CN103156814A - Azithromycin enteric composition and preparation method - Google Patents
Azithromycin enteric composition and preparation method Download PDFInfo
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- CN103156814A CN103156814A CN2011104083387A CN201110408338A CN103156814A CN 103156814 A CN103156814 A CN 103156814A CN 2011104083387 A CN2011104083387 A CN 2011104083387A CN 201110408338 A CN201110408338 A CN 201110408338A CN 103156814 A CN103156814 A CN 103156814A
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- 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 56
- 229960004099 azithromycin Drugs 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 44
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 64
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 32
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 25
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 25
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 25
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 25
- 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 abstract description 21
- 239000008101 lactose Substances 0.000 claims abstract description 21
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 20
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 20
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 20
- 239000011734 sodium Substances 0.000 claims abstract description 20
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 20
- 239000002702 enteric coating Substances 0.000 claims abstract description 19
- 238000009505 enteric coating Methods 0.000 claims abstract description 19
- 229920002472 Starch Polymers 0.000 claims abstract description 15
- 239000008107 starch Substances 0.000 claims abstract description 15
- 235000019698 starch Nutrition 0.000 claims abstract description 15
- 229960001375 lactose Drugs 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000000576 coating method Methods 0.000 claims description 75
- 239000011248 coating agent Substances 0.000 claims description 74
- 239000000463 material Substances 0.000 claims description 54
- -1 polyethylene pyrrole Polymers 0.000 claims description 38
- 239000008187 granular material Substances 0.000 claims description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 29
- 239000000741 silica gel Substances 0.000 claims description 27
- 229910002027 silica gel Inorganic materials 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 20
- 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 19
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 19
- 229960003943 hypromellose Drugs 0.000 claims description 19
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 19
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 18
- 239000004014 plasticizer Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 17
- 230000001476 alcoholic effect Effects 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 13
- 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 13
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 13
- 238000004132 cross linking Methods 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 13
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 13
- 239000001069 triethyl citrate Substances 0.000 claims description 13
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 13
- 235000013769 triethyl citrate Nutrition 0.000 claims description 13
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 11
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 11
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 11
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 11
- 229940032147 starch Drugs 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 3
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 21
- 239000003826 tablet Substances 0.000 abstract description 14
- 230000000968 intestinal effect Effects 0.000 abstract description 13
- 239000008363 phosphate buffer Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 abstract description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 abstract description 8
- 210000004211 gastric acid Anatomy 0.000 abstract description 7
- 239000007919 dispersible tablet Substances 0.000 abstract description 6
- 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 abstract description 5
- 235000011389 fruit/vegetable juice Nutrition 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 2
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 abstract 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 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 abstract 1
- 229940083542 sodium Drugs 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 48
- 239000011162 core material Substances 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 230000001276 controlling effect Effects 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 229920000642 polymer Polymers 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000005469 granulation Methods 0.000 description 10
- 230000003179 granulation Effects 0.000 description 10
- 239000012530 fluid Substances 0.000 description 7
- 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 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003120 macrolide antibiotic agent Substances 0.000 description 4
- 229940069328 povidone Drugs 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 229960003276 erythromycin Drugs 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 241000606161 Chlamydia Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 229920003135 Eudragit® L 100-55 Polymers 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 239000006185 dispersion Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
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- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses an azithromycin enteric composition capable of rapidly dispersing and releasing medicines in intestinal tracts and a preparation method for the same. The medicine composition is composed of the following raw materials: azithromycin, lactose, microcrystalline cellulose, sodium carboxymethyl starch, hydroxypropyl methylcellulose, lauryl sodium sulphate, polyvinylpyrrolidone, magnesium stearate and the like. The preparation method for azithromycin enteric tablets disclosed by the invention comprises the steps of treating the medicines and medicinal excipients and then tabletting, and performing enteric coating on tablet cores. The azithromycin enteric composition disclosed by the invention can be greatly protected in a gastric acid condition and thus effectively protecting the medicines from the breakage of gastric acid, and can achieve the characteristics of dispersible tablets in an intestinal juice condition (phosphate buffer having a pH value of 6.8) and thus rapidly releasing the medicines in intestinal tracts and increasing bioavailability.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of Azithromycin enteric composition and method of making the same that can rapid dispersion in intestinal discharges medicine.
Background technology
Azithromycin is a kind of fifteen-membered ring macrolide antibiotics that is derived by erythromycin, and nitrogenous 15 membered ring compounds of this class have stronger alkalescence, and many gram negative bacilli are had larger activity, and concentration is higher in tissue, and Half-life in vivo is long.Have common point with erythromycin on Antibacterial Mechanism, all be combined by ribosome 50S subunit in bacterial cell, hinder antibacterial and turn the peptide process, inhibition depends on the synthesizing of protein of RNA and reaches antibacterial action.But the change due to structure, azithromycin has antimicrobial spectrum widely than erythromycin, can suppress multiple gram positive coccus, mycoplasma, chlamydia and legionella pneumophilia, especially some important gram negative bacillis such as hemophilus influenza etc. are had good antibacterial activity, made up the Macrolide deficiency poor to the haemophilus effect.Be mainly used in the transmissible disease due to respiratory tract, skin soft-tissue infection and the chlamydia due to sensitive organism.Present azithromycin is sure to occupy medicine tap in macrolide with the advantage of himself uniqueness.
Azithromycin listing dosage form is more at present, and conventional tablet, dispersible tablet, capsule, granule, dry suspension, enteric coatel tablets, injection etc. are arranged.In the recent period a large amount of research data documents show that azithromycin is unstable under gastric acid environment, 30min degraded 68% in the 0.1mol/L hydrochloric acid solution, cause bioavailability on the low side, and this class macrolide antibiotics ubiquity gastrointestinal side reaction, the discomfort such as easily cause that the patient vomits, main cause is that it is to the stimulation of stomach.Be to reduce medicine to the stimulation of stomach, and guarantee that azithromycin avoids the destruction of gastric acid, the enteric coated preparation of this medicine has become development trend.
At present the patent application of this medicament enteric-coated formulation aspect is more, domestic had Azithromycin enteric sheet and enteric coated capsule to go on the market, but such enteric coated preparation discharged slow, usually there is the interior bioavailability of body lower, relatively poor in colon position absorption, onset is the deficiency of aspect such as slowly, the invention of relevant Azithromycin enteric casing preparation patent, but still may cause bioavailability on the low side.
Patent CN1602888A (open day on April 6th, 2005) discloses Azithromycin enteric casing preparation and preparation method thereof, the method with soft just after drying the granule of conventional preparation as starting material, enteric coatedly after tabletting make enteric coatel tablets for Opadry-93018359, or with initial particles filled in enteric capsule shell, because being subjected to the impact of Opadry material and enteric capsule shell, the method may cause bioavailability too low.Patent 1569021A discloses a kind of Azithromycin enteric casing preparation and preparation method thereof; it adopts conventional material and preparation method carry out the granulation of core material or make micropill; this method can cause its release slow; particularly make micropill and make again later on enteric coated preparation; can increase the drug release process of micropill, affect drug absorption.It is untimely that the selection of its enteric material can cause medicine to arrive intestinal release later on, may cause bioavailability too low.Patent CN101991544 discloses a kind of Azithromycin enteric dry suspension and preparation method thereof; this patent is that azithromycin granule is put in coating granulator; granule is carried out carrying out enteric coating after isolation coat again, and the enteric coated particles of gained adds the mixing such as a large amount of correctivess and suspending agent and get final product.Although might improve drug release rate; accelerate drug effect and improve bioavailability; but because of the specific surface area of this technique drug particles too large; complicated process of preparation; need relatively large use coating material, and coatings protect is incomplete, has bitterness; need add a large amount of correctivess and suspending agent, have the shortcoming that medicine can not be effectively protected and dosage is larger in gastric acid.
Therefore, still need at present a kind of new Azithromycin enteric casing preparation, neither can produce stomach stimulates, the advantageous feature that can possess again dispersible tablet namely in intestinal disintegrate rapidly, absorb fast, bioavailability is high.
Summary of the invention
The object of the present invention is to provide a kind of Azithromycin enteric compositions, another purpose of the present invention is to provide a kind of preparation method of Azithromycin enteric compositions.
The present invention seeks to be achieved through the following technical solutions
The raw material of pharmaceutical composition of the present invention consists of:
Azithromycin 100 weight portion starch 0～50 weight portions
Lactose 0～30 weight portion microcrystalline Cellulose 0～70 weight portion
Carboxymethylstach sodium 0～20 weight portion cross-linking sodium carboxymethyl cellulose 0～30 weight portion
Polyvinylpolypyrrolidone 0～30 weight portion hypromellose 0～30 weight portion
Sodium lauryl sulphate 0～3 weight account polyethylene pyrrole alkane ketone 0～10 weight portion
Micropowder silica gel 0～50 weight portion magnesium stearate 0.5～5 weight portion.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 10～30 weight portion microcrystalline Cellulose 40～60 weight portions
Carboxymethylstach sodium 3～15 weight portion cross-linking sodium carboxymethyl cellulose 5～20 weight portions
Hypromellose 10～30 weight portion sodium lauryl sulphate 0.5～2.5 weight portions
The polyethylene pyrrole alkane ketone 4～10 weight portion magnesium stearate 0.5～3 weight portions.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 18～22 weight portions
Microcrystalline Cellulose 45～55 weight portion carboxymethylstach sodium 8～10 weight portions
Hypromellose 25～30 weight portion sodium lauryl sulphate 1～2 weight portions
The polyethylene pyrrole alkane ketone 6～8 weight portion magnesium stearate 1～2 weight portions.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 20 weight portions
Microcrystalline Cellulose 50 weight portion carboxymethylstach sodium 9 weight portions
Hypromellose 27.5 weight portion sodium lauryl sulphate 1.5 weight portions
The polyethylene pyrrole alkane ketone 7 weight portion magnesium stearate 1.5 weight portions.
Get the combinations thereof raw material, add conventional adjuvant, according to common process, make tablet.
Pharmaceutical composition of the present invention adds the material of following weight portion to make enteric coatel tablets:
Enteric material contains thing 10 weight portions admittedly, antiplastering aid 2～10 weight portions, plasticizer 1～7 weight portion.
The preferred weight proportioning is as follows: enteric material contains thing 10 weight portions admittedly, antiplastering aid 6 weight portions, and plasticizer 4 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 3 weight portions, plasticizer 6 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 9 weight portions, plasticizer 2 weight portions.
It is methacrylic acid and ethyl acrylate copolymer (especially strange L30D-55 or title Eudragit L100-55) or methacrylic acid and methylmethacrylate copolymer (especially strange L100) or two kinds of mixture that described enteric material contains thing admittedly.
Described antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel.
Described plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
The concrete preparation technology of medicinal composition tablets of the present invention is as follows:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 80～120 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 16～24 mesh sieves are granulated, and granule is put 50～70 ℃ of drying 2～4h, and 18～24 mesh sieves are granulated, and add 0～12 weight portion micropowder silica gel, 0～5 weight portion hypromellose and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 10%～20%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 3%～10%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 2%～12%.
The preferred preparation technology of medicinal composition tablets of the present invention is as follows:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 100 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 20 mesh sieves are granulated, and granule is put 60 ℃ of dry 3h, and 20 mesh sieves are granulated, and add 0～6 weight portion micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 15%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 6%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 5%.
Azithromycin enteric compositions of the present invention; can well be protected under the gastric acid condition, effectively protect medicine to avoid the destruction of gastric acid, and (phosphate buffer PH6.8) can reach the characteristics of dispersible tablet under the intestinal juice condition; rapid delivery of pharmaceuticals in intestinal improves bioavailability.With the Azithromycin enteric tablet that the inventive method makes, taking convenience is covered bad bitterness, increases medicine stability, can effectively protect medicine not to be subjected to stomach acids destroy in the hydrochloric acid solution of 0.1mol/L, can rapid delivery of pharmaceuticals in simulated intestinal fluid.
Following experimental example and embodiment are used for further illustrating but being not limited to the present invention.
Experimental example 1: release experiment in acid
Measure with reference to 2010 editions two ones of Chinese Pharmacopoeias (appendix XC the second method), take the hydrochloric acid solution 900ml of 0.1mol/L as dissolution medium, temperature (37 ± 0.5 ℃), rotating speed 50r/min.6 of medicinal composition tablets of the present invention getting embodiment 11 preparation are put in stripping rotor respectively and are measured, draw solution 10ml after 2h, getting subsequent filtrate adopts high performance liquid chromatography to carry out the assay of azithromycin, another precision takes the azithromycin reference substance, the solution of making 0.2mg/ml with mobile phase dilution is product liquid in contrast, measure with method, calculate release, press in the acid of Chinese Pharmacopoeia enteric coated preparation that release stipulates should be less than 10%.Its chromatographic condition is: be filler with octadecylsilane chemically bonded silica; (get the 0.05mol/L dipotassium hydrogen phosphate solution, the phosphoric acid solution with 20% is regulated pH value to 8.2)-acetonitrile (45: 55) is mobile phase with phosphate buffer; The detection wavelength is 210nm; Flow velocity: 1.0ml/min; Sample size: 20 μ l; Measurement result is: azithromycin of the present invention release after 2h in acid is 2.1%.
Experimental example 2: the release experiment in artificial enteric liquid
A, the release medium in release experiment in acid (experimental example 1) is changed into simulated intestinal fluid (phosphate buffer PH6.8), other experimental techniques remain unchanged, and investigate and contrast the release profiles of other Azithromycin enteric sheets in simulated intestinal fluid.Experimental result is as follows:
B, the release medium in release experiment in acid is changed into phosphate buffer PH7.8～8.0, and (get dipotassium hydrogen phosphate 5.59g and potassium dihydrogen phosphate 0.41g, 1000ml is made in the dilution that is dissolved in water, and get final product.), other experimental techniques remain unchanged, and investigate and contrast the release profiles of other Azithromycin enteric sheets in simulated intestinal fluid.Experimental result is as follows:
Experimental example 3: finely dispersed test in simulated intestinal fluid
Assay method with reference to the Chinese Pharmacopoeia dispersed homogeneous degree, get 6 of the medicinal composition tablets of the present invention of embodiment 11 preparation, put in the 250ml beaker, add simulated intestinal fluid (phosphate buffer PH6.8) 100ml or phosphate buffer (PH7.8～8.0) 100ml of 15～25 ℃, jolt 3min, investigate whether all disintegrate and pass through sieve No. two, and compare with commercially available enteric coatel tablets and dispersible tablet.Experimental result is as follows:
Illustrate that azithromycin of the present invention can reach the requirement of dispersible tablet under the condition of simulated intestinal fluid (phosphate buffer PH6.8) and phosphate buffer (PH7.8～8.0), than other enteric coatel tablets more can disperse, fast release thing.
Following embodiment all can realize the described effect of above-mentioned experimental example.
Embodiment 1:
Core formulation and preparation:
Azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium are crossed respectively 100 mesh sieves, mix homogeneously; Polyvidone is made 5% solution with 50% ethanol; After the soft ability of 5%PVP alcoholic solution system, 18～24 mesh sieves are granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add the magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material, antiplastering aid and plasticizer, add water and stir evenly, with the abundant homogenize 20min of high speed shear refiner, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15.9%, get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 2:
Core formulation and preparation:
Azithromycin, micropowder silica gel, microcrystalline Cellulose, carboxymethylstach sodium, polyvidone are crossed respectively 100 mesh sieves, mix homogeneously; After the 50% soft ability of alcoholic solution system, 18～24 mesh sieves are granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add the magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get in enteric material solution 500g dissolving, add triethyl citrate, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 3:
Core formulation and preparation:
100 mesh sieves are crossed respectively in azithromycin, starch, microcrystalline Cellulose, micropowder silica gel, mix homogeneously (in add micropowder silica gel 140g); After sodium lauryl sulphate was made 0.5% solution and made soft ability with it with 50% ethanol, 18～24 mesh sieves were granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add micropowder silica gel (60g) and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get in enteric material solution 500g dissolving, add triethyl citrate, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 2%.
Embodiment 4:
Core formulation and preparation:
Azithromycin, starch, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 18%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 5:
Core formulation and preparation:
Azithromycin, starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 6:
Core formulation and preparation:
Azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add the SA dibutyl ester, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 16%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 7%.
Embodiment 7:
Core formulation and preparation:
100 mesh sieves, mix homogeneously are crossed respectively in azithromycin, starch, carboxymethylstach sodium, sodium lauryl sulphate, micropowder silica gel; The soft ability of povidone solution system of 50% ethanol preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 16%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 6%.
Embodiment 8:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g95% ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 9:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material, antiplastering aid and plasticizer, add water and stir evenly, with the abundant homogenize 20min of high speed shear refiner, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15.9%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 10:
Core formulation and preparation:
Get azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose and cross respectively 100 mesh sieves, mix homogeneously; The soft ability of sodium dodecyl sulfate solution system of 50% ethanol preparation 0.75%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, polyvinylpolypyrrolidone and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in the 500g solvent, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 10%.
Embodiment 11:
Core formulation and preparation:
Get azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, hypromellose and cross respectively 100 mesh sieves, mix homogeneously; Get recipe quantity polyethylene pyrrole alkane ketone and sodium lauryl sulphate be added in 50% alcoholic solution of 140ml as the soft ability of binding agent system, softly just granulate with 20 mesh sieves, granule is put 60 ℃ of dry 3h, 20 mesh sieve granulate add the magnesium stearate mixing, tabletting namely gets label.
Enteric coating:
Get enteric material and put in the 500g solvent, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min; Two liquid are mixed, fully stir evenly; Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15%; Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 12:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 65 ℃ of dry 4h just with 18 mesh sieves granulations, and 18 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g95% ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 13:
Core formulation and preparation:
Azithromycin, starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 55 ℃ of dry 2h just with 24 mesh sieves granulations, and 24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Claims (11)
1. Azithromycin enteric compositions is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion starch 0～50 weight portions
Lactose 0～30 weight portion microcrystalline Cellulose 0～70 weight portion
Carboxymethylstach sodium 0～20 weight portion cross-linking sodium carboxymethyl cellulose 0～30 weight portion
Polyvinylpolypyrrolidone 0～30 weight portion hypromellose 0～30 weight portion
Sodium lauryl sulphate 0～3 weight account polyethylene pyrrole alkane ketone 0～10 weight portion
Micropowder silica gel 0～50 weight portion magnesium stearate 0.5～5 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 10～30 weight portion microcrystalline Cellulose 40～60 weight portions
Carboxymethylstach sodium 3～15 weight portion cross-linking sodium carboxymethyl cellulose 5～20 weight portions
Hypromellose 10～30 weight portion sodium lauryl sulphate 0.5～2.5 weight portions
The polyethylene pyrrole alkane ketone 4～10 weight portion magnesium stearate 0.5～3 weight portions.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 18～22 weight portions
Microcrystalline Cellulose 45～55 weight portion carboxymethylstach sodium 8～10 weight portions
Hypromellose 25～30 weight portion sodium lauryl sulphate 1～2 weight portions
The polyethylene pyrrole alkane ketone 6～8 weight portion magnesium stearate 1～2 weight portions.
4. pharmaceutical composition as claimed in claim 3 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 20 weight portions
Microcrystalline Cellulose 50 weight portion carboxymethylstach sodium 9 weight portions
Hypromellose 27.5 weight portion sodium lauryl sulphate 1.5 weight portions
The polyethylene pyrrole alkane ketone 7 weight portion magnesium stearate 1.5 weight portions.
5. as claim 1,2,3 or 4 described pharmaceutical compositions, it is characterized in that said composition adds conventional adjuvant, makes tablet according to common process.
6. as claim 1,2,3 or 4 described pharmaceutical compositions, it is characterized in that this pharmaceutical composition also adds enteric material admittedly to contain thing 10 weight portions, antiplastering aid 2～10 weight portions, plasticizer 1～7 weight portion.
7. pharmaceutical composition as claimed in claim 6, it is characterized in that this pharmaceutical composition also adds enteric material admittedly to contain thing 10 weight portions, antiplastering aid 6 weight portions, plasticizer 4 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 3 weight portions, plasticizer 6 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 9 weight portions, plasticizer 2 weight portions.
8. pharmaceutical composition as claimed in claim 6, is characterized in that it is methacrylic acid and ethyl acrylate copolymer or methacrylic acid and methylmethacrylate copolymer or two kinds of mixture that described enteric material contains thing admittedly; Antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel; Plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
9. pharmaceutical composition as claimed in claim 7, is characterized in that it is methacrylic acid and ethyl acrylate copolymer or methacrylic acid and methylmethacrylate copolymer or two kinds of mixture that described enteric material contains thing admittedly; Antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel; Plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
10. as the preparation method of claim 7,8 or 9 described medicinal composition tablets, it is characterized in that the method is:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 80～120 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 16～24 mesh sieves are granulated, and granule is put 50～70 ℃ of drying 2～4h, and 18～24 mesh sieves are granulated, and add 0～12 weight portion micropowder silica gel, 0～5 weight portion hypromellose and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 10%～20%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 3%～10%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 2%～12%.
11. the preparation method of medicinal composition tablets as claimed in claim 10 is characterized in that the method is:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 100 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 20 mesh sieves are granulated, and granule is put 60 ℃ of dry 3h, and 20 mesh sieves are granulated, and add 0～6 weight portion micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 15%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 6%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 5%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
| CN107582538A (en) * | 2017-06-01 | 2018-01-16 | 合肥远志医药科技开发有限公司 | Azithromycin capsule and preparation method thereof |
| CN110882228A (en) * | 2019-11-29 | 2020-03-17 | 南京禾瀚医药科技有限公司 | Epiputidine enteric-coated preparation |
| CN111228233A (en) * | 2020-03-11 | 2020-06-05 | 正大青春宝药业有限公司 | Coating composition for preparing perhexiline enteric-coated tablets and application thereof |
| CN112656774A (en) * | 2020-12-26 | 2021-04-16 | 海南葫芦娃药业集团股份有限公司 | Azithromycin enteric capsule and preparation method thereof |
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| CN1569021A (en) * | 2004-04-23 | 2005-01-26 | 石家庄制药集团欧意药业有限公司 | Enteric-coated azithromycin preparation and its preparing process |
| CN1602888A (en) * | 2004-07-30 | 2005-04-06 | 浙江大德药业集团有限公司 | Azithromycin enteric casing preparation and its preparing process |
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| CN1569021A (en) * | 2004-04-23 | 2005-01-26 | 石家庄制药集团欧意药业有限公司 | Enteric-coated azithromycin preparation and its preparing process |
| CN1602888A (en) * | 2004-07-30 | 2005-04-06 | 浙江大德药业集团有限公司 | Azithromycin enteric casing preparation and its preparing process |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107582538A (en) * | 2017-06-01 | 2018-01-16 | 合肥远志医药科技开发有限公司 | Azithromycin capsule and preparation method thereof |
| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
| CN110882228A (en) * | 2019-11-29 | 2020-03-17 | 南京禾瀚医药科技有限公司 | Epiputidine enteric-coated preparation |
| CN111228233A (en) * | 2020-03-11 | 2020-06-05 | 正大青春宝药业有限公司 | Coating composition for preparing perhexiline enteric-coated tablets and application thereof |
| CN112656774A (en) * | 2020-12-26 | 2021-04-16 | 海南葫芦娃药业集团股份有限公司 | Azithromycin enteric capsule and preparation method thereof |
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