CN103961336B - A kind of aceclofenac enteric-coated pellet capsule and preparation method thereof - Google Patents
A kind of aceclofenac enteric-coated pellet capsule and preparation method thereof Download PDFInfo
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- CN103961336B CN103961336B CN201410218927.2A CN201410218927A CN103961336B CN 103961336 B CN103961336 B CN 103961336B CN 201410218927 A CN201410218927 A CN 201410218927A CN 103961336 B CN103961336 B CN 103961336B
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- enteric
- aceclofenac
- celphere
- micropill
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- MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 title claims abstract description 69
- 229960004420 aceclofenac Drugs 0.000 title claims abstract description 69
- 239000002775 capsule Substances 0.000 title claims abstract description 50
- 239000008188 pellet Substances 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 45
- 239000010410 layer Substances 0.000 claims description 39
- 238000007789 sealing Methods 0.000 claims description 29
- 239000002702 enteric coating Substances 0.000 claims description 26
- 238000009505 enteric coating Methods 0.000 claims description 26
- 239000003995 emulsifying agent Substances 0.000 claims description 24
- 238000002156 mixing Methods 0.000 claims description 18
- 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 17
- 229930006000 Sucrose Natural products 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 17
- 239000005720 sucrose Substances 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 239000011230 binding agent Substances 0.000 claims description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 15
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 15
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 15
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 15
- 229920002472 Starch Polymers 0.000 claims description 14
- 239000012055 enteric layer Substances 0.000 claims description 14
- 239000008107 starch Substances 0.000 claims description 14
- 235000019698 starch Nutrition 0.000 claims description 14
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 11
- 229960003943 hypromellose Drugs 0.000 claims description 11
- 238000005119 centrifugation Methods 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- -1 sealing coat Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000004945 emulsification Methods 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 235000010603 pastilles Nutrition 0.000 claims description 5
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical group CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 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 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 235000010956 sodium stearoyl-2-lactylate Nutrition 0.000 claims description 2
- KNYAZNABVSEZDS-UHFFFAOYSA-M sodium;2-octadecanoyloxypropanoate Chemical group [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C([O-])=O KNYAZNABVSEZDS-UHFFFAOYSA-M 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 description 8
- 239000000314 lubricant Substances 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000004014 plasticizer Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000337 buffer salt Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 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
- CBSIDWPDNYMJHQ-UHFFFAOYSA-N C1(=CC=CC=C1)CC(=O)C(C(=O)O)OCC Chemical compound C1(=CC=CC=C1)CC(=O)C(C(=O)O)OCC CBSIDWPDNYMJHQ-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 201000002661 Spondylitis Diseases 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
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a kind of aceclofenac enteric-coated pellet capsule and preparation method thereof, belong to technical field of medicine.This aceclofenac enteric-coated pellet capsule is filled in capsule shells by aceclofenac enteric coated micropill and is prepared from; it is simple that it has preparation method, and labor intensity is low, is applicable to suitability for industrialized production; be conducive to environmental conservation, little to the GI irritation of patient, the advantages such as the stability that bioavailability is high, good.
Description
Technical field
The present invention relates to a kind of pellet capsule and preparation method thereof, particularly relate to a kind of aceclofenac enteric-coated pellet capsule and preparation method thereof, belong to technical field of medicine.
Background technology
Aceclofenac chemistry 2-((2 by name, 6-Dichlorobenzene base) amino) phenylacetyl ethoxyacetic acid, a kind of novel, potent antipyretic, analgesia, antiinflammatory non-steroidal drug, be applicable to treatment rheumatic arthritis, rheumatoid arthritis, osteoarthritis, spondylitis etc. clinically, be also applicable to pain that various disease causes and heating.Its mechanism of action mainly by suppressing cyclooxygenase activity, thus makes prostaglandin synthesize minimizing.
Aceclofenac is compared to diclofenac, and ketone ibuprofen, indomethacin are more safe and effective.But it is slightly soluble in water, easily cause dyspepsia, the untoward reaction such as abdominal discomfort, zest is produced to gastrointestinal tract.In order to better play its therapeutical effect, reduce untoward reaction to the impact of patient, Chinese invention patent application CN102824312A discloses the prior art of aceclofenac enteric coated micropill particulate composition and preparation method thereof, in the disclosure in this patent, aceclofenac and corresponding adjuvant are prepared into particle diameter greatly about the ball core of 1.0 ~ 1.2mm by it, wrap up coating material again, but this technology is at the rounding property of micropill, the uniformity of content, the stability of quality, the aspect existing problems such as the reproducibility of technique, therefore, the pharmaceutical dosage form that exploitation aceclofenac is new seems particularly urgent and important.
Summary of the invention
Technical problem to be solved by this invention is that the defect overcoming prior art provides a kind of aceclofenac enteric-coated pellet capsule, and this pellet capsule has good rounding property, uniformity and stability.
Technical problem of the present invention is realized by following technical scheme.
A kind of aceclofenac enteric-coated pellet capsule, it is filled in capsule shells by aceclofenac enteric coated micropill and is prepared from, and described aceclofenac enteric coated micropill is made up of celphere and the coatings be wrapped in outside celphere; The particle diameter of described celphere is 297 ~ 840 μm; Consisting of of described coatings is followed successively by main medicament layer, sealing coat, enteric layer from inside to outside; Described celphere, main medicament layer, sealing coat, enteric layer count 10 ~ 30:30 ~ 50:1 ~ 10:30 ~ 60 by weight.
Above-mentioned aceclofenac enteric-coated pellet capsule, described celphere is composed of the following components:
Sucrose 30 ~ 100%
Starch 0 ~ 70%
Microcrystalline Cellulose 0 ~ 70%.
Above-mentioned aceclofenac enteric-coated pellet capsule, described main medicament layer is composed of the following components:
Wherein, described diluent is selected from the combination of one or more in starch, microcrystalline Cellulose, sucrose, lactose, preferably microcrystalline cellulose; Described disintegrating agent is selected from one or both the combination in cross-linking sodium carboxymethyl cellulose, PVPP, HP-β-CD, preferred HP-β-CD; Described emulsifying agent is selected from sodium stearoyl lactate, CSL or diacetyl tartarate monoglyceride.
Above-mentioned aceclofenac enteric-coated pellet capsule, described sealing coat is composed of the following components:
Lubricant 30 ~ 90%
Binding agent 1 ~ 20%;
Wherein, described lubricant is selected from the combination of one or more in Pulvis Talci, magnesium stearate, micropowder silica gel, preferred micropowder silica gel; Described binding agent is selected from the combination of one or more in hydroxypropyl emthylcellulose E3, HPMC E5, hydroxypropyl emthylcellulose E30, PVPK30, sucrose, preferred HPMC E5.
Above-mentioned aceclofenac enteric-coated pellet capsule, described enteric layer is composed of the following components:
Wherein, described enteric-coating material is selected from especially strange L30D-55, L100-55 or polyacrylic acid resin emulsion, preferably especially strange L30D-55; Described plasticizer is selected from lecithin; Described stabilizing agent is selected from sodium hydroxide; Described antiplastering aid is selected from magnesium stearate.
The first optimal way of the present invention, described aceclofenac enteric-coated pellet capsule, it is made up of the component of following weight portion:
A, celphere
Sucrose 35
Starch 20
Microcrystalline Cellulose 15
B, main medicament layer
C, sealing coat
Micropowder silica gel 18
Hypromellose E52
D, enteric coating layer
The second optimal way of the present invention, described aceclofenac enteric-coated pellet capsule, it is made up of the component of following weight portion:
A, celphere
Sucrose 35
Microcrystalline Cellulose 35
B, main medicament layer
C, sealing coat
Micropowder silica gel 12
Hypromellose E53
D, enteric coating layer
The third optimal way of the present invention, described aceclofenac enteric-coated pellet capsule, it is made up of the component of following weight portion:
A, celphere
Sucrose 30
Starch 50
B, main medicament layer
C, sealing coat
Micropowder silica gel 20
Hypromellose E54
D, enteric coating layer
Prepare a method for above-mentioned aceclofenac enteric-coated pellet capsule, comprise the following steps:
(1) celphere preparation: prepare 50% aqueous sucrose solution as binding agent, prepare celphere with the starch and/or microcrystalline Cellulose that take recipe quantity, for subsequent use;
(2) wrap up main medicament layer: the emulsifying agent taking recipe quantity, is mixed with the emulsifier aqueous solution of 5%, be 20 DEG C in temperature, under mixing speed is 400 ~ 1200rad/min condition, adds the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution; Take the aceclofenac of recipe quantity, diluent fully mix after powder, mixing and emulsifying agent solution, pastille powder are wrapped on the celphere of step (1) gained by centrifugation, the medicine carrying micropill of main medicament layer must be wrapped up, for subsequent use;
(3) wrap up sealing coat: prepare 5% binder aqueous solution, after the lubricant taking recipe quantity is mixed homogeneously with binder aqueous solution, by centrifugation by the medicine carrying micropill of step (2) gained parcel sealing coat, it is for subsequent use that gained isolates micropill;
(4) enteric layer is wrapped up: take recipe quantity enteric-coating material, plasticizer and/or stabilizing agent, antiplastering aid, preparation obtains enteric coating liquid, by centrifugal for the isolation micropill of step (3) gained parcel enteric coating liquid, obtained enteric coated micropill, for subsequent use;
(5) to press standard quantity encapsulated for step (4) gained enteric coated micropill, obtains aceclofenac enteric-coated pellet capsule of the present invention.
Aceclofenac enteric-coated pellet capsule of the present invention, main medicament layer containing principal agent aceclofenac is wrapped in outside celphere, wrapping up sealing coat, enteric layer successively, particle diameter due to celphere is 297 ~ 840 μm, compared to the ball core of particle diameter at 1.0 ~ 1.2mm, the rounding property of micropill more can be ensured; Because first principal agent aceclofenac will be dissolved in main medicament layer solution, then row parcel, so compared to directly principal agent aceclofenac and adjuvant being made medicine carrying micropill, the homogeneity of principal agent aceclofenac content more can be ensured; Owing to having wrapped up sealing coat between main medicament layer and enteric layer, directly contact with enteric layer compared to principal agent, more can ensure the stability of medicine.In addition, aceclofenac enteric-coated pellet capsule of the present invention, although active component is same as the prior art, but formula adjuvant used and proportioning, preparation method are different, this prior art that is not both never provides enlightenment, is also those skilled in the art can not draw without creative work.From the general general knowledge of formulation art, want by reducing several adjuvant of the prior art, replace other several adjuvant again to reach and be originally just not easy with the same or analogous technique effect of former pharmaceutical preparation, aceclofenac enteric-coated pellet capsule of the present invention and the formula of prior art have so large different still more, therefore, aceclofenac enteric-coated pellet capsule more of the present invention has outstanding substantive distinguishing features and significant progress.In addition, the present invention is in main medicament layer technique, by disintegrating agent emulsifying in advance, again with principal agent aceclofenac, the mixing such as diluent, particularly at the emulsifier aqueous solution being mixed with 5%, it is 20 DEG C in temperature, mixing speed is under 400 ~ 1200rad/min condition, add the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution, without the need to binding agent, lubricant, opacifier etc., in addition, the specific proportioning of principal agent and other adjuvants in prescription of the present invention, make aceclofenac enteric-coated pellet capsule of the present invention stripping good, bioavailability is high, steady quality etc., save preparation cost.In a word, the aceclofenac enteric-coated pellet capsule described in this has following beneficial effect:
(1) preparation method is simple, and labor intensity is low, is applicable to suitability for industrialized production, is conducive to environmental conservation;
(2) GI irritation of aceclofenac enteric-coated pellet capsule to patient is little, and bioavailability is high;
(3) sealing coat avoids the impact on principal agent such as enteric-coating material, makes this product have good stability;
(4) celphere, main medicament layer, sealing coat adopt centrifugal seed-coating machine technology of preparing to ensure that the rounding property of this product, uniformity, decrease the consumption of enteric-coating material, reduce production cost.
(5) micropill encapsulated technology loading amount is controlled, and different size facilitates patient to take, quantitative good.
Detailed description of the invention
Below by detailed description of the invention, the invention will be further described, but just understand the present invention for helping, and professional and technical personnel in the field realized or uses the present invention, not forming any restriction to the present invention.
The preparation of embodiment 1 aceclofenac enteric-coated pellet capsule of the present invention
Prescription its be made up of the component of following weight portion (unit: mg):
A, celphere
Sucrose 35
Starch 20
Microcrystalline Cellulose 15
B, main medicament layer
C, sealing coat
Micropowder silica gel 18
Hypromellose E52
D, enteric coating layer
Preparation method:
(1) celphere preparation: prepare 50% aqueous sucrose solution as binding agent, prepare celphere with the starch and/or microcrystalline Cellulose that take recipe quantity, for subsequent use;
(2) wrap up main medicament layer: the emulsifying agent taking recipe quantity, is mixed with the emulsifier aqueous solution of 5%, be 20 DEG C in temperature, under mixing speed is 400 ~ 1200rad/min condition, adds the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution; Take the aceclofenac of recipe quantity, diluent fully mix after powder, mixing and emulsifying agent solution, pastille powder are wrapped on the celphere of step (1) gained by centrifugation, the medicine carrying micropill of main medicament layer must be wrapped up, for subsequent use;
(3) wrap up sealing coat: prepare 5% binder aqueous solution, after the lubricant taking recipe quantity is mixed homogeneously with binder aqueous solution, by centrifugation by the medicine carrying micropill of step (2) gained parcel sealing coat, it is for subsequent use that gained isolates micropill;
(4) enteric layer is wrapped up: take recipe quantity enteric-coating material, plasticizer and/or stabilizing agent, antiplastering aid, preparation obtains enteric coating liquid, by centrifugal for the isolation micropill of step (3) gained parcel enteric coating liquid, obtained enteric coated micropill, for subsequent use;
(5) to press standard quantity encapsulated for step (4) gained enteric coated micropill, obtains aceclofenac enteric-coated pellet capsule of the present invention.
The preparation of embodiment 2 aceclofenac enteric-coated pellet capsule of the present invention
Prescription its be made up of the component of following weight portion (unit: mg):
A, celphere
Sucrose 35
Microcrystalline Cellulose 35
B, main medicament layer
C, sealing coat
Micropowder silica gel 12
Hypromellose E53
D, enteric coating layer
Preparation method:
(1) celphere preparation: prepare 50% aqueous sucrose solution as binding agent, prepare celphere with the starch and/or microcrystalline Cellulose that take recipe quantity, for subsequent use;
(2) wrap up main medicament layer: the emulsifying agent taking recipe quantity, is mixed with the emulsifier aqueous solution of 5%, be 20 DEG C in temperature, under mixing speed is 400 ~ 1200rad/min condition, adds the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution; Take the aceclofenac of recipe quantity, diluent fully mix after powder, mixing and emulsifying agent solution, pastille powder are wrapped on the celphere of step (1) gained by centrifugation, the medicine carrying micropill of main medicament layer must be wrapped up, for subsequent use;
(3) wrap up sealing coat: prepare 5% binder aqueous solution, after the lubricant taking recipe quantity is mixed homogeneously with binder aqueous solution, by centrifugation by the medicine carrying micropill of step (2) gained parcel sealing coat, it is for subsequent use that gained isolates micropill;
(4) enteric layer is wrapped up: take recipe quantity enteric-coating material, plasticizer and/or stabilizing agent, antiplastering aid, preparation obtains enteric coating liquid, by centrifugal for the isolation micropill of step (3) gained parcel enteric coating liquid, obtained enteric coated micropill, for subsequent use;
(5) to press standard quantity encapsulated for step (4) gained enteric coated micropill, obtains aceclofenac enteric-coated pellet capsule of the present invention.
The preparation of embodiment 3 aceclofenac enteric-coated pellet capsule of the present invention
Prescription its be made up of the component of following weight portion (unit: mg):
A, celphere
Sucrose 30
Starch 50
B, main medicament layer
Diacetyl tartarate monoglyceride 10
C, sealing coat
Micropowder silica gel 20
Hypromellose E54
D, enteric coating layer
Preparation method:
(1) celphere preparation: prepare 50% aqueous sucrose solution as binding agent, prepare celphere with the starch and/or microcrystalline Cellulose that take recipe quantity, for subsequent use;
(2) wrap up main medicament layer: the emulsifying agent taking recipe quantity, is mixed with the emulsifier aqueous solution of 5%, be 20 DEG C in temperature, under mixing speed is 400 ~ 1200rad/min condition, adds the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution; Take the aceclofenac of recipe quantity, diluent fully mix after powder, mixing and emulsifying agent solution, pastille powder are wrapped on the celphere of step (1) gained by centrifugation, the medicine carrying micropill of main medicament layer must be wrapped up, for subsequent use;
(3) wrap up sealing coat: prepare 5% binder aqueous solution, after the lubricant taking recipe quantity is mixed homogeneously with binder aqueous solution, by centrifugation by the medicine carrying micropill of step (2) gained parcel sealing coat, it is for subsequent use that gained isolates micropill;
(4) enteric layer is wrapped up: take recipe quantity enteric-coating material, plasticizer and/or stabilizing agent, antiplastering aid, preparation obtains enteric coating liquid, by centrifugal for the isolation micropill of step (3) gained parcel enteric coating liquid, obtained enteric coated micropill, for subsequent use;
(5) to press standard quantity encapsulated for step (4) gained enteric coated micropill, obtains aceclofenac enteric-coated pellet capsule of the present invention.
The evaluation of embodiment 4 homogeneity
Through inspection, the aceclofenac enteric-coated pellet capsule content that the embodiment of the present invention 1 ~ 3 provides is all in the limit of regulation, the RSD value of 6 pellet capsule content is less than 2%, it is good that product criticizes interior homogeneity, compared to the numerical value of about prior art RSD4.0%, more can ensure the homogeneity of content, more can ensure the curative effect of clinical application.
Embodiment 5 estimation of stability
One, influence factor's test
Influence factor's test is carried out to the aceclofenac enteric-coated pellet capsule obtained by embodiment 1 to 3, be placed in uncovered glass drying oven respectively, in illumination (4500Lx), 60 DEG C, place 10 days under RH90% condition, investigate 0 day and the index such as micropill character, release, content, related substance of 10 days, its stability result is as follows:
Two, accelerated test
Accelerated test is carried out to the aceclofenac enteric-coated pellet capsule obtained by embodiment 1 to 3, by commercially available dummy packages, in 40 DEG C, place 6 months under RH75% condition, investigate 1 month, 2 months, 3 months, the index such as micropill character, release, content, related substance at 6 the end of month, its stability result is as follows:
Three, long term test
Long term test is carried out to the aceclofenac enteric-coated pellet capsule obtained by embodiment 1 to 3, by commercially available dummy packages, in 25 DEG C, place 12 months under RH60% condition, investigate 3 months, 6 months, 9 months, the index such as micropill character, release, content, related substance at 12 the end of month, its stability result is as follows:
The result of combined influence factorial experiments, accelerated test and long term test is known, the aceclofenac enteric-coated pellet capsule obtained by the embodiment of the present invention 1 ~ 3, and the character of its product, release, content, related substance are without significant change.Detected by release in release, buffer salt in acid, visible stripping hardly in acid, and stripping is good in buffer salt, the quality stability of aceclofenac enteric-coated pellet capsule within the effect phase obtained by the embodiment of the present invention 1 ~ 3 can be proved fully, can ensure that within the effect phase, take aceclofenac enteric-coated pellet capsule of the present invention not easily causes dyspepsia, the untoward reaction such as abdominal discomfort, avoid producing zest to gastrointestinal tract.In addition, in total impurities, no matter influence factor's test, accelerated test, or long term test, it is only about 0.3%, and about 0.9% lower compared to prior art is a lot, and therefore aceclofenac enteric-coated pellet capsule of the present invention more can ensure the safety and effectiveness of product.
Above-described embodiment is only for illustrating technical conceive of the present invention and advantage; the present invention also can have other variation; as well known to the skilled person; above-described embodiment only plays the exemplary role in foregoing invention protection domain; for those of ordinary skills; in the protection domain that the present invention limits, also have a lot of conventional deformation and other embodiment, these distortion and embodiment are all by within the protection domain that awaits the reply in the present invention.
Claims (4)
1. an aceclofenac enteric-coated pellet capsule, it is filled in capsule shells by aceclofenac enteric coated micropill and is prepared from, and it is characterized in that, described aceclofenac enteric coated micropill is made up of celphere and the coatings be wrapped in outside celphere; The particle diameter of described celphere is 297 ~ 840 μm; Consisting of of described coatings is followed successively by main medicament layer, sealing coat, enteric layer from inside to outside; Described aceclofenac enteric coated micropill is made up of the component of following weight portion:
A, celphere
Sucrose 35
Starch 20
Microcrystalline Cellulose 15
B, main medicament layer
C, sealing coat
Micropowder silica gel 18
Hypromellose E52
D, enteric coating layer
2. an aceclofenac enteric-coated pellet capsule, it is filled in capsule shells by aceclofenac enteric coated micropill and is prepared from, and it is characterized in that, described aceclofenac enteric coated micropill is made up of celphere and the coatings be wrapped in outside celphere; The particle diameter of described celphere is 297 ~ 840 μm; Consisting of of described coatings is followed successively by main medicament layer, sealing coat, enteric layer from inside to outside; Described aceclofenac enteric coated micropill is made up of the component of following weight portion:
A, celphere
Sucrose 35
Microcrystalline Cellulose 35
B, main medicament layer
C, sealing coat
Micropowder silica gel 12
Hypromellose E53
D, enteric coating layer
3. an aceclofenac enteric-coated pellet capsule, it is filled in capsule shells by aceclofenac enteric coated micropill and is prepared from, and it is characterized in that, described aceclofenac enteric coated micropill is made up of celphere and the coatings be wrapped in outside celphere; The particle diameter of described celphere is 297 ~ 840 μm; Consisting of of described coatings is followed successively by main medicament layer, sealing coat, enteric layer from inside to outside; Described aceclofenac enteric coated micropill is made up of the component of following weight portion:
A, celphere
Sucrose 30
Starch 50
B, main medicament layer
C, sealing coat
Micropowder silica gel 20
Hypromellose E54
D, enteric coating layer
4. prepare a method for the aceclofenac enteric-coated pellet capsule as described in claim as arbitrary in claims 1 to 3, it is characterized in that, comprise the following steps:
(1) celphere preparation: prepare 50% aqueous sucrose solution as binding agent, prepare celphere with the starch and/or microcrystalline Cellulose that take recipe quantity, for subsequent use;
(2) wrap up main medicament layer: the emulsifying agent taking recipe quantity, is mixed with the emulsifier aqueous solution of 5%, be 20 DEG C in temperature, under mixing speed is 400 ~ 1200rad/min condition, adds the disintegrating agent of recipe quantity, pre-emulsification 0.5h, obtain mixing and emulsifying agent solution; Take the aceclofenac of recipe quantity, diluent fully mix after powder, mixing and emulsifying agent solution, pastille powder are wrapped on the celphere of step (1) gained by centrifugation, the medicine carrying micropill of main medicament layer must be wrapped up, for subsequent use, wherein, described emulsifying agent is selected from sodium stearoyl lactate, CSL or diacetyl tartarate monoglyceride; Described disintegrating agent is selected from HP-β-CD; Described diluent is selected from the combination of one or more in starch, microcrystalline Cellulose, lactose;
(3) sealing coat is wrapped up: prepare 5% hypromellose E5 aqueous solution, take the micropowder silica gel of recipe quantity and hypromellose E5 aqueous solution evenly after, by centrifugation by the medicine carrying micropill of step (2) gained parcel sealing coat, gained isolation micropill is for subsequent use;
(4) wrap up enteric layer: take recipe quantity L30D-55, lecithin, sodium hydroxide, magnesium stearate, preparation obtains enteric coating liquid, by centrifugal for the isolation micropill of step (3) gained parcel enteric coating liquid, and obtained enteric coated micropill, for subsequent use;
(5) to press standard quantity encapsulated for step (4) gained enteric coated micropill, obtains aceclofenac enteric-coated pellet capsule.
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| CN201410218927.2A CN103961336B (en) | 2014-05-23 | 2014-05-23 | A kind of aceclofenac enteric-coated pellet capsule and preparation method thereof |
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| CN201410218927.2A CN103961336B (en) | 2014-05-23 | 2014-05-23 | A kind of aceclofenac enteric-coated pellet capsule and preparation method thereof |
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| CN103961336B true CN103961336B (en) | 2016-02-10 |
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| CN102670521B (en) * | 2012-05-18 | 2014-05-21 | 珠海润都制药股份有限公司 | Esomeprazole magnesium enteric-coated pellet and preparation method thereof |
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