CN1569021A - Enteric-coated azithromycin preparation and its preparing process - Google Patents
Enteric-coated azithromycin preparation and its preparing process Download PDFInfo
- Publication number
- CN1569021A CN1569021A CN 200410036629 CN200410036629A CN1569021A CN 1569021 A CN1569021 A CN 1569021A CN 200410036629 CN200410036629 CN 200410036629 CN 200410036629 A CN200410036629 A CN 200410036629A CN 1569021 A CN1569021 A CN 1569021A
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- Prior art keywords
- acid
- azithromycin
- preparation
- enteric
- agent
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Links
- 229960004099 azithromycin Drugs 0.000 title claims abstract description 76
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 title claims abstract description 76
- 238000002360 preparation method Methods 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 26
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 25
- 239000000314 lubricant Substances 0.000 claims abstract description 13
- 239000011230 binding agent Substances 0.000 claims abstract description 12
- 239000004014 plasticizer Substances 0.000 claims abstract description 11
- 239000004094 surface-active agent Substances 0.000 claims abstract description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 239000011248 coating agent Substances 0.000 claims description 14
- 238000000576 coating method Methods 0.000 claims description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 13
- 239000011162 core material Substances 0.000 claims description 13
- 239000000945 filler Substances 0.000 claims description 13
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- 229950005770 hyprolose Drugs 0.000 claims description 13
- 239000000080 wetting agent Substances 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 10
- 239000002702 enteric coating Substances 0.000 claims description 10
- 238000009505 enteric coating Methods 0.000 claims description 10
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 10
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000004925 Acrylic resin Substances 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 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
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 7
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 7
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 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 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 6
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- 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 description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
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- 235000002906 tartaric acid Nutrition 0.000 claims description 4
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- -1 acetic acid hydroxypropyl methylcellulose succinyl ester Chemical class 0.000 claims description 3
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 2
- 229920002494 Zein Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
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- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
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- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical class CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical group O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
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- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 claims description 2
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- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an enteric-coated azithromycin preparation and its preparing process, which comprises effective dosage of azithromycin or medicinal excipient, wheein the medicinal excipient include surface active agent, bulking agent, crumbling agent, lubricating agent, moistening agent or binding agent, intestine solution dressing material and plasticizer.
Description
Technical field
The present invention relates to a kind of Azithromycin enteric casing preparation and preparation method thereof.
Technical background
Azithromycin is the new generation derivant of erythromycin, also be 15 yuan of unique in such medicine macrocyclic antibiotics, have has a broad antifungal spectrum, act on characteristics strong, long half time, be widely used in the microbial respiratory tract of the various sensitivities of treatment, skin, soft tissue and urogenital infections clinically, determined curative effect, untoward reaction is few.Because azithromycin is unstable in gastric juice, almost there was not original shape to exist in 10 minutes in the simulated gastric fluid (pH=1.3); According to another bibliographical information, behind the oral azithromycin, be degraded to the amount of taking off the cladinose azithromycin and be about about 15% of dosage, and behind the azithromycin of intravenous injection Isodose, take off the cladinose azithromycin the quantity not sufficient dosage 0.5%, further proved the destruction of gastric acid to azithromycin, cause the bioavailability of azithromycin common oral preparation lower, bibliographical information only is between 37～46%, thereby has influenced the clinical efficacy of azithromycin.But the enteric coated preparation of conventional method preparation, because azithromycin is an alkalescence, water solublity is poor again, the dissolving in intestinal, release become the restraining factors of drug absorption.
Summary of the invention
The object of the present invention is to provide a kind of enteric coated preparation that makes azithromycin dissolve release fast at enteral.
The present invention relates to a kind of Azithromycin enteric casing preparation, comprising principal agent azithromycin or its officinal salt and the pharmaceutical excipient of effective dose.
The azithromycin officinal salt is meant the addition salts of azithromycin and certain unrestricted acid, and the non-limiting acid that can mention has hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, acetic acid, acetone acid, malonic acid, lactic acid, succinic acid, fumaric acid, tartaric acid, maleic acid, citric acid, lactobionic acid, gluconic acid, oxalic acid, malic acid, Aspartic Acid, methanesulfonic acid etc.
Pharmaceutically acceptable excipient comprises surfactant, filler, disintegrating agent, lubricant, wetting agent or binding agent, enteric-coating material, plasticizer.
Various main materials and auxiliary materials weight shares prescription in the total amount shared ratio as follows:
A, principal agent 10～70%
B, surfactant 0.2～10%
C, filler 10～70%
D, disintegrating agent 5～35%
E, lubricant 0.5～5%
F, wetting agent or binding agent 1～10%
G, enteric-coating material 3～30%
H, plasticizer 0.1～10%
Surfactant is selected from sodium lauryl sulphate, Stepanol MG, poloxamer or tween 80.
Filler is selected from microcrystalline Cellulose, starch, amylum pregelatinisatum, lactose, dextrin, mannitol, sucrose or hyprolose, or the combination of above two or more material.
Disintegrating agent is selected from hyprolose, carboxymethylstach sodium, polyvinylpolypyrrolidone or cross-linking sodium carboxymethyl cellulose, or the combination of above two or more material.
Lubricant can be selected from Pulvis Talci, magnesium stearate or micropowder silica gel, or the combination of above two or more material.
The optional water of wetting agent or binding agent, ethanol, starch slurry, polyvidone and various cellulose family.
Above-mentioned enteric-coating material also can substitute with hollow enteric hard capsule.
Enteric-coating material is selected from polyacrylic resin, acrylic resin, hydroxypropylmethyl cellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), acetic acid hydroxypropyl methylcellulose succinyl ester (HPMCPAS), ethyl cellulose (EC), zein, Lac or diketopiperazine polymer, or the combination of above two or more material.
Plasticizer is selected from Polyethylene Glycol or diethyl phthalate class, can improve the film property of enteric material.
The Azithromycin enteric casing preparation preparation method comprises preparation core material, preparation coating solution, three steps of preparation enteric coated preparation:
Preparation core material: pass through the grinding technics salify with azithromycin and acid; or be crude drug directly with the salt of azithromycin; add filler, part disintegrating agent; an amount of wetting agent of adding or binding agent prepare granule or micropill behind the mix homogeneously; after the drying with disintegrating agent and the dried particles or the micropill mix homogeneously of remainder; the qualified back of the inspection of semifinished product adds lubricant, tabletting behind the mixing.
The preparation coating solution: enteric material that will a kind of or combination in any and plasticizer with dissolve with ethanol solution after, mix homogeneously, adjustment proper viscosity.
The preparation enteric coated preparation:
Press the preparation of core material, the sheet that presses is weighed in the rearmounted coating pan, limit spray coating solution, the limit blowing hot-air obtains enteric coated tablet.
Press the preparation of core material, the granule for preparing or micropill are weighed in the rearmounted coating pan, limit spray coating solution, the limit blowing hot-air obtains enteric coated particles, and the common hard capsule of packing into promptly gets enteric coated capsule; The enteric hard capsule of maybe granule, the micropill that prepare directly being packed into gets final product.
The enteric coated preparation of azithromycin of the present invention has produced good result, not disintegrate in 2 hours under one's belt, enter the granule that the rapid disintegrate of enteral becomes azithromycin, the addition salts of known azithromycin has identical biological nature and antibacterial activity with azithromycin, because its fine solubility in intestinal, can increase dissolving, release in the azithromycin intestinal greatly, thereby accelerate to absorb, improve its bioavailability.
In order to investigate enteric effect of the present invention, we study according to Chinese Pharmacopoeia two appendix XD second methods of version (two) in 2000 drug release determination method:
Get this product, the photograph Chinese Pharmacopoeia is a solvent with the hydrochloric acid solution 900ml of 0.1mol/L, and rotating speed is that per minute 100 changes, and operation in the 2nd hour, changes sample in another container that fills phosphate buffer (pH6.8) 900ml in accordance with the law, measures with method.Respectively in hydrochloric acid solution 1 hour, 2 hours and change phosphate buffer over to after to get solution in 45 minutes and 60 minutes an amount of, filter, subsequent filtrate is as need testing solution; Other gets 10 of this product (grain), porphyrize, and precision takes by weighing in right amount (being equivalent to the heavy or average loading amount of average sheet approximately), it is an amount of to add above-mentioned buffer by labelled amount, and jolting makes the abundant stripping of azithromycin, and be diluted to the solution that contains azithromycin 139ug among every 1ml, and filter, get subsequent filtrate solution in contrast.Precision is measured need testing solution and each 2ml of contrast solution, put in the tool plug test tube, accurate above-mentioned solvent 3ml, jolting, accurate again sulfuric acid solution (75 → 100) 5ml that adds of adding, shake up, placed 30 minutes, and be cooled to room temperature, according to spectrophotography, strong point at 482nm is measured trap respectively, presses the stripping quantity of the ratio calculation every (grain) of both traps.
The embodiment sample is the stripping quantity testing result in hydrochloric acid and phosphate buffer
Dissolution medium 0.1mol/L HCl phosphate buffer pH6.8
Dissolution time 60 minutes 120 minutes 165 minutes 180 minutes
Embodiment 1 1.5 1.3 98.3 97.1
Embodiment 2 0.7 1.7 95.6 98.2
Embodiment 3 2.0 2.7 96.1 100.6
Embodiment 4 0.9 1.8 99.4 100.4
Result of the test shows, the enteric coated preparation of azithromycin, have significant enteric characteristics: in 0.1mol/LHCl solution, almost do not discharge azithromycin in 2 hours, in the solution of phosphate buffer pH6.8,45 minutes then stripping reach more than 95%, thereby avoided the destruction of sour environment to azithromycin, can bring into play drug effect better.
For further checking, the curative effect of Azithromycin enteric casing preparation is divided into 2 groups with 24 healthy dogs, and the intersection medication gives Azithromycin enteric sheet and azithromycin ordinary tablet by embodiment 2 preparations.The concentration of azithromycin in the different blood plasma is constantly drawn blood drug level-time graph after the administration of employing microbial method mensuration.According to blood drug level-time data, adopt trapezoidal method to calculate the AUC value.The result shows: press bioavailability increase by 24% (P＜0.05) of the enteric coatel tablets of embodiment 2 preparations than ordinary tablet, thereby proved the advantage place of this enteric coated preparation.
The specific embodiment
Azithromycin enteric casing preparation main materials and auxiliary materials weight share of the present invention prescription in the total amount shared preferred proportion as follows:
A, principal agent 15～65%
B, surfactant 0.5～7%
C, filler 15～60%
D, disintegrating agent 8～30%
E, lubricant 0.8～4%
F, wetting agent or binding agent 2～8%
G, enteric coating layer 5～26%
H, plasticizer 0.5～6%
The preferred azithromycin of principal agent wherein; The surfactant preferably sodium dodecyl sulfate; Filler preferably microcrystalline cellulose or lactose; Preferred hyprolose of disintegrating agent or carboxymethylstach sodium; The preferred magnesium stearate of lubricant; Preferred polyvidone of wetting agent or binding agent or ethanol liquid; Enteric coating layer optimization polypropylene acid resin II number; The preferred polyethylene glycol 6000 of plasticizer.
Embodiment 1: be the enteric coatel tablets of raw material with the azithromycin
(1) core material
Azithromycin dihydrochloride 250g (in azithromycin) 50%
Sodium lauryl sulphate 10g 2%
Lactose 100g 20%
Hyprolose 70g 14%
Polyvinylpolypyrrolidone 20g 4%
95% ethanol is an amount of
Magnesium stearate 6g 1.2%
Make 1000
(2) coating solution
Ethyl cellulose 30g 6%
Polyethylene glycol 6000 14g 2.8%
95% ethanol 1000ml
Took by weighing azithromycin dihydrochloride, filler, the part disintegrating agent of 80 mesh sieves by recipe quantity; add an amount of 10% polyvidone behind the mix homogeneously, granulate, after the drying with the disintegrating agent and the dried particles mix homogeneously of remainder; the qualified back of the inspection of semifinished product adds lubricant, tabletting behind the mixing.
The plain sheet that makes is weighed in the rearmounted coating pan, limit spray coating solution, the limit blowing hot-air obtains enteric coated tablet.
Embodiment 2: azithromycin and sour salifiable enteric coatel tablets
The composition weight percentage by weight
(1) core material
Azithromycin 125g 31.25%
Citric acid 15g 3.75%
Sodium lauryl sulphate 6g 1.5%
Microcrystalline Cellulose 100g 25%
Hyprolose 70g 17.5%
Carboxymethylstach sodium 30g 7.5%
Magnesium stearate 4g 1%
Polyvinylpolypyrrolidone 10g 2.5%
95% ethanol is an amount of
Make 1000
(2) coating solution:
Polyacrylic resin II 30g 7.5%
Cetomacrogol 1000 5g 1.25%
Polyethylene glycol 6000 5g 1.25%
95% ethanol 1000ml
After citric acid pulverized, 95% alcoholic solution to the acid that adds 20 times of amounts was dissolved fully, slowly adds azithromycin then, added while grinding, all dissolved until azithromycin transparently to see the bottom and do not have granule.40 ℃ of drying under reduced pressure must be consolidated shape salt, cross 100 mesh sieves 3 times.Add filler, disintegrating agent, add an amount of wetting agent or binding agent granulation behind the mix homogeneously, drying, the qualified back of the inspection of semifinished product adds lubricant, tabletting behind the mixing.
The plain sheet that just makes is weighed in the rearmounted coating pan, limit spray coating solution, and the limit blowing hot-air obtains enteric coated tablet.
Embodiment 3: Azithromycin enteric capsule
The composition weight percentage by weight
(1) core material:
Azithromycin 250g 38.46%
Tartaric acid 26g 4%
Tween 80 13g 2%
Microcrystalline Cellulose 195g 30%
Hyprolose 62g 9.54%
Polyvinylpolypyrrolidone 26g 4%
95% ethanol is an amount of
Make 1000
(2) coating solution:
Polyacrylic resin II 65g 10%
Cetomacrogol 1000 6.5g 1%
Polyethylene glycol 6000 6.5g 1%
95% ethanol 1500ml
By the described granule that makes of preparation method, weigh rearmounted coating pan or fluidizing fluid-bed in, limit spray coating solution, the limit blowing hot-air obtains enteric coated particles.
Enteric coated particles fill capsule is promptly got Azithromycin enteric capsule.
Embodiment 4: Azithromycin enteric capsule
Core material:
The composition weight percentage by weight
Malic acid azithromycin 250g (in azithromycin) 62.5%
Sodium lauryl sulphate 4g 1%
Lactose 100g 25%
Hyprolose 46g 11.5%
95% ethanol is an amount of
Make 1000
Take by weighing principal agent, filler, disintegrating agent by recipe quantity, add an amount of wetting agent behind the mix homogeneously and granulate, drying, the enteric coated capsule of packing into after the inspection of semifinished product is qualified promptly gets Azithromycin enteric capsule.
Embodiment 5: be the enteric coatel tablets of raw material with the azithromycin
The composition weight percentage by weight
(1) core material
Azithromycin dihydrochloride 125g (in azithromycin) 20%
Sodium lauryl sulphate 10g 1.6%
Microcrystalline Cellulose 250g 40%
Hyprolose 67.5g 10.8%
Polyvinylpolypyrrolidone 25g 4%
95% ethanol is an amount of
Magnesium stearate 10g 1.6%
Make 1000
(2) coating solution:
Polyacrylic resin II 125g 20%
Polyethylene glycol 6000 12.5g 2%
95% ethanol 2000ml
Concrete preparation method is with embodiment 1.
Embodiment 6: azithromycin and sour salifiable enteric coatel tablets
The composition weight percentage by weight
(1) core material
Azithromycin 250g 47.62%
Citric acid 25g 4.76%
Sodium lauryl sulphate 10.5g 2%
Microcrystalline Cellulose 92.5g 17.62%
Hyprolose 42g 8%
Magnesium stearate 10.5g 2%
Polyvinylpolypyrrolidone 31.5g 6%
95% ethanol is an amount of
Make 1000
(2) coating solution:
Ethyl cellulose 52.5g 10%
Polyethylene glycol 6000 10.5g 2%
95% ethanol 1000ml
Preparation method is with embodiment 2.
Embodiment 7: Azithromycin enteric capsule
The composition weight percentage by weight
(1) core material:
Azithromycin 125g 25%
Tartaric acid 15g 3%
Sodium lauryl sulphate 10g 2%
Microcrystalline Cellulose 150g 30%
Hyprolose 105g 21%
95% ethanol is an amount of
Make 1000
(2) coating solution:
Polyacrylic resin II 75g 15%
Cetomacrogol 1000 10g 2%
Polyethylene glycol 6000 10g 2%
95% ethanol 1000ml
Concrete preparation method is with embodiment 3.
Embodiment 8: Azithromycin enteric capsule
The composition weight percentage by weight
Core material:
Malic acid azithromycin 125g (in azithromycin) 45.45%
Sodium lauryl sulphate 11g 4%
Lactose 99g 36%
Hyprolose 40g 14.55%
95% ethanol is an amount of
Make 1000
Concrete preparation method is with embodiment 4.
Claims (12)
1, a kind of Azithromycin enteric casing preparation is comprising principal agent azithromycin or its officinal salt and the pharmaceutical excipient of effective dose.
2, according to the described Azithromycin enteric casing preparation of claim 1, it is characterized in that the azithromycin officinal salt is meant the addition salts of azithromycin and certain unrestricted acid, the non-limiting acid that can mention has hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, acetic acid, acetone acid, malonic acid, lactic acid, succinic acid, fumaric acid, tartaric acid, maleic acid, citric acid, lactobionic acid, gluconic acid, oxalic acid, malic acid, Aspartic Acid, methanesulfonic acid.
3,, it is characterized in that pharmaceutically acceptable excipient comprises surfactant, filler, disintegrating agent, lubricant, wetting agent or binding agent, enteric-coating material, plasticizer according to claim 1 or 2 described Azithromycin enteric casing preparations.
Various main materials and auxiliary materials weight shares prescription in the total amount shared ratio as follows:
A, principal agent 10～70%
B, surfactant 0.2～10%
C, filler 10～70%
D, disintegrating agent 5～35%
E, lubricant 0.5～5%
F, wetting agent or binding agent 1～10%
G, enteric-coating material 3～30%
H, plasticizer 0.1～10%.
4, according to the described Azithromycin enteric casing preparation of claim 3, it is characterized in that the main materials and auxiliary materials weight share prescription in the total amount shared ratio as follows:
A, principal agent 15～65%
B, surfactant 0.5～7%
C, filler 15～60%
D, disintegrating agent 8～30%
E, lubricant 0.8～4%
F, wetting agent or binding agent 2～8%
G, enteric coating layer 5～26%
H, plasticizer 0.5～6%.
5,, it is characterized in that surfactant is selected from sodium lauryl sulphate, Stepanol MG, poloxamer or tween 80 according to the described Azithromycin enteric casing preparation of claim 3.
6, according to the described Azithromycin enteric casing preparation of claim 3, it is characterized in that filler is selected from microcrystalline Cellulose, starch, amylum pregelatinisatum, lactose, dextrin, mannitol, sucrose or hyprolose, or the combination of above two or more material.
7, according to the described Azithromycin enteric casing preparation of claim 3, it is characterized in that disintegrating agent is selected from hyprolose, carboxymethylstach sodium, polyvinylpolypyrrolidone or cross-linking sodium carboxymethyl cellulose, or the combination of above two or more material.
8, according to the described Azithromycin enteric casing preparation of claim 3, it is characterized in that lubricant is selected from Pulvis Talci, magnesium stearate or micropowder silica gel, or the combination of above two or more material.
9,, it is characterized in that the optional water of wetting agent or binding agent, ethanol, starch slurry, polyvidone or various cellulose family according to the described Azithromycin enteric casing preparation of claim 3.
10, according to the described Azithromycin enteric casing preparation of claim 3, it is characterized in that enteric-coating material is selected from polyacrylic resin, acrylic resin, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, acetic acid hydroxypropyl methylcellulose succinyl ester, ethyl cellulose, zein, Lac or diketopiperazine polymer, or the combination of above two or more material.
11,, it is characterized in that plasticizer is selected from Polyethylene Glycol or diethyl phthalate class according to the described Azithromycin enteric casing preparation of claim 3.
12, a kind of preparation method of Azithromycin enteric casing preparation is characterized in that comprising preparation core material, preparation coating solution, three steps of preparation enteric coated preparation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410036629 CN1264520C (en) | 2004-04-23 | 2004-04-23 | Enteric-coated azithromycin preparation and its preparing process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410036629 CN1264520C (en) | 2004-04-23 | 2004-04-23 | Enteric-coated azithromycin preparation and its preparing process |
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| CN1264520C CN1264520C (en) | 2006-07-19 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100382805C (en) * | 2006-01-11 | 2008-04-23 | 南京工业大学 | Azithromycin enteric casing microsphere and its preparing process |
| CN101390848B (en) * | 2008-11-12 | 2010-04-21 | 浙江丽水众益药业有限公司 | Medicine composition azithromycin enteric-coated capsules |
| CN102895203A (en) * | 2012-11-02 | 2013-01-30 | 江苏鹏鹞药业有限公司 | Method for preparing azithromycin dispersible tablets |
| CN103156814A (en) * | 2011-12-09 | 2013-06-19 | 四川科伦药物研究有限公司 | Azithromycin enteric composition and preparation method |
| CN104042591A (en) * | 2014-07-03 | 2014-09-17 | 武汉武药科技有限公司 | Compound preparation comprising ketoprofen and omeprazole and preparation method thereof |
| CN110292567A (en) * | 2019-05-17 | 2019-10-01 | 北京悦康科创医药科技股份有限公司 | A kind of preparation method of azithromycin capsule |
| CN113116859A (en) * | 2021-04-12 | 2021-07-16 | 海南普利制药股份有限公司 | Azithromycin pill core coating preparation |
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2004
- 2004-04-23 CN CN 200410036629 patent/CN1264520C/en not_active Expired - Lifetime
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100382805C (en) * | 2006-01-11 | 2008-04-23 | 南京工业大学 | Azithromycin enteric casing microsphere and its preparing process |
| CN101390848B (en) * | 2008-11-12 | 2010-04-21 | 浙江丽水众益药业有限公司 | Medicine composition azithromycin enteric-coated capsules |
| CN103156814A (en) * | 2011-12-09 | 2013-06-19 | 四川科伦药物研究有限公司 | Azithromycin enteric composition and preparation method |
| CN103156814B (en) * | 2011-12-09 | 2015-11-25 | 四川科伦药物研究有限公司 | A kind of Azithromycin enteric composition and preparation method |
| CN102895203A (en) * | 2012-11-02 | 2013-01-30 | 江苏鹏鹞药业有限公司 | Method for preparing azithromycin dispersible tablets |
| CN104042591A (en) * | 2014-07-03 | 2014-09-17 | 武汉武药科技有限公司 | Compound preparation comprising ketoprofen and omeprazole and preparation method thereof |
| CN110292567A (en) * | 2019-05-17 | 2019-10-01 | 北京悦康科创医药科技股份有限公司 | A kind of preparation method of azithromycin capsule |
| CN110292567B (en) * | 2019-05-17 | 2022-02-18 | 北京悦康科创医药科技股份有限公司 | Preparation method of azithromycin capsule |
| CN113116859A (en) * | 2021-04-12 | 2021-07-16 | 海南普利制药股份有限公司 | Azithromycin pill core coating preparation |
| CN113116859B (en) * | 2021-04-12 | 2022-08-30 | 海南普利制药股份有限公司 | Azithromycin pill core coating preparation |
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| Publication number | Publication date |
|---|---|
| CN1264520C (en) | 2006-07-19 |
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