CN113908133B - Cefixime sustained release tablet and preparation method thereof - Google Patents
Cefixime sustained release tablet and preparation method thereof Download PDFInfo
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- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 title claims abstract description 43
- 229960002129 cefixime Drugs 0.000 title claims abstract description 43
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 15
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 15
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 15
- 239000011247 coating layer Substances 0.000 claims abstract description 12
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 8
- 239000000945 filler Substances 0.000 claims abstract description 8
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims abstract description 6
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000013268 sustained release Methods 0.000 claims abstract description 6
- 239000012730 sustained-release form Substances 0.000 claims abstract description 6
- 239000001069 triethyl citrate Substances 0.000 claims abstract description 6
- 235000013769 triethyl citrate Nutrition 0.000 claims abstract description 6
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011248 coating agent Substances 0.000 claims description 16
- 238000000576 coating method Methods 0.000 claims description 16
- 239000003826 tablet Substances 0.000 claims description 15
- 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 9
- 235000010413 sodium alginate Nutrition 0.000 claims description 9
- 239000000661 sodium alginate Substances 0.000 claims description 9
- 229940005550 sodium alginate Drugs 0.000 claims description 9
- 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 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000008101 lactose Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 8
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 230000004584 weight gain Effects 0.000 claims description 3
- 235000019786 weight gain Nutrition 0.000 claims description 3
- 229910021487 silica fume Inorganic materials 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 229920003151 Eudragit® RL polymer Polymers 0.000 claims 2
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 abstract description 18
- 229940079593 drug Drugs 0.000 abstract description 13
- 229920003155 Eudragit® RL 100 Polymers 0.000 abstract description 4
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940041006 first-generation cephalosporins Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 229940041008 second-generation cephalosporins Drugs 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940126532 prescription medicine Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002485 urinary effect Effects 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
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2813—Inorganic compounds
-
- 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
- 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
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Inorganic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of medicines, and provides a cefixime sustained-release tablet and a preparation method thereof. The sustained release tablet consists of a sustained release tablet core and a sustained release coating layer, wherein the sustained release tablet core comprises cefixime, a filling agent, a disintegrating agent, a glidant, a lubricating agent and a sustained release framework material; the slow release coating layer comprises Eudragit RL 100, ethyl cellulose, triethyl citrate and talcum powder. The cefixime sustained release tablet prepared by the invention has the advantages of slow drug release, simple preparation process, low technical difficulty and good reproducibility of release curve, and is suitable for large-scale production.
Description
Technical Field
The invention belongs to the technical field of medicines, and provides a cefixime sustained-release tablet and a preparation method thereof.
Background
Cefixime is a third-generation cephalosporin antibiotic for oral administration, and is suitable for treating respiratory, urinary and biliary tract infections caused by sensitive bacteria. Cefixime is highly stable against beta-lactamase produced by gram-negative bacilli, has a stronger antibacterial effect on gram-negative bacilli than the first and second generation cephalosporins, and has a lower antibacterial effect on gram-positive cocci than the first and second generation cephalosporins. Cefixime medicine approved by the national food and drug administration has various dosage forms such as tablets, capsules, dispersible tablets, dry suspension, granules and the like, which are prescription medicines, and no sustained release preparation is seen to be marketed.
Cefixime belongs to antibiotics with short half-life period, repeated administration is needed to maintain effective blood concentration, and dosage forms such as tablets, capsules, dispersible tablets, dry suspensions, granules and the like in the prior art are recommended to be administered for 2 times a day, but repeated administration has the defect of large fluctuation of blood concentration, and repeated administration is reduced in medication compliance and cannot be effectively treated for special crowds such as old people and children, so development of a cefixime slow-release preparation is very necessary.
The Chinese patent No. 101084904B discloses a cefixime slow-release double-layer tablet, which consists of a cefixime quick-release layer and a cefixime slow-release layer, wherein the cefixime is dispersed to the quick-release layer and the slow-release layer according to a certain proportion so as to obtain higher initial blood concentration and an ideal blood curve.
Disclosure of Invention
The invention aims to provide a cefixime sustained release tablet and a preparation method thereof, and the cefixime sustained release tablet disclosed by the invention is slow in drug release, so that the blood concentration is stable, the peak-valley phenomenon is avoided, the effective blood concentration can be maintained for a long time, and the optimal treatment effect is exerted. Because the peak-valley phenomenon is reduced, the method is beneficial to reducing the toxic and side effects of the medicine, reducing the occurrence of drug resistance and providing better medication selection for clinical patients.
The specific technical scheme of the invention is as follows:
the cefixime sustained release tablet comprises 80% -95% of sustained release tablet cores and 5% -20% of sustained release coating layers; the sustained-release tablet core comprises cefixime, a filler, a disintegrating agent, a glidant, a lubricant and a sustained-release material; the slow release coating layer comprises Eudragit RL 100, ethyl cellulose, triethyl citrate and talcum powder.
Specifically, the sustained-release tablet core comprises the following components:
the slow release coating layer comprises the following components:
preferably, the sustained-release tablet core comprises the following components:
the slow release coating layer comprises the following components:
further preferably, the sustained-release tablet core comprises the following components
The slow release coating layer comprises the following components:
preferably, the slow release material is one or more of ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carbomer resin, sodium carboxymethyl cellulose and sodium alginate; further preferably, the slow-release framework material is a mixture of ethyl cellulose and sodium alginate; more preferably, the ratio of the ethyl cellulose to the sodium alginate is 1:0.5-5; still more preferably, the ratio of the ethyl cellulose to the sodium alginate is 1:1-3; most preferably, the ratio of the ethyl cellulose to the sodium alginate is 1:2.
Preferably, the filler is a mixture of microcrystalline cellulose and lactose; further preferably, the ratio of the microcrystalline cellulose to lactose is 1:0.5-3; more preferably, the ratio of the microcrystalline cellulose to the lactose is 1:0.8-1.5; most preferably, the ratio of microcrystalline cellulose to lactose is 1:1.
Preferably, the disintegrating agent is one or more of low-substituted hydroxypropyl cellulose, dry starch, sodium carboxymethyl starch and crosslinked PVP; further preferably, the disintegrant is sodium carboxymethyl starch.
Preferably, the glidant is one or two of silica gel and silicon dioxide.
Preferably, the lubricant is one or more of magnesium stearate, micro silica gel, hydrogenated vegetable oil and sodium stearyl fumarate; further preferably, the lubricant is magnesium stearate.
The invention also provides a preparation method of the cefixime sustained-release tablet, namely the preparation method comprises the following steps:
a: taking the prescription dose of cefixime, a filling agent, a disintegrating agent, a slow-release material, a glidant and a lubricant, mixing, tabletting and obtaining a plain tablet for standby;
b: taking the components of the slow-release coating layer with the prescription amount, and preparing coating liquid for standby;
c: and (C) coating the tablet obtained in the step (A) with the coating liquid obtained in the step (B) to obtain the cefixime sustained-release tablet.
Specifically, the preparation method comprises the following steps.
A: mixing cefixime, microcrystalline cellulose, lactose (the proportion is 1:1), carboxymethyl starch sodium, ethyl cellulose, sodium alginate (the proportion is 1:2), glidant and lubricant according to the prescription amount, and tabletting to obtain a tablet for standby;
b: taking a prescription amount of Eudragit RL 100, triethyl citrate, ethyl cellulose and talcum powder, and preparing coating liquid for later use;
c: and (C) coating the tablet obtained in the step (A) with the coating liquid obtained in the step (B) to obtain the cefixime sustained-release tablet.
Preferably, the weight gain of the coating in the step C of the preparation method is 10-15%; further preferred, the coating weight gain is 13%.
Compared with the prior art, the invention has the following technical effects:
1. the invention provides a novel cefixime sustained release preparation, which provides more medication choices for clinical patients, and particularly aims at the people with poor medication compliance such as the old and children, and avoids repeated medication.
2. The cefixime sustained release tablet prepared by the invention has slow release, can effectively avoid the sudden release phenomenon of the drug, can release the drug stably within 24 hours, ensures the safety of clinical medication and has high bioavailability; and the preparation process is simple, the technical difficulty is low, the reproducibility of the release curve is good, and the method is beneficial to industrialized mass production.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Examples 1 to 5:
examples 7 to 11
Examples 12 to 16
Examples 17 to 20
The preparation method comprises the following steps: mixing cefixime, microcrystalline cellulose, lactose, sodium carboxymethyl starch, ethyl cellulose, sodium alginate, micro powder silica gel and magnesium stearate according to the prescription amount, and tabletting to obtain a tablet for standby; taking a prescription amount of Eudragit RL 100, triethyl citrate, ethyl cellulose and talcum powder, and preparing coating liquid for later use; and coating the obtained tablet with the obtained coating liquid (the weight of the coating is increased by 13%) to obtain the cefixime sustained-release tablet.
Comparative examples 1 to 4
Reference is made to the preparation method described above.
Release degree detection
The release degree is measured according to the dissolution rate and the release degree measurement method (second method of the fourth edition of China pharmacopoeia 2015, general rule 0931).
The cefixime slow-release tablets obtained in examples 1-4, examples 7-9, examples 12-16 and comparative examples 1-4 were subjected to a normal operation with 900ml of phosphate buffer solution having pH of 6.8 as a dissolution medium and a rotation speed of 50 rpm, and 10ml was sampled and tested at 1 hour, 3 hours, 9 hours, 12 hours, 15 hours, 20 hours and 24 hours, respectively. The test results are shown in Table 1.
Experimental results show that the cefixime sustained release tablet prepared by the invention can be released stably within 24 hours, so that the release speed of the cefixime can be effectively regulated, and the sudden release phenomenon can be effectively avoided.
TABLE 1 cumulative Release of cefixime in vitro tablet form (%)
| Time (h) | 1 | 3 | 9 | 12 | 15 | 20 | 24 | 14 |
| Example 1 | 23 | 31 | 45 | 58 | 67 | 80 | 89 | 97 |
| Example 2 | 25 | 38 | 49 | 60 | 71 | 83 | 91 | 98 |
| Example 3 | 22 | 33 | 41 | 56 | 65 | 79 | 91 | 96 |
| Example 4 | 18 | 25 | 42 | 53 | 70 | 82 | 91 | 97 |
| Example 7 | 17 | 27 | 39 | 51 | 68 | 79 | 86 | 95 |
| Example 8 | 20 | 29 | 41 | 62 | 71 | 82 | 91 | 98 |
| Example 9 | 33 | 50 | 59 | 67 | 80 | 86 | 90 | 95 |
| Example 12 | 36 | 45 | 53 | 65 | 76 | 85 | 91 | 98 |
| Example 13 | 39 | 48 | 56 | 66 | 78 | 83 | 90 | 95 |
| Example 14 | 21 | 33 | 48 | 61 | 72 | 83 | 91 | 98 |
| Example 15 | 23 | 35 | 49 | 58 | 69 | 78 | 88 | 97 |
| Example 16 | 33 | 52 | 65 | 76 | 83 | 89 | 93 | 98 |
| Comparative example 1 | 53 | 78 | 89 | 93 | 98 | 98 | 98 | 98 |
| Comparative example 2 | 45 | 60 | 75 | 88 | 93 | 97 | 97 | 97 |
| Comparative example 3 | 35 | 49 | 63 | 78 | 90 | 98 | 98 | 98 |
| Comparative example 4 | 48 | 63 | 79 | 86 | 93 | 97 | 97 | 97 |
Besides the in-vitro release degree detection, the inventor also carries out pharmacokinetics investigation on the cefixime sustained-release tablet, and examines the blood concentration of a tested rat within 24 hours after taking the medicine, and the experimental result shows that the blood concentration of the cefixime sustained-release tablet is higher than that of a common tablet after taking the medicine for 6 hours, the blood concentration of the common tablet is in a descending trend, and the cefixime sustained-release tablet always keeps higher and stable blood concentration within 24 hours after taking the medicine, and has better bioavailability.
Claims (3)
1. The cefixime sustained release tablet is characterized by comprising 80% -95% of sustained release tablet cores and 5% -20% of sustained release coating layers;
the sustained-release tablet core comprises the following components:
cefixime 80-120 parts by weight
100-200 parts by weight of filler
5-20 parts by weight of disintegrating agent
0.5 to 3 parts by weight of glidant
0.1 to 1 part by weight of lubricant
50-150 parts by weight of slow-release material;
the slow release material is a mixture of ethyl cellulose and sodium alginate, and the ratio of the ethyl cellulose to the sodium alginate is 1:1-3; the filler is a mixture of microcrystalline cellulose and lactose, and the ratio of the microcrystalline cellulose to the lactose is 1:0.8-1.5; the disintegrating agent is sodium carboxymethyl starch; the glidant is one or two of micro silica gel and silicon dioxide; the lubricant is magnesium stearate;
the slow release coating layer comprises the following components:
eudragit RL 100-20 parts by weight
15-30 parts by weight of triethyl citrate
20-30 parts by weight of ethylcellulose
3-10 parts by weight of talcum powder
The preparation method of the cefixime sustained release tablet comprises the following steps:
a: taking the prescription dose of cefixime, a filling agent, a disintegrating agent, a slow-release material and a glidant, mixing, tabletting and obtaining a plain tablet for standby;
b: taking the components of the slow-release coating layer with the prescription amount, and preparing coating liquid for standby;
c: coating the tablet obtained in the step A with the coating liquid obtained in the step B to obtain the cefixime sustained-release tablet; wherein the coating weight gain in the step C is 10-15%.
2. The cefixime sustained-release tablet according to claim 1, wherein the sustained-release tablet core comprises the following components:
cefixime 80-120 parts by weight
120-150 parts by weight of filler
8-15 parts by weight of disintegrating agent
1-2 parts by weight of glidant
0.5 to 0.8 part by weight of lubricant
70-100 parts of slow release material.
3. The cefixime sustained-release tablet according to claim 1, wherein the sustained-release coating layer comprises the following components:
eudragit RL 100-16 parts by weight
18-25 parts by weight of triethyl citrate
23-27 parts by weight of ethylcellulose
5-8 parts of talcum powder.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002056867A2 (en) * | 2001-01-18 | 2002-07-25 | Natco Pharma Limited | Extended release pharmaceutical compositions containing beta-lactam antibiotics |
| WO2004019901A2 (en) * | 2002-08-30 | 2004-03-11 | Orchid Chemicals & Pharmaceuticals Ltd. | Sustained release pharmaceutical composition |
| CN101084904A (en) * | 2007-06-15 | 2007-12-12 | 重庆医药工业研究院有限责任公司 | Cefixime sustained-release double-layer tablet |
| CN101496791A (en) * | 2008-01-29 | 2009-08-05 | 济南百诺医药科技开发有限公司 | Cefixime sustained-release tablets and preparation method thereof |
| CN103655506A (en) * | 2012-09-11 | 2014-03-26 | 南京亿华药业有限公司 | Cefaclor sustained release tablet and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090060995A1 (en) * | 2005-01-13 | 2009-03-05 | Kamalinder Kaur Singh | Dispersible sustained release pharmaceutical compositions |
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2021
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002056867A2 (en) * | 2001-01-18 | 2002-07-25 | Natco Pharma Limited | Extended release pharmaceutical compositions containing beta-lactam antibiotics |
| WO2004019901A2 (en) * | 2002-08-30 | 2004-03-11 | Orchid Chemicals & Pharmaceuticals Ltd. | Sustained release pharmaceutical composition |
| CN101084904A (en) * | 2007-06-15 | 2007-12-12 | 重庆医药工业研究院有限责任公司 | Cefixime sustained-release double-layer tablet |
| CN101496791A (en) * | 2008-01-29 | 2009-08-05 | 济南百诺医药科技开发有限公司 | Cefixime sustained-release tablets and preparation method thereof |
| CN103655506A (en) * | 2012-09-11 | 2014-03-26 | 南京亿华药业有限公司 | Cefaclor sustained release tablet and preparation method thereof |
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| CN113908133A (en) | 2022-01-11 |
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