fluidity is poor and tabletting cannot be carried out when independent powder is directly pressed is solved, the dissolution speed is regulated and controlled through the cooperation of the inner layer and the outer layer, and the self-made product has good release degree and better stability.
Detailed Description
The present invention will be further described in detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent.
Example 1
The preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, firstly, passing 1500g of cefaclor with the particle size D50 of 5-30 mu m and the particle size D90 of 20-170 mu m through a 60-mesh screen, passing 175g of hypromellose through a 40-mesh screen, passing 150g of mannitol through a 60-mesh screen, passing 2g of colloidal silica through a 100-mesh screen, then putting 75g of hypromellose into a mixer, mixing at the speed of 10rpm for 10min, then putting the materials into a dry granulator for dry granulation, setting the roller pressure of 6MPa, setting the roller clearance of 0.5mm, granulating the mesh number of 10-30 meshes, selecting the 10-60-mesh screen for sieving, repeatedly granulating fine powder, ensuring that the yield of 10-60-mesh particles is 40-80%, then putting the materials into the mixer together with 20g of magnesium stearate passing through a 100-mesh screen for mixing, mixing at the speed of 10rpm for 3min, and obtaining an inner layer intermediate after mixing;
s2, firstly, 375g of cefaclor with the particle size D50 of 5-20 mu m and the particle size D90 of 10-100 mu m is sieved by a 80-mesh sieve, 100g of glyceryl behenate is sieved by a 40-mesh sieve, 125g of sucrose is crushed and then is sieved by a 60-mesh sieve, 50g of povidone is sieved by a 60-mesh sieve, then the mixture is put into a mixer, the speed of 10rpm is mixed for 5min, the temperature of a liquid tank of a hot melt wet granulator is set to 90 ℃, the mixed material is added when the temperature of the material in the pot is about 75 ℃, the rotating speed of a stirring frame is 1r/s, the cutter speed is 10r/s, the granulating time is 5min, the granulated material is slightly cooled, then is sieved by a 14-30-mesh sieve, and then the mixture and 7.5g of magnesium stearate which is sieved by a 100-mesh sieve are put into the mixer for mixing, the mixing speed is 10rpm, and the mixing speed is 3min, and an outer layer intermediate is obtained;
s3, respectively adding 1922g of the inner intermediate and 747.5g of the outer intermediate into a tablet press to perform tablet pressing, wherein a punching film is a 16X 8mm elliptic sheet, setting the main pressure of the tablet press to 15kN, controlling the weight of the sheet according to +/-5% of the theoretical sheet weight, and controlling the hardness to be 120-180N;
s4, preparing 90g of film coating premix into suspension with 10% of solid content by adopting an aqueous solution, stirring for 1h, sieving with a 80-mesh sieve, and coating the tablet prepared in the step S3, wherein the temperature of the tablet bed is controlled between 38 and 45 ℃, and the weight of the coating is increased by about 2%, so as to obtain the cefaclor sustained-release tablet.
Example 2
The preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, firstly, passing 1375g of cefaclor with the particle size D50 of 5-30 mu m and the particle size D90 of 20-170 mu m through a 60-mesh screen, passing 200g of hypromellose through a 40-mesh screen, passing 175g of mannitol through a 60-mesh screen, passing 2g of colloidal silica through a 100-mesh screen, putting 75g of hyprolose into a mixer, mixing at the speed of 10rpm for 10min, putting the materials into a dry granulator for dry granulation, setting the roller pressure of 12MPa, setting the roller clearance of 1.5mm, granulating the mesh number of 10-30 meshes, selecting the 10-60-mesh screen for sieving, repeatedly granulating fine powder, ensuring that the yield of 10-60-mesh particles is 40-80%, mixing with 20g of magnesium stearate which passes through a 100-mesh screen, putting the mixture into the mixer for mixing at the speed of 10rpm, mixing for 5min, and obtaining an inner layer intermediate after mixing;
s2, firstly, sieving 500g of cefaclor with the particle size of 5-20 mu m and the particle size of D90 of 10-100 mu m by a 80-mesh sieve, sieving 80g of glyceryl behenate by a 60-mesh sieve, crushing 145g of sucrose, sieving by a 60-mesh sieve, sieving 50g of povidone by a 60-mesh sieve, then putting into a mixer, mixing at the speed of 10rpm for 5min, setting the temperature of a liquid tank of a hot melt wet granulator at 85 ℃, adding the mixed materials at the temperature of about 80 ℃ in a pot body, stirring at the speed of a stirring frame of 3r/s, the cutter speed of 20r/s, the granulating time of 7.5min, slightly cooling the granulated materials, sieving by a 14-30-mesh sieve, then putting into the mixer with 7.5g of magnesium stearate with the sieve of 100 meshes, mixing at the speed of 10rpm, and mixing for 5min to obtain an outer layer intermediate;
s3, respectively adding 1847g of the inner layer intermediate and 872.5g of the outer layer intermediate into a tablet press to perform tablet pressing, wherein a punching film is a 16X 8mm elliptic sheet, the main pressure of the tablet press is set to be 20kN, the weight of the tablet is controlled to be 130-190N according to +/-5% of the theoretical tablet weight;
s4, preparing 90g of film coating premix into a suspension with 15% of solid content by adopting an aqueous solution, stirring for 1h, sieving with a 60-mesh sieve, and coating the tablet prepared in the step S3, wherein the temperature of the tablet bed is controlled between 45 and 50 ℃, and the weight of the coating is increased by about 3.5%, so that the cefaclor sustained-release tablet is obtained.
Example 3
The preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, firstly, 1650g of cefaclor with the particle size D50 of 5-30 mu m and D90 of 20-170 mu m is sieved by a 60-mesh sieve, 150g of hypromellose is sieved by a 40-mesh sieve, 150g of mannitol is sieved by a 60-mesh sieve, 2g of colloidal silica is sieved by a 100-mesh sieve, 100g of hypromellose is put into a mixer, the mixing speed is 10rpm, the materials are put into a dry granulator for dry granulation, the roller pressure is set to be 18MPa, the roller clearance is 2.0mm, the mesh number of the granulating sieve is 10-30 meshes, the sieve with the mesh size of 10-60 meshes is selected for sieving, the fine powder is repeatedly granulated, the granulation is stopped at 40-80% of the particle yield of 10-60 meshes, then the mixture and 20g of magnesium stearate which is sieved by a 100-mesh sieve are put into the mixer for mixing, the mixing speed is 10rpm, the mixture is mixed for 7min, and the inner layer intermediate is obtained;
s2, firstly, sieving 225g of cefaclor with the particle size of 5-20 mu m and the particle size of D90 of 10-100 mu m by a 80-mesh sieve, sieving 150g of glyceryl behenate by a 40-mesh sieve, sieving 100g of sucrose by a 60-mesh sieve after being crushed, sieving 75g of povidone by a 60-mesh sieve, then putting into a mixer, mixing at the speed of 10rpm for 5min, setting the temperature of a liquid tank of a hot melt wet granulator at 88 ℃, adding the mixed materials when the temperature of the materials in a pot body is about 70 ℃, the rotating speed of a stirring frame at the speed of 5r/s, the cutter speed of 30r/s, the granulating time of 10min, slightly cooling the granulated materials, sieving by a 14-30-mesh sieve, then putting into the mixer with 7.5g of magnesium stearate sieving by a 100-mesh sieve, mixing at the speed of 10rpm, and mixing for 7min to obtain an outer layer intermediate;
s3, respectively adding 2072g of the inner intermediate and 647.5g of the outer intermediate into a tablet press for tabletting, wherein a punching film is a 16X 8mm elliptic piece, the main pressure of the tablet press is set to be 30kN, the weight of the tablet is controlled to be 160-220N according to +/-5% of the theoretical tablet weight;
s4, preparing 90g of film coating premix into a suspension with 20% of solid content by adopting an aqueous solution, stirring for 1h, sieving with a 60-mesh sieve, and coating the tablet prepared in the step S3, wherein the temperature of the tablet bed is controlled between 50 and 55 ℃, and the weight of the coating is increased by about 4%, so as to obtain the cefaclor sustained-release tablet.
Example 4
The preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, firstly, 940g of cefaclor with the particle size D50 of 5-30 mu m and D90 of 20-170 mu m is sieved by a 60-mesh sieve, 100g of hypromellose is sieved by a 40-mesh sieve, 150g of mannitol is sieved by a 60-mesh sieve, 2g of colloidal silica is sieved by a 100-mesh sieve, 100g of hypromellose is put into a mixer, the speed of 10rpm is mixed for 10min, then the materials are put into a dry granulator for dry granulation, the roller pressure is set to be 18MPa, the roller clearance is 2.0mm, the number of granulating screens is 10-30 meshes, the 10-60-mesh sieve is selected for sieving, the fine powder is repeatedly granulated, the granulation is stopped at 40-80% of the particle yield of 10-60 meshes, then the materials and 20g of magnesium stearate which passes through the 100-mesh sieve are put into the mixer for mixing, the mixing speed is 10rpm, the materials are mixed for 7min, and an inner layer intermediate is obtained after the mixing;
s2, firstly sieving 935g of cefaclor with the particle size of 5-20 mu m and the particle size of D90 of 10-100 mu m with a 80-mesh sieve, sieving 175g of glyceryl behenate with a 80-mesh sieve, sieving 115g of sucrose with a 60-mesh sieve, sieving 50g of povidone with a 60-mesh sieve, then putting into a mixer, mixing at the speed of 10rpm for 5min, setting the temperature of a liquid tank of a hot melt wet granulator at 90 ℃, adding the mixed materials when the temperature of the materials in a pot is about 70 ℃, the rotating speed of a stirring frame at 5r/s, the cutter speed at 30r/s, the granulating time at 10min, slightly cooling the granulated materials, sieving with a 14-30-mesh sieve, then putting into the mixer with 7.5g of magnesium stearate with a 100-mesh sieve, mixing at the speed of 10rpm, and mixing for 7min to obtain an outer layer intermediate;
s3, respectively adding 1312g of the inner intermediate and 1282.5g of the outer intermediate into a tablet press for tabletting, wherein a punching film is a 16X 8mm elliptic piece, setting the main pressure of the tablet press to 18kN, and controlling the weight of the piece to be 140-200N according to +/-5% of the theoretical weight of the piece;
s4, preparing 90g of film coating premix into a suspension with 15% of solid content by adopting an aqueous solution, stirring for 1h, sieving with a 80-mesh sieve, and coating the tablet prepared in the step S3, wherein the temperature of the tablet bed is controlled between 38 and 42 ℃, and the weight of the coating is increased by about 2.6%, so as to obtain the cefaclor sustained-release tablet.
Comparative example 1 (wet granulation of aqueous solution)
The preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, dissolving 30g of hydroxypropyl cellulose in 300g of water, then sieving 1100g of cefaclor monohydrate and 70g of mannitol with a 60-mesh sieve, sieving 40g of hydroxypropyl methylcellulose E5 and 200g of hydroxypropyl methylcellulose E50 respectively with a 40-mesh sieve, adding the materials and 10g of acrylic resin into a granulator, mixing for 5min, adding 30g of hydroxypropyl cellulose HPC aqueous solution for wet granulation, preparing a soft material for about 3min, and sieving with a 18-30-mesh sieve for wet granulation;
s2, drying in a fluidized bed, discharging from a pot for drying and granulating (18-30 meshes), and mixing the product with 20g of magnesium stearate (passing through a 100-mesh screen) for 3min to obtain an intermediate;
s3, tabletting (special-shaped tablets are 16 multiplied by 8mm elliptic tablets) according to the theoretical content, controlling the hardness to be 120-180N, coating, and controlling the weight gain of the coating to be about 2.5%, thus obtaining the cefaclor sustained-release tablets.
Comparative example 2 (ethanol wet granulation)
S1, dissolving 15g of acrylic resin in 300g of ethanol, then sieving 1100g of cefaclor monohydrate and 80g of mannitol with a 60-mesh sieve, sieving 30g of hydroxypropyl cellulose, 35g of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K4M with a 40-mesh sieve respectively, adding the materials into a granulator, mixing for 5min, adding an acrylic resin ethanol solution for wet granulation, preparing a soft material for about 3-10min, and sieving with a 18-30-mesh sieve for wet granulation;
s2, drying in a fluidized bed, discharging from a pot for drying and granulating (18-30 meshes), and mixing the product with 20g of magnesium stearate (passing through a 100-mesh screen) for 3min to obtain an intermediate;
s3, tabletting (special-shaped tablets are 16 multiplied by 8mm elliptic tablets) according to the theoretical content, controlling the hardness to be 120-160N, coating, and controlling the weight gain of the coating to be about 3.5%, thus obtaining the cefaclor sustained-release tablets.
Comparative example 3 (Dry granulation alone)
S1, firstly, 1100g of cefaclor monohydrate, 70g of mannitol and 20g of lactose are screened by a 60-mesh screen, 40g of povidone K30, 40g of hypromellose E5 and hypromellose K100LV are respectively screened by a 40-mesh screen, 5g of colloidal silica is screened by a 100-mesh screen, the materials are mixed in a mixer for 5min, then the materials are put into a dry granulator for dry granulation, the roller pressure is set to be 6MPa, the roller gap is 0.5mm, the number of the granulating screens is 10-30 meshes, the screen with 10-60 meshes is selected for sieving, fine powder is repeatedly granulated, the granulation is stopped at 40-80% of the particle yield with 10-60 meshes, then the materials and 20g of magnesium stearate (screened by 100 meshes) are put into the mixer for mixing, the mixing speed is 10rpm, and the mixture is mixed for 3min, and then an intermediate is obtained;
s2, tabletting (special-shaped tablets are 16 multiplied by 8mm elliptic tablets) according to the theoretical content, controlling the hardness to be 120N-160N, coating, and controlling the coating weight to be increased by about 3 percent, thus obtaining the cefaclor sustained-release tablets.
Comparative example 4 (separate hot melt granulation)
S1, firstly, sieving 1100g of cefaclor monohydrate with a 80-mesh sieve, sieving 70g of mannitol and 20g of crushed sucrose with a 60-mesh sieve, sieving 40g of povidone K30 and 15g of hypromellose E5 with a 40-mesh sieve, sieving 5g of colloidal silicon dioxide with a 100-mesh sieve, sieving 240g of glyceryl behenate with a 40-mesh sieve, putting the materials into a mixer, mixing at 10rpm for 5min, setting the temperature of a liquid tank of a hot melt wet granulator at 85 ℃, adding the mixed materials at about 75 ℃ when the temperature of the materials in the pot is about 1r/s, the speed of a cutter at 10r/s, granulating for 5min, slightly cooling the granulated materials, sieving with a 14-30-mesh sieve, putting the materials and 20g of magnesium stearate (sieving with 100 meshes) into the mixer together, mixing at 10rpm, and mixing for 3min to obtain an intermediate;
s2, tabletting (special-shaped tablets are 16 multiplied by 8mm elliptic tablets) according to the theoretical content, controlling the hardness to be 140-180N, coating, and controlling the weight gain of the coating to be about 3%, thus obtaining the cefaclor sustained-release tablets.
Performance testing
Release test and acceleration test:
the release degree measurement, the related substances and content test and the acceleration test were carried out by taking examples 1 to 4 and comparative examples 1 to 4, and the results are shown in tables 1, 2 and 3 below:
TABLE 1 Release degree measurement results
Table 2 related substances and results of measurement of content
TABLE 3 accelerated test related substances and content measurement results
Data analysis:
as can be seen from table 1, the release of the product using wet granulation, dry granulation alone and hot melt granulation was slow and not complete, whereas the release was significantly faster with ethanol granulation.
As can be seen from Table 2, the cefaclor sustained-release tablets prepared by the method of the invention have the advantages that the related substances and the content meet the requirements, the related substances are lower than those of the comparative examples, the related substances are increased when the organic solvent is added, the water granulation causes the adhesion of the materials to cause the adhesion of the raw materials, and finally the content is obviously lower.
From Table 3, the cefaclor sustained-release tablet prepared by the invention has the advantages that the relevant substances are lower than other prescription proportions in 0 day, and after the stability is accelerated and examined, the stability of the product prepared by the preferable prescription and preparation method is good.
In conclusion, the cefaclor sustained-release tablet is prepared by adopting a double-layer release mechanism, does not need to add an organic solvent and water or polymer materials such as acrylic resin, can solve the problems that materials are easy to adhere when water is added in the process, and the problems of explosion prevention, environmental pollution and the like when the organic solvent is added, besides, the problem that independent powder is poor in flowability of direct-compression materials and cannot be tabletted is solved, the dissolution speed is regulated and controlled cooperatively through the inner layer and the outer layer, and the self-made product is good in release degree and stability.
Those of ordinary skill in the art will appreciate that: the discussion of any of the embodiments above is merely exemplary and is not intended to suggest that the scope of the invention (including the claims) is limited to these examples; the technical features of the above embodiments or in the different embodiments may also be combined within the idea of the invention, the steps may be implemented in any order and there are many other variations of the different aspects of the invention as described above, which are not provided in detail for the sake of brevity.
The present invention is intended to embrace all such alternatives, modifications and variances which fall within the broad scope of the appended claims. Therefore, any omission, modification, equivalent replacement, improvement, etc. of the present invention should be included in the scope of the present invention.
Claims (10)
1. A cefaclor sustained release composition, which is characterized by comprising an inner layer and an outer layer;
the raw material dosage ratio of the inner layer to the outer layer is 500-900:100-500; the material consumption ratio of the inner layer and the outer layer is as follows: 625-1315:145-760;
the inner layer is a hydrophilic gel layer, and the outer layer is a wax erosion layer;
the preparation method of the cefaclor sustained-release composition comprises the following specific preparation steps:
s1, respectively sieving and preprocessing an inner layer raw material and an inner layer auxiliary material, uniformly mixing, granulating by a dry method, sieving and granulating, adding an inner layer lubricating and/or flow aid, and mixing to obtain an inner layer intermediate;
s2, respectively sieving and preprocessing the outer layer raw materials and the outer layer auxiliary materials, uniformly mixing, carrying out hot melting granulation, sieving and granulating, adding an outer layer lubricating and/or flow aid, and mixing to obtain an outer layer intermediate;
s3, adding the inner layer intermediate and the outer layer intermediate into a tablet press according to a prescription proportion for tabletting;
s4, coating the tablet prepared in the step S3 to obtain the cefaclor sustained release tablet.
2. The cefaclor sustained-release composition according to claim 1, wherein in step S1, the weight ratio of the inner layer raw material, the inner layer auxiliary material and the inner layer lubricating glidant is 500-900:120-400:5-15.
3. The cefaclor sustained-release composition according to claim 2, wherein the inner layer raw material is cefaclor raw material having a particle diameter D50 of 5-30 μm and D90 of 20-170 μm.
4. The cefaclor sustained-release composition according to claim 2, wherein the inner auxiliary material is obtained by mixing an inner filler, an inner pore-forming agent, an inner adhesive and a hydrophilic framework material according to a weight ratio of 15-75:15-75:10-100:80-150, and the inner lubricating glidant is any one or more of magnesium stearate, stearic acid, sodium stearyl fumarate, silicon dioxide and colloidal silicon dioxide.
5. The cefaclor sustained-release composition according to claim 4, wherein the inner filler is any one of microcrystalline cellulose and mannitol, the inner porogen is any one of lactose and povidone, the inner binder is any one of hydroxypropyl cellulose and starch, and the hydrophilic skeleton material is any one of hydroxypropyl methylcellulose, sodium alginate and chitosan.
6. The cefaclor sustained-release composition according to claim 1, wherein the roller pressure in the dry granulation in step S1 is 6 to 18MPa and the sizing screen is a 10 to 30 mesh screen.
7. The cefaclor sustained-release composition according to claim 1, wherein in step S2, the weight ratio of the outer layer raw material, the outer layer auxiliary material and the outer layer lubricating glidant is 100-500:40-250:5-10, wherein the outer layer raw material is cefaclor raw material, the particle size D50 of the cefaclor raw material is 5-20 mu m, and the D90 of the cefaclor raw material is 10-100 mu m.
8. The cefaclor sustained-release composition according to claim 1, wherein in step S2, the outer auxiliary material is an outer filler, an outer pore-forming agent, an outer binder and a waxy corrosion framework material, which are mixed according to a weight ratio of 5-30:5-30:0-40:30-150, and the outer lubricating glidant is any one or more of magnesium stearate, stearic acid and sodium stearyl fumarate.
9. The cefaclor sustained-release composition according to claim 8, wherein the outer filler is any one of microcrystalline cellulose and mannitol, the outer pore-forming agent is any one of lactose and sucrose, the outer binder is any one of povidone, hydroxypropyl cellulose and starch, and the waxy skeleton material is any one of glyceryl behenate, stearic acid, hydrogenated vegetable oil and glyceryl stearate.
10. The cefaclor sustained-release composition according to claim 1, wherein in step S2, the temperature of the granulating pot body is 60-90 ℃, the stirring speed is 1-5r/S, the cutter speed is 10-30r/S, the granulating time is 5-20min, and the granulating screen is 14-30 mesh screen.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040005361A1 (en) * | 2002-07-06 | 2004-01-08 | Sanjeev Khandelwal | Pharmaceutical preparations |
| WO2004019901A2 (en) * | 2002-08-30 | 2004-03-11 | Orchid Chemicals & Pharmaceuticals Ltd. | Sustained release pharmaceutical composition |
| CN103623412A (en) * | 2013-12-13 | 2014-03-12 | 上海新亚药业闵行有限公司 | Stable cefaclor tablet composition and preparation method thereof |
| CN104825415A (en) * | 2015-04-30 | 2015-08-12 | 南通市康桥油脂有限公司 | Cefaclor sustained release preparation and preparation method thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040005361A1 (en) * | 2002-07-06 | 2004-01-08 | Sanjeev Khandelwal | Pharmaceutical preparations |
| WO2004019901A2 (en) * | 2002-08-30 | 2004-03-11 | Orchid Chemicals & Pharmaceuticals Ltd. | Sustained release pharmaceutical composition |
| CN103623412A (en) * | 2013-12-13 | 2014-03-12 | 上海新亚药业闵行有限公司 | Stable cefaclor tablet composition and preparation method thereof |
| CN104825415A (en) * | 2015-04-30 | 2015-08-12 | 南通市康桥油脂有限公司 | Cefaclor sustained release preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| MICHAELA GAJDOŠOVÁ等: "Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging", 《INT J PHARM .》, vol. 500, no. 1, 16 March 2016 (2016-03-16), pages 136 - 143, XP029416959, DOI: 10.1016/j.ijpharm.2016.01.023 * |
| 吴康等: "以羟丙基甲基纤维素为骨架的缓释片阻释剂研究", 《中国药业》, vol. 14, no. 1, 25 January 2005 (2005-01-25), pages 2 - 3 * |
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