CN101940561A - Quetiapine fumarate tablet and preparation method thereof - Google Patents
Quetiapine fumarate tablet and preparation method thereof Download PDFInfo
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- CN101940561A CN101940561A CN201010285020XA CN201010285020A CN101940561A CN 101940561 A CN101940561 A CN 101940561A CN 201010285020X A CN201010285020X A CN 201010285020XA CN 201010285020 A CN201010285020 A CN 201010285020A CN 101940561 A CN101940561 A CN 101940561A
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- Prior art keywords
- quetiapine
- acid
- sheet
- gained
- fumarate
- Prior art date
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- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 title claims abstract description 29
- 229960005197 quetiapine fumarate Drugs 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims abstract description 43
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001530 fumaric acid Substances 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 53
- 229960004431 quetiapine Drugs 0.000 claims description 52
- 239000008187 granular material Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 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 17
- 229920002472 Starch Polymers 0.000 claims description 17
- 239000008101 lactose Substances 0.000 claims description 17
- 239000008107 starch Substances 0.000 claims description 17
- 235000019698 starch Nutrition 0.000 claims description 17
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 14
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 14
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 14
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 14
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 14
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 14
- 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 12
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- 229910052708 sodium Inorganic materials 0.000 claims description 12
- 238000004090 dissolution Methods 0.000 claims description 11
- 239000012530 fluid Substances 0.000 claims description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 9
- 239000011976 maleic acid Substances 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- 239000001117 sulphuric acid Substances 0.000 claims description 9
- 235000011149 sulphuric acid Nutrition 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 7
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 6
- 238000000576 coating method Methods 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000000945 filler Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 3
- 238000009501 film coating Methods 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 239000010409 thin film Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 8
- 150000007513 acids Chemical class 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 229920003081 Povidone K 30 Polymers 0.000 description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 150000007524 organic acids Chemical class 0.000 description 8
- 238000000605 extraction Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000009492 tablet coating Methods 0.000 description 5
- 239000002700 tablet coating Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960004170 clozapine Drugs 0.000 description 3
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-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 2
- 229920000881 Modified starch Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000013022 formulation composition Substances 0.000 description 2
- 229960002598 fumaric acid Drugs 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940028937 divalproex sodium Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- -1 fluidizer Substances 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- ZTHJULTYCAQOIJ-WXXKFALUSA-N quetiapine fumarate Chemical compound [H+].[H+].[O-]C(=O)\C=C\C([O-])=O.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 ZTHJULTYCAQOIJ-WXXKFALUSA-N 0.000 description 1
- 229940035004 seroquel Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a quetiapine fumarate tablet which comprises active ingredient quetiapine fumarate or pharmaceutically acceptable salt, and at least one pharmaceutic adjuvant; the quetiapine fumarate tablet also comprises one or more specific acids which can promote a medicine to be rapidly dissolved out; and fumaric acid is preferentially selected. The invention also relates to a preparation method of the quetiapine fumarate tablets. By the invention, the product which can be rapidly dissolved out and has good stability can be acquired, and the quality of the product can be improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to Quetiapine sheet and preparation method thereof.
Background technology
Quetiapine is a kind of atypical antipsychotic agents, and its structure is similar to clozapine, belongs to two Benzodiazepines derivants, has both kept the curative effect characteristics of clozapine, has overcome untoward reaction such as the agranulocytosis that clozapine may cause, obesity, anticholinergic again.Now with
(Seroquel) is the trade name listing, is used for schizoid treatment as monotherapy or as the complementary therapy of lithium agent or divalproex sodium (Divalproex), with the treatment of the acute manic property outbreak relevant with I type amphicheirality obstacle.
US4879288 discloses the synthetic method of Quetiapine, also discloses the Quetiapine sheet among the embodiment, comprises adjuvant lactose commonly used, polyvidone, Sodium ethylate starch, pregelatinized Starch, corn starch, magnesium stearate etc.
CN200710043404 discloses slow (control) release formulation compositions of quetiapine fumarate and application thereof, and wherein compositions comprises quetiapine fumarate, organic acid, water soluble polymer, enteric material, wax class, water-insoluble macromolecule.
CN200810166425 discloses quetiapine fumarate oral cavity disintegration tablet and preparation method thereof, comprises quetiapine fumarate, disintegrating agent, filler, correctives of special ratios etc.
Quetiapine chemical name: 11-{4-[2-(2-(hydroxy ethoxy) ethyl-1-piperazine]) dibenzo [b, f] [1,4] sulfur azatropylidene } 1/2 fumarate, CAS number: 111974-69-7, be dissolved in DMF, be slightly soluble in ethanol, the atomic dichloromethane that is dissolved in, insoluble in the water.Because Quetiapine insoluble character in water makes the qualified big difficult point that becomes the Quetiapine sheet of dissolution.For addressing this problem, in adjuvant, add the more of solubilizing agent in the prior art.For example in the Quetiapine granule of the 500mg specification that Japan goes on the market, just contain the solubilizing agent sodium lauryl sulphate.Though low dose of quetiapine fumarate sheet does not add solubilizing agent, its dissolution velocity is slower, can not reach complete stripping very soon.Quetiapine is the spiritual class medicine of treatment in addition, the patient need take for a long time, and solubilizing agent such as sodium lauryl sulphate have certain zest and toxicity, adds solubilizing agent in quetiapine formulations, the patient takes for a long time and might make health produce infringement, and safety can not get guaranteeing.
Slow (control) release formulation compositions of CN200710043404 protection quetiapine fumarate and application thereof.Wherein point out to add organic acid and can play solubilization, selected organic acid comprises tartaric acid, citric acid, lactic acid, para-amino benzoic acid, P-hydroxybenzoic acid or gentisic acid.Slow (control) release formulation can continue slowly to discharge medicine (or keeping medicine in certain concentration) in a long time to reach the preparation that prolongs the drug effect purpose after meaning medication.The inventor finds through experiment, with respect to not adding the organic acid prescription, adding organic acid described in this piece patent in slow releasing preparation can increase the Quetiapine stripping really slowly in the long time, but we need reach result of extraction faster at the Quetiapine ordinary tablet.Find in the research process that a lot of organic acid comprise that several organic acid of mentioning in the above-mentioned patent all can not make Quetiapine reach quick stripping within 15 minutes.The inventor can make the Quetiapine rapid release through discovering fumaric acid in the organic acid, maleic acid, these three kinds of acid of benzenesulfonic acid continuously, stripping can reach more than 85% within 15 minutes, in addition the inventor also find in the mineral acid sulphuric acid, hydrochloric acid same solubilizing effect also arranged, this discovery has solved insoluble drug Quetiapine slow problem of stripping when the preparation ordinary tablet.
Summary of the invention
The invention provides a kind of new Quetiapine sheet, after in prescription, adding one or more specific acid, can make the rapid stripping of Quetiapine sheet, drug dissolution was at 15 minutes, even just can reach more than 85% in 10 minutes, solved the bad problem of insoluble drug Quetiapine stripping in preparation, improve bioavailability, thereby reached therapeutic effect.
Quetiapine sheet provided by the invention contains active component Quetiapine or its pharmaceutically acceptable salt, and at least a pharmaceutic adjuvant, and special described Quetiapine sheet contains one or more acid that are selected from fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, the hydrochloric acid.
By the Quetiapine more easily dissolving in acidic materials as can be known of existing document, through constantly exploring, the discovery that the inventor is surprised adds one or more made Quetiapines of fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, hydrochloric acid in the Quetiapine sheet dissolution is greatly improved.
Quetiapine sheet of the present invention, wherein active component is a quetiapine fumarate.
Quetiapine sheet among the present invention, the preferred fumaric acid of described acid.
The consumption of the acid described in the present invention accounts for the 3%-10% of total formulation weight amount, and preferably 4%-8% is more preferably 5%.It is too high or too low that the inventor finds that the consumption of acid accounts for the ratio of total formulation weight amount, and the result of extraction of product is all undesirable, and is best at 5% o'clock result of extraction.
The contained pharmaceutic adjuvant of Quetiapine sheet of the present invention comprises one or more of filler, disintegrating agent, binding agent, fluidizer, lubricant.
The optional lactose of filler, microcrystalline Cellulose, starch in the above-mentioned adjuvant; The optional carboxymethyl starch sodium of disintegrating agent, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, polyvinylpolypyrrolidone; The optional polyvidone of binding agent, starch; The optional magnesium stearate of lubricant, sodium stearyl fumarate.
Quetiapine sheet of the present invention, wherein label is made up of the material of following percentage by weight: quetiapine fumarate or its officinal salt 28-45%, fumaric acid 4-8%, lactose 20-50%, microcrystalline Cellulose 10-30%, carboxymethyl starch sodium 2-5%, polyvidone 0-5%, sodium stearyl fumarate 1-3%.
The inventor also finds one or more acid in Quetiapine and fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, the hydrochloric acid are dissolved in the hot water, adds in the preparation after stirring cooling again, and the result of extraction of product is than directly adding better.
Therefore, the present invention also comprises the method for this new Quetiapine sheet of preparation, and this method may further comprise the steps:
(1) Quetiapine or its pharmaceutically acceptable salt are dissolved in the hot water with one or more acid that are selected from fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, the hydrochloric acid;
(2) step (1) gained solution stirring is cooled off;
(3) partial supplementary material is added fluid bed, granulating also with step (2) gained solution, drying obtains dried granule;
(4) the dried granule of step (3) gained and all the other adjuvant mix homogeneously are obtained mixing granule;
(5) step (4) gained is mixed granule and be pressed into tablet;
(6) optional, with step (5) gained tablet stomach dissolution type thin film coating material coating, coating weightening finish 1%-6%.
The method according to this invention preferably may further comprise the steps:
(1) quetiapine fumarate and fumaric acid are dissolved in the hot water;
(2) step (1) gained solution stirring is cooled off;
(3) partial supplementary material is added fluid bed, granulating also with step (2) gained solution, drying obtains dried granule;
(4) the dried granule of step (3) gained and all the other adjuvant mix homogeneously are obtained mixing granule;
(5) step (4) gained is mixed granule and be pressed into tablet;
(6) optional, with step (5) gained tablet stomach dissolution type thin film coating material coating, coating weightening finish 1%-6%.
Above-mentioned hot water is meant that temperature is at 50 ℃-100 ℃ water.
Quetiapine sheet described in the present invention is meant common tablet in addition.
Description of drawings
Accompanying drawing 1: embodiment 1-3 product stripping curve contrast
The specific embodiment
By following specific embodiment, can help the reader better to understand the present invention, but following example can not be construed as limiting the present invention.
Embodiment 1～3
* embodiment 1 only is used to do contrast, does not belong to content of the present invention.
Preparation method:
Embodiment 1: quetiapine fumarate, lactose, microcrystalline Cellulose, carboxymethyl starch sodium, 30 POVIDONE K 30 BP/USP 30 are put into fluid bed mix, add purified water granulation after drying, granulate must be done granule, adds the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet, with tablet coating.
Embodiment 2: quetiapine fumarate, fumaric acid, lactose, microcrystalline Cellulose, carboxymethyl starch sodium, 30 POVIDONE K 30 BP/USP 30 are mixed, add purified water granulation after drying, granulate must be done granule, adds the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet, with tablet coating.
Embodiment 3:(1) quetiapine fumarate and fumaric acid are dissolved in 70 ℃ hot water, put cold, stir 8 hours standby.(2) lactose, microcrystalline Cellulose, 30 POVIDONE K 30 BP/USP 30, carboxymethyl starch sodium are added in the fluid bed and granulate, must do granule after the drying, granulate with step (1) gained Quetiapine solution, in dried granule, add the sodium stearyl fumarate mix homogeneously, tabletting gets tablet, with tablet coating.
Embodiment 1-3 gained coated tablet is pressed 2010 editions appendix XC of Chinese Pharmacopoeia dissolution method, second method, is dissolution medium with the 900ml purified water, and rotating speed of agitator 50rpm measures stripping curve, the results are shown in accompanying drawing 1.
Comparative test result shows: product does not add specific acid among the comparative example 1, dissolution had only 50% in 10 minutes, and embodiments of the invention 2 and 3 add specific acid in tablet after, dissolution reached 80% and 88% respectively in 10 minutes, and the dissolution of Quetiapine obtains very significantly improving with respect to embodiment 1.The result of extraction that also can find out embodiment 3 makes progress again than embodiment 2.Explanation after the dissolving is granulated Quetiapine in hot water with acid again can further accelerate dissolution rate.
Embodiment 4
| Material | Consumption (mg/ sheet) | Ratio |
| Quetiapine fumarate | 28.8 | 28.80％ |
| Fumaric acid | 5.0 | 5.00％ |
| Lactose | 44.2 | 44.20％ |
| Microcrystalline Cellulose | 15.0 | 15.00％ |
| Carboxymethyl starch sodium | 3.0 | 3.00％ |
| 30 POVIDONE |
1.0 | 1.00％ |
| Sodium stearyl fumarate | 3.0 | 3.00％ |
| Amount to | 100 | 100.00％ |
Preparation method:
(1) quetiapine fumarate, fumaric acid and 30 POVIDONE K 30 BP/USP 30 are dissolved in 50 ℃ hot water, put coldly, stirred 8 hours.
(2) lactose, microcrystalline Cellulose, carboxymethyl starch sodium are granulated, must be done granule behind dry, the granulate with step (1) gained Quetiapine solution in fluid bed, add the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet, with tablet coating.
Embodiment 5
| Material | Consumption (mg/ sheet) | Ratio |
| Quetiapine fumarate | 345.8 | 45.24％ |
| Fumaric acid | 59.7 | 7.81％ |
| Lactose | 211.1 | 27.62％ |
| Microcrystalline Cellulose | 84.2 | 11.02％ |
| Carboxymethyl starch sodium | 32.9 | 4.30％ |
| 30 POVIDONE |
7.7 | 1.01％ |
| Sodium stearyl fumarate | 22.9 | 3.00％ |
| Amount to | 764.3 | 100.00％ |
Preparation method:
(1) quetiapine fumarate, fumaric acid and 30 POVIDONE K 30 BP/USP 30 are dissolved in 50 ℃ hot water, put coldly, stirred 8 hours.
(2) lactose, microcrystalline Cellulose, carboxymethyl starch sodium are used in fluid bed step gained Quetiapine solution is granulated, must be done granule behind dry, the granulate, add the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet, with tablet coating.
Embodiment 6
| Prescription | Consumption (mg/ sheet) | Ratio |
| Quetiapine fumarate | 153.0 | 30.00％ |
| Maleic acid | 20.4 | 4.00％ |
| Lactose | 179.52 | 35.20％ |
| Starch | 127.5 | 25.00％ |
| Polyvinylpolypyrrolidone | 10.2 | 2.00％ |
| 30 POVIDONE |
9.18 | 1.80％ |
| Magnesium stearate | 10.2 | 2.00％ |
| Amount to | 510 | 100.00％ |
Preparation method:
(1) quetiapine fumarate and maleic acid are dissolved in 60 ℃ hot water, put coldly, stirred 8 hours.
(2) lactose, starch, 30 POVIDONE K 30 BP/USP 30, polyvinylpolypyrrolidone are mixed, in fluid bed, granulate, must do granule behind dry, the granulate with step (1) gained Quetiapine solution, adding magnesium stearate mix homogeneously in dried granule, tabletting gets tablet.
Embodiment 7
| Prescription | Consumption (mg/ sheet) | Ratio |
| Quetiapine fumarate | 204 | 40.00％ |
| Sulphuric acid | 15.3 | 3.00％ |
| Lactose | 102 | 20.00％ |
| Microcrystalline Cellulose | 135.15 | 26.50％ |
| Cross-linking sodium carboxymethyl cellulose | 25.5 | 5.00％ |
| 30 |
15.3 | 3.00％ |
| Sodium stearyl fumarate | 12.75 | 2.50％ |
| Amount to | 510 | 100.00％ |
Preparation method:
(1) quetiapine fumarate and sulphuric acid are dissolved in 100 ℃ hot water, put coldly, stirred 8 hours.
(2) lactose, microcrystalline Cellulose, 30 POVIDONE K 30 BP/USP 30, cross-linking sodium carboxymethyl cellulose are added in the fluid bed and granulate, must do granule after the drying, granulate with step (1) gained Quetiapine solution, add the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet.
Embodiment 8
| Prescription | Consumption (mg/ sheet) | Ratio |
| Quetiapine fumarate | 214.2 | 42.00％ |
| Hydrochloric acid | 17.85 | 3.50％ |
| Fumaric acid | 17.85 | 3.50％ |
| Lactose | 145.35 | 28.50％ |
| Microcrystalline Cellulose | 78.03 | 15.30％ |
| Carboxymethyl starch sodium | 25.5 | 5.00％ |
| 30 |
5.1 | 1.00％ |
| Sodium stearyl fumarate | 6.12 | 1.20％ |
| Amount to | 510 | 100.00％ |
Preparation method:
(1) hydrochloric acid, fumaric acid and quetiapine fumarate are dissolved in 70 ℃ hot water, put coldly, stirred 8 hours.
(2) lactose, microcrystalline Cellulose, 30 POVIDONE K 30 BP/USP 30, carboxymethyl starch sodium are added in the fluid bed and granulate, must do granule after the drying, granulate with step (1) gained Quetiapine solution, add the sodium stearyl fumarate mix homogeneously in dried granule, tabletting gets tablet.
Claims (9)
1. a Quetiapine sheet contains active component Quetiapine or its pharmaceutically acceptable salt, and at least a pharmaceutic adjuvant, it is characterized in that described Quetiapine sheet contains one or more acid that are selected from fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, the hydrochloric acid.
2. Quetiapine sheet as claimed in claim 1 is characterized in that active component is a quetiapine fumarate.
3. Quetiapine sheet as claimed in claim 1 is characterized in that described acid is selected from fumaric acid.
4. Quetiapine sheet as claimed in claim 1 is characterized in that the consumption of described acid accounts for the 3%-10% of total formulation weight amount.
5. Quetiapine sheet as claimed in claim 1 is characterized in that the consumption of described acid accounts for the 4%-8% of total formulation weight amount.
6. Quetiapine sheet as claimed in claim 1 is characterized in that pharmaceutic adjuvant wherein comprises one or more of filler, disintegrating agent, binding agent, lubricant.
7. as arbitrary described Quetiapine sheet of claim 1-6, it is characterized in that label wherein comprises the material of following percentage by weight: quetiapine fumarate or its officinal salt 28-46%, fumaric acid 4-8%, lactose 20-50%, microcrystalline Cellulose 10-30%, carboxymethyl starch sodium 2-5%, polyvidone 0-5%, sodium stearyl fumarate 1-3%.
8. method for preparing Quetiapine sheet as claimed in claim 1 is characterized in that this method may further comprise the steps:
(1) Quetiapine or its pharmaceutically acceptable salt are dissolved in the hot water with one or more acid that are selected from fumaric acid, maleic acid, benzenesulfonic acid, sulphuric acid, the hydrochloric acid;
(2) step (1) gained solution stirring is cooled off;
(3) partial supplementary material is added fluid bed, granulating also with step (2) gained solution, drying obtains dried granule;
(4) the dried granule of step (3) gained and all the other adjuvant mix homogeneously are obtained mixing granule;
(5) step (4) gained is mixed granule and be pressed into tablet;
(6) optional, with step (5) gained tablet stomach dissolution type thin film coating material coating, coating weightening finish 1%-6%.
9. the preparation method of Quetiapine sheet as claimed in claim 8, wherein said hot water refer to that temperature is 50 ℃-100 ℃ a water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010285020XA CN101940561A (en) | 2010-09-14 | 2010-09-14 | Quetiapine fumarate tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010285020XA CN101940561A (en) | 2010-09-14 | 2010-09-14 | Quetiapine fumarate tablet and preparation method thereof |
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| Publication Number | Publication Date |
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| CN102206195A (en) * | 2011-03-25 | 2011-10-05 | 浙江华海药业股份有限公司 | Crystalline quetiapine fumarate and pharmaceutical compositions thereof |
| CN102406606A (en) * | 2011-11-29 | 2012-04-11 | 海南美大制药有限公司 | Quetiapine fumarate liposome solid preparation |
| CN102614140A (en) * | 2011-01-26 | 2012-08-01 | 浙江九洲药物科技有限公司 | Iloperidone oral disintegrating tablet and its preparation method |
| CN104644644A (en) * | 2015-01-27 | 2015-05-27 | 美吉斯制药（厦门）有限公司 | Quetiapine fumarate pharmaceutical composition |
| CN107582534A (en) * | 2017-09-27 | 2018-01-16 | 南京正科医药股份有限公司 | A kind of quetiapine fumarate piece and preparation method thereof |
| CN112516101A (en) * | 2020-11-19 | 2021-03-19 | 南京海纳医药科技股份有限公司 | Tablet containing quetiapine fumarate and preparation method thereof |
| CN114814045A (en) * | 2022-06-27 | 2022-07-29 | 湖南慧泽生物医药科技有限公司 | Method for determining in-vitro release degree of quetiapine fumarate sustained release tablets |
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| CN107582534A (en) * | 2017-09-27 | 2018-01-16 | 南京正科医药股份有限公司 | A kind of quetiapine fumarate piece and preparation method thereof |
| CN112516101A (en) * | 2020-11-19 | 2021-03-19 | 南京海纳医药科技股份有限公司 | Tablet containing quetiapine fumarate and preparation method thereof |
| CN114814045A (en) * | 2022-06-27 | 2022-07-29 | 湖南慧泽生物医药科技有限公司 | Method for determining in-vitro release degree of quetiapine fumarate sustained release tablets |
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