CN105250233A - Dexibuprofen enteric-coated and sustained-release tablet and preparation method thereof - Google Patents
Dexibuprofen enteric-coated and sustained-release tablet and preparation method thereof Download PDFInfo
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- CN105250233A CN105250233A CN201510728542.5A CN201510728542A CN105250233A CN 105250233 A CN105250233 A CN 105250233A CN 201510728542 A CN201510728542 A CN 201510728542A CN 105250233 A CN105250233 A CN 105250233A
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- enteric
- ibuprofen
- sustained
- release
- coating
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- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 title claims abstract description 131
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- 229960003428 dexibuprofen Drugs 0.000 title claims abstract description 30
- 239000002662 enteric coated tablet Substances 0.000 title abstract 6
- 239000011248 coating agent Substances 0.000 claims abstract description 66
- 238000000576 coating method Methods 0.000 claims abstract description 66
- 230000000694 effects Effects 0.000 claims abstract description 27
- 239000003826 tablet Substances 0.000 claims abstract description 19
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 238000013268 sustained release Methods 0.000 claims abstract description 9
- 239000012730 sustained-release form Substances 0.000 claims abstract description 9
- 239000008187 granular material Substances 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 32
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 28
- 239000002702 enteric coating Substances 0.000 claims description 24
- 238000009505 enteric coating Methods 0.000 claims description 24
- 239000000463 material Substances 0.000 claims description 21
- -1 hydroxypropyl Chemical group 0.000 claims description 20
- 238000007789 sealing Methods 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 17
- 239000000741 silica gel Substances 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 14
- 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 12
- 239000008101 lactose Substances 0.000 claims description 12
- 239000004925 Acrylic resin Substances 0.000 claims description 11
- 229920000178 Acrylic resin Polymers 0.000 claims description 11
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- 239000011159 matrix material Substances 0.000 claims description 7
- 235000021355 Stearic acid Nutrition 0.000 claims description 4
- 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 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- 239000008117 stearic acid Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- 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 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
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- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 23
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 21
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 21
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 21
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- 238000005516 engineering process Methods 0.000 description 15
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
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- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 7
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 229960001680 ibuprofen Drugs 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 238000007908 dry granulation Methods 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 5
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000013022 formulation composition Substances 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 239000001069 triethyl citrate Substances 0.000 description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 5
- 235000013769 triethyl citrate Nutrition 0.000 description 5
- 230000004584 weight gain Effects 0.000 description 5
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- 239000008280 blood Substances 0.000 description 3
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- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 239000012055 enteric layer Substances 0.000 description 3
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- 229960003943 hypromellose Drugs 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
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- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
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- 239000000706 filtrate Substances 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- TUZRJGVLAFMQEK-LARVRRBISA-N hydron (2S)-2-[4-(2-methylpropyl)phenyl]propanoate (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1.CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 TUZRJGVLAFMQEK-LARVRRBISA-N 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
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- 238000004811 liquid chromatography Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
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- 208000006820 Arthralgia Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 208000007613 Shoulder Pain Diseases 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000007605 air drying Methods 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
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- 206010003246 arthritis Diseases 0.000 description 1
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- 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
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- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
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- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a dexibuprofen enteric-coated and sustained-release tablet. The dexibuprofen enteric-coated and sustained-release tablet comprises a tablet core with a sustained release effect and a coating for coating the table core, wherein the tablet core is prepared from the following components: 70-90 parts of dexibuprofen, 10-30 parts of sustained-release skeleton stabilizer, 0-10 parts of filler, 0.2-1.5 parts of lubricating agent and 0.2-1.5 parts of flow aid; the effective quantity of active ingredient dexibuprofen takes more than 70% of the weight of table core. The invention has the advantages of excellent formula, reliable preparation process and easiness in industrial production; the prepared enteric-coated and sustained-release tablet in-vitro dissolution experiment shows: the releasing rate of gastric juice in 2 hours is smaller than 10%, which meets the requirements; the releasing rate of intestinal juice in 2 hours is 25-55%, the accumulative releasing rate in 4 hours is 50-80%, the accumulative releasing rate in 8 hours is more than 80%, and therefore, the releasing effect is excellent. The dexibuprofen enteric-coated and sustained-release tablet has effects of undissolving in the stomach and slowly releasing in the intestines so as to prevent irritation to the stomach and prolong the in-vivo releasing time of medicines simultaneously; the dexibuprofen enteric-coated and sustained-release tablet facilitates absorption to human bodies and has lasting effects.
Description
Technical field
The invention belongs to medicine preparation field, be specifically related to a kind of (S)-ibuprofen enteric-coated sustained-release tablet and preparation method thereof.
Background technology
Active component: (S)-ibuprofen
Chemical name: (2S)-2-[4-(2-methyl-propyl) phenyl] propanoic acid
English name: Dexibuprofen
English language Chemical title: S (+)-2 (4-isobutylphenyl) propionicacid
Molecular formula: C
13h
18o
2
Molecular weight: 206.28
Structural formula:
Ibuprofen is as the NSAID (non-steroidal anti-inflammatory drug) used clinically for many years, its safety and effectiveness are confirmed fully, by suppress prostaglandin synthesis and produce antipyretic, analgesia and antiinflammatory action, be mainly used in rheumatism and rheumatoid arthritis, also can be used for general antipyretic-antalgic, is the first ladder medicine of pain ladder medication.
(S)-ibuprofen is the S isomer of ibuprofen, compared with ibuprofen, take its dosage of 2/3rds and just can obtain identical curative effect, and side effect is less, in efficacy and saferry advantageously; Be mainly used in (1) at present clinically and alleviate the acute attack stage of various chronic arthritis or the arthralgia condition of illness of persistence such as rheumatoid arthritis, osteoarthritis, SpA, gouty arthritis, rheumatic arthritis, without etiological treatment and the effect controlling the course of disease; (2) non-arthrogenous various soft tissue rheumatism pain is treated, as injury pain after shoulder pain, key vaginitis, bursitis, myalgia and motion etc.; (3) acute light, moderate pain as; After Post operation, wound, old damage after, primary dysmenorrhea, toothache, headache etc.; (4) refrigeration function is had to the heating of adult and child.
The dosage form of the current domestic listing of (S)-ibuprofen has conventional tablet, capsule and suspension oral formulations and suppositories for rectal etc., common oral preparation multiple dosing every day, patient adaptability is poor, and blood drug level is not steady, occur peak valley phenomenon, the paddy summit that high medicine is dense produces corresponding toxic and side effects; Suppositories for rectal uses inconvenient, is used for pediatric patient.
The domestic slow releasing preparation research report having (S)-ibuprofen, does not all go public at present.Chinese patent CN102160855B and CN102293759A all relates to Dex-ibuprofen sustained release tablets and preparation method, and the preparation of CN102160855B slow releasing tablet adopts and is made up of immediate release section and slow-released part and magnesium stearate; CN102293759A preparation technology all relates to the preparation method of the direct mixed pressuring plate technique of powder, and obviously due to (S)-ibuprofen poor fluidity, the direct mixed pressuring plate technique of powder is not suitable for industrialized great production.In prescription proportioning involved by above-mentioned two patents use adjuvant amount large, active component (S)-ibuprofen weight proportion shared by tablet is lower, and sheet is great, not easily swallows; And equal not acid resistances.
Although (S)-ibuprofen safety is higher, as nonsteroidal anti-inflammatory drug, it is not sneezed at the zest of stomach.Be all the aspirin of nonsteroidal anti-inflammatory drug, naproxen and diclofenac etc. and all have enteric coated preparation, object is in order to avoid the zest to stomach.
Dexibuprofen sustained-release preparation of the present invention is enteric-coated sustained-release tablet, and this slow releasing tablet not only has stomach juice-resistant effect, possesses again the effect at enteral slow releasing.Therefore (S)-ibuprofen not only can be prevented the zest of stomach, again there is slow release effect, lasting medicine; Lamellar body is gently little, is easy to swallow.Said preparation has obviously different and intrinsic advantage compared with the various preparation of current reported (S)-ibuprofen, and technical requirement is higher; Product clinical safety is better, and patient adaptability is strong.The preparation method of (S)-ibuprofen enteric-coated sustained-release tablet of the present invention is pelletizing press sheet technique, is easy to suitability for industrialized production, high with (S)-ibuprofen weight proportion in time slice, more than 70%, greatly reduce supplementary product consumption, reduce sheet weight, accomplish the perfect adaptation of active component (S)-ibuprofen and adjuvant.
Summary of the invention
For existing (S)-ibuprofen preparation and relevant report, the object of the present invention is to provide a kind of (S)-ibuprofen enteric-coated sustained-release tablet and preparation method thereof, the (S)-ibuprofen enteric-coated sustained-release tablet obtained not only reduces the administration number of times of (S)-ibuprofen, reduces (S)-ibuprofen ordinary preparation and takes the rear toxic and side effects caused because paddy peak is too high; (S)-ibuprofen can be prevented the zest of stomach simultaneously.
A kind of (S)-ibuprofen enteric-coated sustained-release tablet of the present invention, comprises the coating of label and the parcel label with slow release effect; The described label with slow release effect comprises 70 ~ 90 parts of (S)-ibuprofens, 10 ~ 30 parts of sustained-release matrix agent, 0 ~ 10 part of filler, 0.2 ~ 1.5 part of lubricant and 0.2 ~ 1.5 part of fluidizer; Wherein the active component (S)-ibuprofen of effective dose accounts for more than 70% of label weight, and preferably 75% ~ 85%.
Described parcel label coating comprises sealing coat coating and enteric coating; Sealing coat coating amount is 0 ~ 5wt% of label weight; Enteric coating amount is 1 ~ 10wt% of label weight.
Described skeleton agent is selected from one or both mixture in hydroxypropyl emthylcellulose, Hydroxypropylcelliloxe, ethyl cellulose; The preferred hydroxypropyl emthylcellulose of skeleton agent.
The weight portion of preferred hydroxypropyl emthylcellulose in slow release label is 10 ~ 20 parts.
The agent of preferred hydroxypropyl emthylcellulose skeleton is hypromellose K100LV and HPMC K4M mixture; Wherein hypromellose K100LV is 5 ~ 10 weight portions, and hypromellose K4 is 8 ~ 15 weight portions.
Described filler selects one or both mixture in lactose, calcium hydrogen phosphate, microcrystalline Cellulose etc., preferred lactose.
Described lubricant is selected from one in magnesium stearate, stearic acid or two kinds, is preferably magnesium stearate; Fluidizer be selected from micropowder silica gel, Pulvis Talci and in one or two or more kinds, preferred micropowder silica gel.
Coating material:
The main material of enteric coating one of to adopt in enteric acrylic resin or cellulose acetate-phthalate.Preferred enteric crylic acid resin material.Enteric coating gain in weight is 1% ~ 10% of label, preferably 6% ~ 8%.
Described enteric acrylic resin is methacrylic acid-ethyl acrylate copolymer.
At enteric coated front bag one deck sealing coat coating, the main material of sealing coat coating one of to adopt in hydroxypropyl emthylcellulose, Hydroxypropylcelliloxe.Preferred hydroxypropyl emthylcellulose.Sealing coat coating weight gain amount is no more than 5% of label weight.
The invention provides the preparation method one of described (S)-ibuprofen enteric slow release tablet preparation, comprise the following steps:
(1) (S)-ibuprofen, sustained-release matrix agent and filler mix homogeneously are obtained mixed material, with the alcoholic solution of 75 ~ 95wt%, said mixture is made soft material, to granulate to obtain 18 ~ 30 object wet granulars, be placed in not dry higher than equipment at 55 DEG C of temperature, within drying time 5h, obtain the dry granule of 18 ~ 30 object;
(2) mixed homogeneously with lubricant and fluidizer by dry granule, tabletting, obtains Dex-ibuprofen sustained release tablets core;
(3) Dex-ibuprofen sustained release tablets label is placed in coating pan, uses enteric material coating solution to carry out coating, make sheet increase weight 1 ~ 10%, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
Present invention also offers the preparation method two of described (S)-ibuprofen enteric slow release tablet preparation, comprise the following steps:
(1) (S)-ibuprofen, sustained-release matrix agent and filler mix homogeneously are obtained mixture, use dry granulating machine, said mixture is granulated, after crossing 18 ~ 30 eye mesh screens, obtain dry granule;
(2) mixed homogeneously with lubricant and fluidizer by dry granule, tabletting, obtains Dex-ibuprofen sustained release tablets core;
(3) Dex-ibuprofen sustained release tablets core is placed in coating pan, uses enteric material coating solution to carry out coating, make label increase weight 1 ~ 10%, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
Gained (S)-ibuprofen enteric-coated sustained-release tablet in the acid medium of about pH1.0 2 hours releases lower than 2%, again in pH6.8(or pH7.2) in medium, accumulation 1h release is greater than 10%, accumulation 2h release is greater than 25%, accumulation 3h release is greater than 35%, accumulation 4h release is greater than 50%, and accumulation 6h release is greater than 65%, and accumulation 8h release is greater than 80%.
To sum up, the (S)-ibuprofen enteric-coated sustained-release tablet according to prescription provided by the present invention and preparation method gained discharges hardly in gastric acid, arrives enteral and just understands slow releasing, and progressively release of active ingredients.Thus reach: one is almost stop the zest of (S)-ibuprofen to stomach, and two is guarantee that (S)-ibuprofen slowly absorbs in vivo and plays dauer effect.
Elegant formulations is that active component and adjuvant reach perfect adaptation by suitable preparation technology, is convenient to Clinical practice, makes patients benefit.Active component (S)-ibuprofen has certain zest to stomach, and its ordinary preparation is not only irritant to stomach after taking, and causes side effect because of the dense Gao Gu peak of medicine, and patient adaptability is poor.The present invention stops its zest to stomach by preparing (S)-ibuprofen enteric-coated sustained-release tablet; Medicine is slowly absorbed by intestinal and reduces the too high toxic and side effects caused in medicine dense paddy peak; In addition, increase the adaptability of patient medication because number of times is taken in minimizing, compared with the dosage form of all reports of current (S)-ibuprofen, have significantly different and intrinsic advantage, technical requirement is higher; Product clinical safety is better, and patient adaptability is strong.。
Medicine has extremely strong particularity: dosage form of the same race, its prescription of the medicine of different cultivars and preparation method different, there is no general prescription and preparation method, enteric-coated sustained-release tablet as a kind of newtype drug dosage form, both at home and abroad successfully develop kind few.The character of (S)-ibuprofen enteric-coated sustained-release tablet of the present invention abundant binding activities composition (S)-ibuprofen and adjuvant characteristic, active component (S)-ibuprofen in weight ratio shared by label up to more than 70%, under the prerequisite keeping the effective dosage of active component, label not only has excellent slow release effect, and accomplish that lamellar body is gently little, be easy to swallow; Label and casing (or adding contagion gown) perfect adaptation, guarantee selecting the enteric-coated sustained-release tablet within the scope of casing (or adding contagion gown) weightening finish to discharge hardly in gastric acid, and at enteral, there is slow release effect, reach the effect of lasting medicine, there is self good characteristic.
Accompanying drawing explanation
Fig. 1 is (S)-ibuprofen enteric-coated sustained-release tablet release curve prepared by the embodiment of the present invention 2;
Fig. 2 is (S)-ibuprofen enteric-coated sustained-release tablet release curve prepared by the embodiment of the present invention 3;
Fig. 3 is (S)-ibuprofen enteric-coated sustained-release tablet release curve prepared by the embodiment of the present invention 4;
Fig. 4 is (S)-ibuprofen enteric-coated sustained-release tablet release curve prepared by the embodiment of the present invention 5.
detailed description of the invention:
As a kind of concrete preferred embodiment of the present invention, each component composition of described Dex-ibuprofen sustained release tablets is specially:
Slow release label weight portion:
(S)-ibuprofen 70-90 part
Skeleton agent 10 ~ 20 parts
Filler 0 ~ 10 part
Lubricant 0.2 ~ 1.5 part
Fluidizer 0.2 ~ 1.5 part
Coating material:
Sealing coat clothing, the amount of sealing coat coating is 0 ~ 5% of label weight;
Enteric coating, the amount of enteric coating is 6% ~ 8% of label weight.
preparation method is preferably wet granule compression tablet preparation technology
1, wet granulation technology step:
(1) (S)-ibuprofen crossed at least 80 mesh sieves, then fully mix homogeneously with hydroxypropyl methylcellulose (K4M) and hydroxypropyl methylcellulose (K100LV) and the lactose that may use;
(2) 75% ~ 95% appropriate alcoholic solution of above-mentioned material is prepared soft material, 18 ~ 30 object wet granulars of granulating to obtain;
(3) be placed in by wet granular not higher than at 55 DEG C of temperature, forced air drying, take out in 3 ~ 5h, measure moisture, pellet moisture is kept for no more 3%, and granulate obtains the dry granule of 18 ~ 30;
(4) stearic acid and the differential silica gel of 80 mesh sieves was added to dry granule, mix homogeneously;
(5) tabletting, obtains Dex-ibuprofen sustained release tablets core.
(6) prepare enteric coating solution bag casing (or adding with low-viscosity hydroxypropylmethylc,llulose configuration isolation layer solution bag contagion gown) with enteric-coating material crylic acid resin (as Eudragit L30D-55), obtain (S)-ibuprofen enteric-coated sustained-release tablet.
In above-mentioned preparation method, skeleton agent is preferably hydroxypropyl methylcellulose, and wherein hydroxypropyl methylcellulose model is K4M and K100LV; Enteric-coating material preferred acrylic resins class; The preferred low-viscosity hydroxypropylmethylc,llulose of sealing coat clothing material; The preferred lactose of additive; Baking temperature preferably 45 ± 5 DEG C; Granule order number preferably 24 orders.
(S)-ibuprofen enteric-coated sustained-release tablet of the present invention, can make suitable weight as required, and preferred sheet is heavily every sheet 0.35 ~ 0.55g.Every sheet is 0.30g containing active component (S)-ibuprofen.
2, dry granulation
(1) (S)-ibuprofen is crossed at least 80 mesh sieves, then with hydroxypropyl methylcellulose (K4M) and hydroxypropyl methylcellulose (K100LV), fully mix homogeneously;
(2) above-mentioned material is placed in dry granulating machine, obtained 18 ~ 30 object granules;
(3) stearic acid and the differential silica gel of 80 mesh sieves was added to above-mentioned granule, mix homogeneously;
(4) tabletting, obtains Dex-ibuprofen sustained release tablets core.
(5) with enteric-coating material crylic acid resin (as Eudragit L30D-55) coating (or adding with low-viscosity hydroxypropylmethylc,llulose configuration isolation layer solution bag contagion gown), (S)-ibuprofen enteric-coated sustained-release tablet is obtained.
In the preparation method of above-mentioned pelletizing press sheet preparation technology, skeleton agent is preferably hydroxypropyl methylcellulose, and wherein hydroxypropyl methylcellulose has two profiles number, is respectively as K4M and K100LV; Enteric-coating material preferred acrylic resins class; The preferred lactose of additive.
(S)-ibuprofen enteric-coated sustained-release tablet of the present invention, can make suitable weight as required, and preferred sheet is heavily every sheet 0.35 ~ 0.55g.Every sheet is 0.30g containing active component (S)-ibuprofen.
The present invention fully combines character and the adjuvant characteristic of active component (S)-ibuprofen, by preferably suitable skeleton agent and suitable coating material, the preparation of pelletizing press sheet technique is adopted to have slow release effect label, bag meets the enteric layers (not getting rid of bag one deck sealing coat) that weightening finish requires again, obtains (S)-ibuprofen enteric-coated sustained-release tablet.Enteric slow release tablet recipe is excellent, and reliable preparation process is easy to industrialized great production.
(S)-ibuprofen is made enteric-coated sustained-release tablet and is had better formulation properties by the present invention: discharge hardly in gastric juice medium (pH1.0); Release in pH6.8 intestinal juice medium (or pH7.2) has good elution profiles; The stability of coated rear active component (S)-ibuprofen is better.(S)-ibuprofen enteric-coated sustained-release tablet almost stops the stomach irritation that active component causes in gastric release; Excellent slow release effect effectively reduces administration number of times, can keep drug effect concentration for a long time, reach long-acting object; Decrease ordinary preparation because of the toxic and side effects caused by paddy peak height acute drug simultaneously, Clinical practice has obviously preferably.
experimental technique scheme:
Slow releasing preparation can make medicine slow releasing according to certain rules, and remain valid blood drug level in vivo by the long period for active component, thus reaches and reduce medicine number of times, reduces because too high blood drug level and Gu Fenger cause the object of untoward reaction; Improve patient compliance simultaneously and reduce administration cost.Common enteric coated preparation has the effect that stomach is insoluble and enteral dissolves rapidly, reduces medicine to the zest of stomach.NSAID (non-steroidal anti-inflammatory drug) all has stomach irritation in various degree, as the (S)-ibuprofen of NSAID (non-steroidal anti-inflammatory drug), although safe and effective, but still has larger gastric zest.(S)-ibuprofen enteric-coated sustained-release tablet of the present invention have prevent medicine to the zest of stomach the effect at enteral slow releasing.
[acid resistance mensuration] gets this product, according to dissolution and release inspection technique, adopt the device of first method, with hydrochloric acid solution (pH1.0) 900ml for solvent, rotating speed is 100 turns per minute, operate in accordance with the law, get solution 10ml at 2h, through 0.45 μm of membrane filtration, get subsequent filtrate, according to visible determined by ultraviolet spectrophotometry, measure trap respectively at the wavelength place of 263nm; It is appropriate that another precision takes (S)-ibuprofen reference substance, adds above-mentioned dissolution with solvents and be quantitatively diluted to the solution about containing 0.25mg in every 1ml, being measured in the same method trap.Calculate the burst size of every sheet in the 2h time respectively.
[standard-required] every sheet should be no more than 10% of labelled amount in the burst size of 2h, meets States Pharmacopoeia specifications.
[drug release determination] gets this product, according to dissolution and release inspection technique, adopt the device of first method, first through hydrochloric acid solution medium, enter in phosphate-buffered liquid medium again, rotating speed is 100 turns per minute, operates in accordance with the law, samples in hydrochloric acid solution after 2h, in 1h, 2h, 4h in phosphate-buffered liquid medium, 6h, 8h sample, and get medium solution 10ml respectively and filter, and in process container, supplement above-mentioned medium solution 10ml in time; Get subsequent filtrate as test sample.According to visible determined by ultraviolet spectrophotometry, measure trap respectively at the wavelength place of 263nm; It is appropriate that another precision takes (S)-ibuprofen reference substance, adds above-mentioned dissolution with solvents and be quantitatively diluted to the solution about containing 0.25mg in every 1ml, being measured in the same method trap.Calculate every sheet respectively in different medium, the cumulative release amount of different time.
[standard-required] every sheet should should be 25% ~ 55%, 50% ~ 80%, more than 80% of labelled amount respectively mutually in the cumulative release amount of 2h, 4h, 8h, all should conform with the regulations.
[assay] chromatographic condition octadecylsilane chemically bonded silica is filler, with acetonitrile-0.02molL
-1potassium dihydrogen phosphate pH3.50(63: 37) be mobile phase, determined wavelength 263nm, according to high effective liquid chromatography for measuring, this product should be 90.0% ~ 110% of labelled amount containing (S)-ibuprofen.
[determination of related substances], by the chromatographic condition under this product Related substances separation item, according to high effective liquid chromatography for measuring, the single impurity of this product must not be greater than 1.0%; Total groceries must not be greater than 2.0%.
According to above-mentioned detection method, sample prepared by the embodiment of the present invention is detected, and stability test sample is investigated, embody quality of the pharmaceutical preparations reliability and stability of the present invention by data.
the preparation of embodiment 1 (S)-ibuprofen enteric-coated sustained-release tablet:
core formulation composition (g/1000 sheet:
(S)-ibuprofen 300
Hydroxypropyl emthylcellulose (HPMC)-K4M40
Hydroxypropyl emthylcellulose (HPMC)-K100LV20
Lactose 30
75% alcoholic solution Q.S
Micropowder silica gel 3
Magnesium stearate 2
enteric coating formula:
Acrylic resin (Eudragit L30D-55) 160g
Triethyl citrate 4.8g
Mono stearate glyceryl ester 2.4g
Tween 80 1.0g
Water 160g
[preparation technology's description]
(1) (S)-ibuprofen of recipe quantity is crossed 80 mesh sieves, fully mix homogeneously with hydroxypropyl methylcellulose (K4M), hydroxypropyl methylcellulose (K100LV) and lactose;
(2) add appropriate 75% ethanol and prepare soft material, cross 24 mesh sieves and obtain wet granular;
(3), after wet granular puts the dry 4h of 45 DEG C of air dry ovens, cross 24 mesh sieves and obtain dry granule;
(4) in dry granule, micropowder silica gel and the magnesium stearate of 80 mesh sieves was added, mix homogeneously;
(5) tab weighs and pressure, and tabletting obtains Dex-ibuprofen sustained release tablets core;
(6) coating solution is configured, by coating recipe quantity, configuration coating solution;
(7) with configuration coating solution, in high-efficiency coating machine, coating is carried out to label, coated tablet weightening finish 2% ~ 8%;
(8) detect, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
Carry out the test of acid resistance release to (S)-ibuprofen enteric-coated sustained-release tablet prepared by embodiment 1, result is as follows.
Table 1 (S)-ibuprofen enteric-coated sustained-release tablet acid resisting test result
the preparation of embodiment 2 Dex-ibuprofen sustained release tablets
core formulation composition (g/1000 sheet:
(S)-ibuprofen 300
Hydroxypropyl emthylcellulose (HPMC)-K4M40
Hydroxypropyl emthylcellulose (HPMC)-K100LV20
Lactose 30
75% alcoholic solution Q.S
Micropowder silica gel 3
Magnesium stearate 2
enteric coating formula:
Acrylic resin (Eudragit L30D-55) 160g
Triethyl citrate 4.8g
Mono stearate glyceryl ester 2.4g
Tween 80 1.0g
Water 160g
[preparation technology's description]
(1) (S)-ibuprofen of recipe quantity is crossed 80 mesh sieves, fully mix homogeneously with hydroxypropyl methylcellulose (K4M), hydroxypropyl methylcellulose (K100LV) and lactose;
(2) add appropriate 75% ethanol and prepare soft material, cross 24 mesh sieves and obtain wet granular;
(3), after wet granular puts the dry 4h of 45 DEG C of air dry ovens, cross 24 mesh sieves and obtain dry granule;
(4) in dry granule, micropowder silica gel and the magnesium stearate of 80 mesh sieves was added, mix homogeneously;
(5) tab weighs and pressure, and tabletting obtains Dex-ibuprofen sustained release tablets core;
(6) coating solution is configured, by coating recipe quantity, configuration coating solution;
(7) with configuration coating solution, in high-efficiency coating machine, coating is carried out to label, coated tablet weightening finish about 7%;
(8) detect, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
the preparation of embodiment 3 Dex-ibuprofen sustained release tablets
core formulation composition (g/1000 sheet):
(S)-ibuprofen 300
Hydroxypropyl emthylcellulose (HPMC)-K4M45
Hydroxypropyl emthylcellulose (HPMC)-K100LV15
85% alcoholic solution Q.S
Micropowder silica gel 3
Magnesium stearate 2
coated formula:
Acrylic resin (Eudragit L30D-55) 160g
Triethyl citrate 4.8g
Mono stearate glyceryl ester 2.4g
Tween 80 1.0g
Water 160g
[preparation technology's description]
(1) (S)-ibuprofen of recipe quantity is crossed 80 mesh sieves, fully mix homogeneously with hydroxypropyl methylcellulose (K4M), hydroxypropyl methylcellulose (K100LV);
(2) add appropriate 85% ethanol and prepare soft material, cross 24 mesh sieves and obtain wet granular;
(3), after wet granular puts the dry 4h of 45 DEG C of air dry ovens, cross 24 mesh sieves and obtain dry granule;
(4) in dry granule, micropowder silica gel and the magnesium stearate of 80 mesh sieves was added, mix homogeneously;
(5) tab weighs and pressure, and tabletting obtains Dex-ibuprofen sustained release tablets core;
(6) coating solution is configured, by coating recipe quantity, configuration coating solution;
(7) with configuration coating solution, in high-efficiency coating machine, coating is carried out to label, coated tablet weightening finish about 7%;
(8) detect, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
the preparation of embodiment 4 Dex-ibuprofen sustained release tablets
core formulation composition (g/1000 sheet):
(S)-ibuprofen 300
Hydroxypropyl emthylcellulose (HPMC)-K4M40
Hydroxypropyl emthylcellulose (HPMC)-K100LV20
Lactose 30
75% alcoholic solution Q.S
Micropowder silica gel 3
Magnesium stearate 2
coated formula:
sealing coat coated formula:
Hydroxypropyl emthylcellulose (5E) 60g
Pulvis Talci 20g
Water 520g
enteric coating formula:
Acrylic resin (Eudragit L30D-55) 160g
Triethyl citrate 4.8g
Mono stearate glyceryl ester 2.4g
Tween 80 1.0g
Water 160g
[preparation technology's description]
(1) (S)-ibuprofen of recipe quantity is crossed 80 mesh sieves, with hydroxypropyl methylcellulose (K4M), hydroxypropyl methylcellulose (K100LV) and lactose, abundant mix homogeneously;
(2) add appropriate 75% ethanol and prepare soft material, cross 24 mesh sieves and obtain wet granular;
(3), after wet granular puts the dry 4h of 45 DEG C of air dry ovens, cross 24 mesh sieves and obtain dry granule;
(4) in dry granule, micropowder silica gel and the magnesium stearate of 80 mesh sieves was added, mix homogeneously;
(5) tab weighs and pressure, and tabletting obtains Dex-ibuprofen sustained release tablets core;
(6) configuration isolation layer coating solution, by sealing coat coating recipe quantity, configuration isolation layer coating solution;
(7) enteric coating liquid is configured, by enteric coating recipe quantity, configuration enteric coating liquid;
(8) with configuration coating solution, in high-efficiency coating machine, coating is carried out to label, first bag sealing coat clothing, coating weight gain 5%, then report enteric layers, casing coating weight gain about 7%;
(9) detect, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
the preparation of embodiment 5 Dex-ibuprofen sustained release tablets
core formulation composition (g/1000 sheet):
(S)-ibuprofen 300
Hydroxypropyl emthylcellulose (HPMC)-K4M45
Hydroxypropyl emthylcellulose (HPMC)-K100LV15
85% alcoholic solution Q.S
Micropowder silica gel 3
Magnesium stearate 2
coated formula:
sealing coat coated formula:
Hydroxypropyl emthylcellulose (5E) 60g
Pulvis Talci 20g
Water 520g
enteric coating formula:
Acrylic resin (Eudragit L30D-55) 160g
Triethyl citrate 4.8g
Mono stearate glyceryl ester 2.4g
Tween 80 1.0g
Water 160g
[preparation technology's description]
(1) (S)-ibuprofen of recipe quantity is crossed 80 mesh sieves, fully mix homogeneously with hydroxypropyl methylcellulose (K4M), hydroxypropyl methylcellulose (K100LV);
(2) add appropriate 85% ethanol and prepare soft material, cross 24 mesh sieves and obtain wet granular;
(3), after wet granular puts the dry 4h of 45 DEG C of air dry ovens, cross 24 mesh sieves and obtain dry granule;
(4) in dry granule, micropowder silica gel and the magnesium stearate of 80 mesh sieves was added, mix homogeneously;
(5) tab weighs and pressure, and tabletting obtains Dex-ibuprofen sustained release tablets core;
(6) configuration isolation layer coating solution, by sealing coat coating recipe quantity, configuration isolation layer coating solution;
(7) enteric coating liquid is configured, by enteric coating recipe quantity, configuration enteric coating liquid;
(8) with configuration coating solution, in high-efficiency coating machine, coating is carried out to label, first bag sealing coat clothing, coating weight gain 5%, then report enteric layers, casing coating weight gain about 7%;
(9) detect, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
Release test is carried out to (S)-ibuprofen enteric-coated sustained-release tablet prepared by embodiment 2 ~ 5, the results are shown in Table 2 ~ 5 and Fig. 1 ~ 4.Shown by result, (S)-ibuprofen enteric-coated sustained-release tablet prepared by the present invention has slow release release profiles under good acid resistance and enteric medium, meets the requirement of clinical application completely.
Table 2 embodiment 2 release data
Table 3 embodiment 3 release data
Table 4 embodiment 4 release data
Table 5 embodiment 5 release data
stability study
[preparation process stability study]
This product preparation technology both can select dry granulation tablet forming technique, also can select wet granule compression tablet technique; Dry granulation is not owing to passing through the soft ability of system and dry run, the related substance of whole film-making process to active component (S)-ibuprofen has no significant effect, this is also the advantage place of dry granulation process, but the granule of dry granulation gained not as good as wet granulation gained granule, is namely reflected to the granule of compressibility not as good as wet granulation gained of the granule of the dry granulation in tableting processes in uniformity and mobility.For this reason, this product carries out special project investigation to the stability of wet granulation technology.The results are shown in following table:
The change of table 6 legal system grain technical process (S)-ibuprofen related substance
Raw material standard requires that left-handed ibuprofen must not cross 1.0%; Single impurity must not cross 0.3%; Except left-handed ibuprofen, must not 0.7% be crossed.Testing result meets the requirements;
the left-handed ibuprofen of standard drafted by preparation must not cross 1.0%; Single impurity must not cross 0.5%; Except left-handed ibuprofen, total impurities must not cross 1.0%.
Can be clear and definite by upper table, the related substance of wet granulation technology process to (S)-ibuprofen has no significant effect, and this product also can select the preparation technology of wet granule compression tablet.
[sample stability research]
Carry out 10,000 scale-ups to embodiment 2 prescription, prepared (S)-ibuprofen enteric-coated sustained-release tablet carries out quality testing.Carry out accelerated test (40 DEG C, RH75% ± 5%) 6 months and long term test (25 DEG C, the RH60% ± 10%) investigation of 6 months, detect the change of every quality index, the data obtained is as shown in table 7 ~ 8 simultaneously:
Table 7 accelerated test 6 months data
Table 8 long term test 6 months data
Conclusion: as can be seen from above data result, (S)-ibuprofen enteric slow release tablet quality conformance with standard requirement prepared by the present invention, and after accelerating 6 months and long-term 6 months and testing, every quality index is without significant change, all meet and draft quality standard, the sample quality describing preparation of the present invention has good stability.
Claims (10)
1. a (S)-ibuprofen enteric-coated sustained-release tablet, is characterized in that: the coating comprising label and the parcel label with slow release effect; The described label with slow release effect comprises 70 ~ 90 parts of (S)-ibuprofens, 10 ~ 30 parts of sustained-release matrix agent, 0 ~ 10 part of filler, 0.2 ~ 1.5 part of lubricant and 0.2 ~ 1.5 part of fluidizer; Wherein the active component (S)-ibuprofen of effective dose accounts for more than 70% of label weight.
2. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 1, is characterized in that: described parcel label coating comprises sealing coat coating and enteric coating; Sealing coat coating amount is 0 ~ 5wt% of label weight; Enteric coating amount is 1 ~ 10wt% of label weight.
3. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 1, is characterized in that: sustained-release matrix agent be one of in hydroxypropyl emthylcellulose, Hydroxypropylcelliloxe, ethyl cellulose or two.
4. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 1, is characterized in that: described filler one of to select in lactose, calcium hydrogen phosphate, microcrystalline Cellulose or two.
5. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 1, is characterized in that: lubricant one of to select in stearic acid, magnesium stearate or two; Fluidizer one of to select in micropowder silica gel, Pulvis Talci or two.
6. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 1, is characterized in that: the main material of enteric coating one of to adopt in enteric acrylic resin or cellulose acetate-phthalate.
7. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 2, is characterized in that: at enteric coated front bag one deck sealing coat coating, and the main material of sealing coat coating one of to adopt in hydroxypropyl emthylcellulose, Hydroxypropylcelliloxe.
8. (S)-ibuprofen enteric-coated sustained-release tablet according to claim 6, is characterized in that: described enteric acrylic resin is methacrylic acid-ethyl acrylate copolymer.
9. the preparation method of (S)-ibuprofen enteric slow release tablet preparation described in claim 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8, comprises the following steps:
(1) (S)-ibuprofen, sustained-release matrix agent and filler mix homogeneously are obtained mixed material, with the alcoholic solution of 75 ~ 95wt%, said mixture is made soft material, to granulate to obtain 18 ~ 30 object wet granulars, be placed in not dry higher than equipment at 55 DEG C of temperature, within drying time 5h, obtain the dry granule of 18 ~ 30 object;
(2) mixed homogeneously with lubricant and fluidizer by dry granule, tabletting, obtains Dex-ibuprofen sustained release tablets core;
(3) Dex-ibuprofen sustained release tablets label is placed in coating pan, uses enteric material coating solution to carry out coating, make sheet increase weight 1 ~ 10%, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
10. the preparation method of (S)-ibuprofen enteric slow release tablet preparation described in claim 1 or 2 or 3 or 4 or 5 or 7 or 8, comprises the following steps:
(1) (S)-ibuprofen, sustained-release matrix agent and filler mix homogeneously are obtained mixture, use dry granulating machine, said mixture is granulated, after crossing 18 ~ 30 eye mesh screens, obtain dry granule;
(2) mixed homogeneously with lubricant and fluidizer by dry granule, tabletting, obtains Dex-ibuprofen sustained release tablets core;
(3) Dex-ibuprofen sustained release tablets core is placed in coating pan, uses enteric material coating solution to carry out coating, make label increase weight 1 ~ 10%, obtain (S)-ibuprofen enteric-coated sustained-release tablet.
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| CN117257740A (en) * | 2022-06-13 | 2023-12-22 | 海南大学 | Dexibuprofen enteric microsphere and preparation method thereof |
| WO2024140984A1 (en) * | 2022-12-30 | 2024-07-04 | 越洋医药开发(广州)有限公司 | Controlled release tablet of loxoprofen sodium, preparation method, and use |
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| WO2013154512A1 (en) * | 2012-04-13 | 2013-10-17 | Mahmut Bilgic | Pharmaceutical formulations comprising dexibuprofen |
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| CN102293759A (en) * | 2011-09-05 | 2011-12-28 | 南京海陵中药制药工艺技术研究有限公司 | Dextral ibuprofen sustained release tablet preparation and preparation method thereof |
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| CN117257740A (en) * | 2022-06-13 | 2023-12-22 | 海南大学 | Dexibuprofen enteric microsphere and preparation method thereof |
| WO2024140984A1 (en) * | 2022-12-30 | 2024-07-04 | 越洋医药开发(广州)有限公司 | Controlled release tablet of loxoprofen sodium, preparation method, and use |
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