CN102688209A - Lurasidone tablet and preparation method thereof - Google Patents
Lurasidone tablet and preparation method thereof Download PDFInfo
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- CN102688209A CN102688209A CN2012102068442A CN201210206844A CN102688209A CN 102688209 A CN102688209 A CN 102688209A CN 2012102068442 A CN2012102068442 A CN 2012102068442A CN 201210206844 A CN201210206844 A CN 201210206844A CN 102688209 A CN102688209 A CN 102688209A
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- tablet
- laxi ketone
- laxi
- ketone
- sugar alcohol
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- 238000002360 preparation method Methods 0.000 title abstract description 34
- PQXKDMSYBGKCJA-CVTJIBDQSA-N lurasidone Chemical compound C1=CC=C2C(N3CCN(CC3)C[C@@H]3CCCC[C@H]3CN3C(=O)[C@@H]4[C@H]5CC[C@H](C5)[C@@H]4C3=O)=NSC2=C1 PQXKDMSYBGKCJA-CVTJIBDQSA-N 0.000 title abstract description 8
- 229960001432 lurasidone Drugs 0.000 title abstract description 7
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 19
- 239000001913 cellulose Substances 0.000 claims abstract 2
- 229920002678 cellulose Polymers 0.000 claims abstract 2
- 150000002576 ketones Chemical class 0.000 claims description 66
- 239000011248 coating agent Substances 0.000 claims description 20
- 238000000576 coating method Methods 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000011230 binding agent Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 13
- 239000000314 lubricant Substances 0.000 claims description 13
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 11
- -1 liquid Paraffin Substances 0.000 claims description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 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 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 239000000080 wetting agent Substances 0.000 claims description 7
- 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 6
- 229920000881 Modified starch Polymers 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 235000021355 Stearic acid Nutrition 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 5
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- 239000008117 stearic acid Substances 0.000 claims description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- 239000011812 mixed powder Substances 0.000 claims description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 4
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- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 3
- 239000004368 Modified starch Substances 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 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 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 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 3
- 229940057995 liquid paraffin Drugs 0.000 claims description 3
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- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
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- 239000000600 sorbitol Substances 0.000 claims description 3
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
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- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 15
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 238000010298 pulverizing process Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
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- 238000007689 inspection Methods 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
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- 229960001855 mannitol Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- TURGQPDWYFJEDY-UHFFFAOYSA-N 1-hydroperoxypropane Chemical class CCCOO TURGQPDWYFJEDY-UHFFFAOYSA-N 0.000 description 1
- QUTGXAIWZAMYEM-UHFFFAOYSA-N 2-cyclopentyloxyethanamine Chemical compound NCCOC1CCCC1 QUTGXAIWZAMYEM-UHFFFAOYSA-N 0.000 description 1
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 1
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- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
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- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
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- 229940036674 latuda Drugs 0.000 description 1
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
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- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a lurasidone tablet and a preparation method thereof. The lurasidone tablet comprises lurasidone shown in the formula (I), cellulose derivative and sugar alcohol. The prepared lurasidone preparation, especially lurasidone tablet, has good release performance and excellent mechanical performance.
Description
Technical field
The present invention relates to the solid composite medicament of Lu Laxi ketone, particularly relate to Lu Laxi ketone sheet and method for preparing.
Background technology
Hydrochloric acid Lu Laxi ketone (Lurasidone HCl; In the present invention; The hydrochlorate of this material can be described as Lu Laxi ketone) be a novel atypical antipsychotic agents; U.S. food and medicine Surveillance Authority on October 28,2010 (FDA) ratify its listing, commodity are called Latuda, are used to treat schizophrenia.It is antipsychotic agent with dual function by the exploitation of SUMITOMO CHEMICAL drugmaker.It all has high affinity to 5-HT2A receptor and d2 dopamine receptor.The insane positive and negative symptoms are all had significant curative effect, have research report Lu Laxi ketone can improve cognitive function.The recommendation initial dose is 40mg/d, and effective dosage ranges is 40～120mg/d, and maximum recommended dosage is 80mg/d; Lu Laxi ketone should be taken with food simultaneously.The less weight increase that causes of Lu Laxi ketone does not cause that glucose, lipid (lipoid), ECG and QT interval change.
The chemistry of Lu Laxi ketone by name (3aR, 4S, 7R, 7aS)-2-{ (1R, 2R)-[4-(1 for 2-; 2-benzisothiazole-3-yl) piperazine-1 ylmethyl] cyclohexyl methyl } six hydrogen-4,7-methylene-2H-iso-indoles-1,3-dione hydrochloride, English chemistry (3aR, 4S by name; 7R, 7aS)-2-{ (1R, 2R)-2-[4-(1,2-benzisothiazol-3-yl) piperazin-1ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1; 3-dione hydrochloride also has document to be called: N-[4-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl]-(2R, 3R)-2,3-tetramethylene-butyl]-(1 ' R; 2 ' S, 3 ' R, 4 ' S)-2,3-bicyclo-[2; 2,1] heptane imidodicarbonic diamide hydrochlorate, molecular formula are C28H36N4O2SHCl, and molecular weight is 529.14; Its chemical structural formula is:
Lu Laxi ketone tablet applications is arranged at present clinically in the patient., persistence short with quick-acting, onset time in order to bring into play is the drug effect of the desired Lu Laxi ketone of characteristic, and the said preparation expectation has rapid release property.But, because Lu Laxi ketone is insoluble drug, under many prescription preparation conditions, can't obtain sufficient rapid release property, thereby the report (CN101184489A) of processing the preparation that makes it to contain pregelatinized Starch is arranged.In addition, the tablet of expectation Lu Laxi ketone is a kind of coated preparation, yet the mechanical damage of coated preparation in the coating operation should be considered especially.Thereby the preparation that people expect Lu Laxi ketone particularly tablet not only has good release performance, but also expectation has the favorable mechanical performance.
Summary of the invention
The preparation that the object of the present invention is to provide a kind of Lu Laxi ketone is tablet particularly, and this preparation expectation has good pharmaceutical property.The present invention has realized the pharmaceutical property of one or more expectations through the tablet of the Lu Laxi ketone that following scheme provided.
[1], a kind of Lu Laxi ketone tablet, it comprises: Lu Laxi ketone, low-substituted hydroxypropyl cellulose and sugar alcohol shown in the formula (I),
[2], according to the Lu Laxi ketone tablet of project [1], wherein said Lu Laxi ketone accounts for the 10-50% (for example 15-45%, for example 20-45%) of tablet weight.
[3], according to the Lu Laxi ketone tablet of project [1-2], wherein said low-substituted hydroxypropyl cellulose accounts for the 15-50% (for example 20-50%, for example 20-45%) of tablet weight.
[4], according to the Lu Laxi ketone tablet of project [1-3], wherein said sugar alcohol accounts for the 5-50% (for example 10-50%, for example 10-45%) of tablet weight.
[5], according to the Lu Laxi ketone tablet of project [1-4], wherein said sugar alcohol is to be selected from following one or more: mannitol, lactose, sorbitol, sucrose, fructose, preferred sugar alcohol is to be selected from following one or more mannitol, lactose.
[6], according to the Lu Laxi ketone tablet of project [1-5], wherein can also comprise one or more and be selected from following filler: starch, dextrin, microcrystalline Cellulose, modified starch.Exemplarily, this filler can account for the 5-50% (for example 10-45%, for example 10-40%, for example 10-30%) of tablet weight, and in a preferred version, this filler is a microcrystalline Cellulose.
[7], according to the Lu Laxi ketone tablet of project [1-6], wherein can also comprise one or more and be selected from following adjuvant: binding agent, lubricant, fluidizer, its amount account for the 1-20% (for example 2-15%, for example 1-10%, for example 1-5%) of tablet weight.Described binding agent for example can be water-soluble polymer (being mixed with hydroxypropyl emthylcellulose, polyvinylpyrrolidone, polyvinyl alcohol of aqueous solution etc. when for example preparing tablet).Said lubricant is magnesium stearate, stearic acid, zinc stearate, liquid Paraffin, Polyethylene Glycol, hydrogenated vegetable oil or its combination for example.Said fluidizer is silicon dioxide, silica sol, micropowder silica gel, Pulvis Talci etc. or its combination for example.
[8], according to the Lu Laxi ketone tablet of project [1-7], wherein the mean diameter of Lu Laxi ketone is 0.1-8um, for example 0.1-5um.
[9], according to the Lu Laxi ketone tablet of project [1-8], it is the tablet of coating.
[10], according to the Lu Laxi ketone tablet of project [1-9], wherein the amount of Lu Laxi ketone is 10 ~ 160mg in each tablet, 20 ~ 120mg for example, for example about 20mg, for example about 40mg, for example about 60mg, for example about 80mg, for example about 100mg, for example about 120mg.
[11], the method for the Lu Laxi ketone tablet of preparation project [1-10], it comprises the steps: Lu Laxi ketone, sugar alcohol and part or all low-substituted hydroxypropyl cellulose, mix homogeneously; Water or aquiferous ethanol for example concentration are lower than the ethanol (as wetting agent) of 40% (for example being lower than 20%) or with binder aqueous solution this mixed powder are carried out wet granulation, drying; The low-substituted hydroxypropyl cellulose (if existence) that adds surplus, and optional lubricant, fluidizer, mix homogeneously; Tabletting; Randomly carry out coating.
[12], the method for the Lu Laxi ketone tablet of preparation project [1-11], it comprises the steps: Lu Laxi ketone, sugar alcohol and part or all low-substituted hydroxypropyl cellulose, and optional filler mix homogeneously, obtains mixed powder; Water (as wetting agent) perhaps carries out wet granulation, drying with binder aqueous solution to this mixed powder again; The low-substituted hydroxypropyl cellulose (if existence) that adds surplus, and optional lubricant, fluidizer, mix homogeneously; Tabletting; Randomly carry out coating.
The specific embodiment
Lu Laxi ketone is known to have antipsychotic effect, and it can be used as the medicine to schizophrenia etc.Described chemical compound is joined in the said preparation, for example adds with 10 to 50wt% of tablet (plain sheet) gross weight, preferably with 15 to 45wt%, particularly with 20 to 40wt%.In addition, preferably with the fine grinding of this chemical compound, for example 90% volume or more particle have 27um or small particle diameter, for example comprise that in the mean diameter (that is, 50% particle volume diameter) of volume ratio 0.1 to 8um, and preferred 1 to 4um.The content of every middle Lu Laxi ketone is 10-160mg, is preferably 20 to 120mg, more elects 40 as to 120mg.
" low-substituted hydroxypropyl cellulose " according to the invention can be abbreviated as L-HPC, refers to cellulosic low substituted hydroxy-propyl ether, and it is at dry 1 hour of 105 ° of C, its hydroxypropyl (-OCH
2CHOHCH
3) content should be 5% ~ 16%.The used low-substituted hydroxypropyl cellulose of the present invention can be its extensive stock form.It is in the present invention usually with the for example 15-50% of tablet (plain sheet) gross weight, 20-50% for example, and for example the amount of 20-45% adds.
In the present invention, said " sugar alcohol " comprises for example mannitol, lactose, sucrose, sorbitol, D-sorbitol, erythritol, xylitol, fructose etc.Preferred mannitol and the lactose of comprising.Equally, said sugar alcohol can use separately, or two kinds or more kinds ofly unite use.Said amount of sugar alcohol for example is the 5-50% (for example 10-45%, for example 10-40%) of tablet (plain sheet) weight.The mean diameter of mannitol and lactose mannitol for example is 10 to 200um.
In the tablet, can also comprise that one or more are selected from following filler: starch is corn starch, dextrin, microcrystalline Cellulose, modified starch for example in the present invention.These filleies can use separately, or two or more unite use.Find in special instance of the present invention to use microcrystalline Cellulose to have excellent especially effect as filler.
In the present invention, as the binding agent of " water-soluble polymer ", it for example comprises, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, or the like.The hydroxypropyl cellulose that comprises that choosing is more arranged, hydroxypropyl emthylcellulose, polyvinylpyrrolidone or polyvinyl alcohol.Said water-soluble copolymer adhesive can use separately, also can two or more unite use.Said water-soluble copolymer adhesive combined amount for example be the tablet total weight amount 0.5 to 10wt%, preferred 1 to 5wt%.The oral formulations of employing pharmaceutical compositions of the present invention is meant and is mixed with tablet, capsule, granule or fine grain pharmaceutical preparation.Said preparation can the application of the invention prescription etc. be processed tablet, capsule, granule or fine grained through traditional method.
In the present invention; When the amount of calculating certain component accounts for the percent of tablet weight of the present invention; Under situation about not explaining in addition; It calculates the i.e. tablet meter of coating not of the normally plain sheet in basis, and for example phrase " Lu Laxi ketone accounts for the 10-50% of tablet weight " is illustrated in that Lu Laxi ketone accounts for this not 10-50% of the plain sheet weight of coating in the plain sheet.Yet it will be apparent to those skilled in the art that; Even with tablet coating of the present invention, owing to the sheet of coating weightening finish for whole tablet heavily changes not quite, therefore above-mentioned metering method and metering ratio also go for coated tablet; Promptly; For example, phrase " Lu Laxi ketone accounts for the 10-50% of tablet weight " be illustrated in tablet of the present invention coated after, Lu Laxi ketone accounts for the 10-50% of this coated tablet weight in the coated tablet.
In addition, in the present invention, only if special linguistic context is arranged, otherwise % representes the percent of w/w.
In the present invention, lubricant and fluidizer can rise and be referred to as lubricant.Lubricant includes but not limited to: magnesium stearate, stearic acid, zinc stearate, liquid Paraffin, Polyethylene Glycol, silicon dioxide, silica sol, micropowder silica gel, Pulvis Talci, hydrogenated vegetable wet goods or its combination.
Tablet of the present invention can adopt traditional method to prepare according to required dosage form:
(1) when binding agent exists, the aqueous solution of preparation water-soluble copolymer adhesive: water-soluble copolymer adhesive is dissolved in the pure water.The amount of water-soluble copolymer adhesive for example be pure water weight 1 to 20wt%, preferred 2 to 8wt%; When without binding agent, be the granulation that wetting agent is used for the back with water.
(2) preparation contains the granule of Lu Laxi ketone: in fluidised bed granulator or stirring granulating machine, add and contain Lu Laxi ketone, sugar alcohol, all or part of low-substituted hydroxypropyl cellulose; With optional excipient such as filler, the water-soluble copolymer adhesive or the water that on it, are sprayed at step (1) preparation are granulated.The equipment that is used to granulate for example comprises: the equipment of fluidized bed granulation, high-speed cutting granulation, rotation fluidized bed granulation etc., but be not limited to these.
(3) dried particles: the above-mentioned granule that obtains is dry under decompression or atmospheric pressure.Exsiccant standard be the loss on drying that records through infrared moisture meter for example in the 3wt%, be preferably 1-2wt%.
(4) hybrid lubricant: the low-substituted hydroxypropyl cellulose to add optional lubricant and (if existence) surplus in above-mentioned (3) dried granules, mix.In order to reach purpose of mixing, can use the blender that for example belongs to diffusion mixer type [cylinder].Especially, use cylinder type blender, V blender, bicone blender, hopper type blender, or the like, but be not limited to these.
(5) tabletting: the said mixture tabletting is obtained tablet.
The equipment that is used for tabletting comprises the equipment that for example belongs to the tablet machine type, or the like.Select tabletting hardness, for example scope is 30 to 200N.
(6) optionally carry out film coating: if desired, the above-mentioned tablet that obtains can be chosen wantonly through film coating.The equipment that is used for coating comprises the equipment that for example belongs to the coating pan type.Be preferably and comprise the equipment that belongs to perforation coating system.
Coating reagent for example comprises; Matrix material mixture (like hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol or the like) and plasticizer are (like Polyethylene Glycol, propylene glycol, glyceryl triacetate; Triethyl citrate, glycerol, fatty acid glyceride; Polyethylene Glycol, or the like).If desired, can be to the additive that wherein adds such as titanium oxide.Behind film coating, also can add Brazil wax etc. as polishing agent.(7) drying: the above-mentioned tablet that obtains is dry.Dry carry out under decompression or the atmospheric pressure so that through loss on drying that infrared moisture meter records for example in the 3wt%, be preferably 1-2wt%.
Embodiments of the invention are described below.Said embodiment is used for exemplary illustration the present invention rather than limits the invention.
A, preparation comprise the conventional method of the tablet of Lu Laxi ketone:
Among below each embodiment and Comparative Examples, use the method for following steps to prepare tablet.
(1) preparation wetting agent or binder solution: water intaking or concentration are lower than the ethanol of 40% (for example be lower than 30%, for example be lower than 20%) as wetting agent; Perhaps with pure water as the solvent preparation hereinafter said binder solution of filling a prescription.
(2) granulate: Lu Laxi ketone (being crushed to particle diameter 0.1-5um in advance), sugar alcohol (pulverizing and cross 100 mesh sieves), part or all of L-HPC (are pulverized and also cross 100 mesh sieves; Adding part in the wet granular) in the fluidised bed granulator of packing into, wetting agent through under following condition, being utilized in above-mentioned (1) preparation or binder solution are processed granule through spray granulation with mixture and are obtained particle powder.In the particle powder of gained, add surplus L-HPC (if having dried granule Extra Section) and lubricant, mix the tabletting granule that obtains being used for.Wherein granulation condition is: the air supply temperature: 60 ℃, and air-flow: 50 to 65 cubic metres/hour, spray velocity: 13g/ minute, nozzle diameter: 1.2mm, atomisation pressure: 0.12MPa, spray gun position: centre position.In the instance, if not explanation in addition, all the L-HPC of formula ratio and Lu Laxi ketone and sugar alcohol are mixed together below; If under partial L-HPC and Lu Laxi ketone and the blended situation of sugar alcohol, promptly exist under the situation of dried granule Extra Section, with the ratio of " inside/outside ratio " dated two parts L-HPC, but institute is this two-part total amount to L-HPC in the prescription.
(3) tabletting: the granule that is used for tabletting in above-mentioned (2) preparation obtains tablet through rotary tablet machine.According to different formulations sheet reselection procedure punch die specification, make sheet directly be 6-14mm, thickness is 2-6mm, and when tabletting, suitably regulates pressure.In the following example that respectively prepares tablet, like explanation in addition, tablet is all suppressed with the tablet machine of same model; And various tablets all are controlled at the hardness of tablet the scope interior (using the tablet hardness tester of same model to measure tablet hardness) of 5-6kgf (promptly 49 ~ 59 Ns) when compacting.In the instance of following each sample preparation, like not explanation in addition, every batch of preparation is 5000 in batches.As not explanation in addition, the plain sheet of this step gained is used for the test of hereinafter correlated performance, the for example friability of tablet inspection, the test of tablet dissolution etc.
(4) coating randomly: will put into coating pan at the uncoated tablets (plain sheet) of above-mentioned (3) preparation; Preheating 30min, rotating speed are 25-40rpm, and the sheet bed tempertaure is controlled at 35-45 ℃; With the Opadry film coating liquid that has prepared; Spray coating, the coating weightening finish is 1.5-3.0%, checks, packs, gets finished product.
B, preparation tablets example
Embodiment 1-5: prepare tablet of the present invention
Prescription (mg/ sheet)
| Component | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Lu Laxi ketone | ?20 | 40 | ?80 | ?120 | ?90 |
| L-HPC | ?45 | 70 (inside/outside is than 3:1) | ?90 | ?80 | ?80 |
| Lactose | ?33 | 40 | ?100 | ?20 | |
| Mannitol | 40 | ?115 | ?80 | ||
| HPMC* | 5 | ?7.5 | ?10 | ?5 | |
| Water | In right amount | ||||
| Magnesium stearate | ?2 | ?7.5 | ?10 | ?5 | |
| Stearic acid | 5 | ||||
| Amount to | ?100mg | 200mg | ?300mg | ?400mg | ?200mg |
Annotate: * HPMC is mixed with 5% aqueous solution use; Finally the amount of counting is converted to the exsiccant amount of binding agent for measuring shown in each Example formulations, for example among the embodiment 25 be to use shown in binding agent, total addition is HPMC dry product 5mg; When hereinafter has similar situation, also has similar meaning.The 10mg magnesium stearate that embodiment 4 shows is to be made up of 8mg magnesium stearate and 2mg silica sol.
Comparative Examples 1-7: the tablet of preparation Lu Laxi ketone
Respectively with reference to above embodiment 1-5; But respectively L-HPC is wherein replaced with part pre-gelatinized starch (trade name PCS), for example in Comparative Examples 1, it is except replacing with L-HPC the part pre-gelatinized starch; Prescription is identical with embodiment 1 with method for making, prepares the plain sheet of Comparative Examples 1-5.Comparative Examples 6 and 7 is respectively according to lot number 034-15-20 and the method for 034-15-80 and the plain sheet (not coated) that formulation obtains in < test 13>among the CN101184489A; But the tabletting condition is put down in writing referring to preceding text of the present invention " A, preparation comprise the conventional method of tablet of Lu Laxi ketone ", make tablet hardness be controlled at tablet class of the present invention seemingly.
Comparative Examples 8-10: the tablet of preparation Lu Laxi ketone
The above enforcement 4 of reference respectively, but respectively L-HPC consumption wherein is replaced by 60mg (15%), 40mg (10%), 20mg (5%), and the mannitol consumption increases 20mg, 40mg, 60mg respectively.Same method for preparing obtains Comparative Examples 8-10 respectively.
Embodiment 6-10: prepare tablet of the present invention
Prescription (mg/ sheet)
| Component | Embodiment 6 | Embodiment 7 | Embodiment 8 | Embodiment 9 | Embodiment 10 |
| Lu Laxi ketone | ?20 | 40 | ?80 | ?120 | 90 |
| L-HPC | ?45 | 70 (inside/outside is than 3:1) | ?90 | ?80 | 60 |
| Lactose | ?25 | 25 | ?40 | 20 | |
| Mannitol | 25 | ?55 | ?20 | ||
| Microcrystalline Cellulose | ?10 | 30 | ?60 | ?120 | 20 |
| PVP?K30* | 5 | ?7.5 | ?10 | 5 | |
| 20% ethanol | In right amount | ||||
| Magnesium stearate | ?7.5 | ?10 | 5 | ||
| Stearic acid | 5 | ||||
| Amount to | ?100mg | 200mg | ?300mg | ?400mg | 200mg |
* PVP K30 is mixed with 5% aqueous solution use.
Test 1, tablet determination of dissolution rate method
With embodiment in preceding text " B, the preparation tablets example " part and the tablet (all getting the plain sheet that does not pass through coating) that Comparative Examples prepares, pack in the double-layer aluminum-foil bag and (keep away wet), 50 ° of C held 45 days, the sampling and measuring dissolution.Other gets the tablet without the embodiment of above-mentioned high humidity disposal and Comparative Examples preparation, measures dissolution.
According to dissolution method (two appendix XC of Pharmacopoeia of People's Republic of China version in 2010 oar method), use the McilvaineShi buffer solution 900ml of pH4.0 to be dissolution medium, rotating speed is that per minute 50 changes; Operation in accordance with the law, in the time of 30 minutes, it is an amount of to get solution; Filter; It is an amount of that precision is measured subsequent filtrate, quantitatively dilute with dissolution medium, with following HPLC condition test:
Chromatographic column: YMC-Pack AM-312 (5 μ m,
YMC manufactured);
Detector: UV-detector, detect wavelength 230nm;
Column temperature: 25 ° of C
Mobile phase: with following A liquid and B liquid mixing carrying out gradient elution
A liquid: 0.025% trifluoroacetic acid aqueous solution/acetonitrile mixed solution (4:1)
B liquid: 0.025% trifluoroacetic acid acetonitrile solution
Gradient condition
| Time (min) | 0.0 | 60 | 60.1 | 75.0 |
| A liquid (%) | 90.0 | 40.0 | 90.0 | 90.0 |
| B liquid (%) | 10.0 | 60.0 | 10.0 | 10.0 |
Flow velocity: 1ml/min.
Mensuration is without the sample of high-temperature treatment with through the sample of the high-temperature treatment dissolution during at 30 minutes; And the stripping of calculating the dissolution of each lot sample article behind high-temperature treatment dissolution during without high-temperature treatment with respect to this sample changes (%), i.e. stripping changes (%)=(this sample of dissolution ÷ of high-temperature treatment sample is without the dissolution of high-temperature treatment) * 100%.
Each sample sees the following form with its stripping variation (%) without the dissolution of high-temperature treatment:
In addition; The inventor also finds; Though comparing with embodiment 1-5 respectively, each sample of embodiment of the invention 6-10 just used microcrystalline Cellulose basically more; For example embodiment 6 has used microcrystalline Cellulose corresponding to embodiment more than 1, and for example embodiment 10 has used microcrystalline Cellulose corresponding to embodiment more than 5.Yet these embodiment are when carrying out looking into (two appendix XA of Chinese Pharmacopoeia version in 2010) disintegration; The disintegration time of these examples is disintegrate in 4-10 minute all; Yet do not compare with adding microcrystalline Cellulose accordingly, the disintegration time of sample that has added microcrystalline Cellulose is all fast more than 2 minutes.
The friability inspection of test 2, tablet
With the tablet (all getting the plain sheet that does not pass through coating) of embodiment and Comparative Examples preparation in preceding text " B, the preparation tablets example " part, check their friability.Method according under " tablet friability inspection technique " item among two appendix XG of Pharmacopoeia of the People's Republic of China version in 2010 is carried out, and calculate to subtract weight loss (%), and whether the observation tablet has abnormal conditions such as fracture, be full of cracks and/or pulverizing.
The inventor finds, each sample of embodiment 1-10 subtracts weight loss (%) all between 0.1% ~ 0.70%, do not see fracture is arranged, abnormal conditions such as be full of cracks and/or pulverizing; For example each sample of embodiment 1,3,4,6,8 subtracts weight loss (%) all between 0.2% ~ 0.55%.Each sample of Comparative Examples 1 ~ 5,6 ~ 7,8 ~ 10 subtracts weight loss (%) all between 0.95% ~ 1.6%, and some sample has abnormal conditions such as fracture, be full of cracks and/or pulverizing.For example each sample of Comparative Examples 1,2,3,5 subtracts weight loss (%) all between 1.15% ~ 1.6%, and each sample of Comparative Examples 2,5 has abnormal conditions such as fracture, be full of cracks and/or pulverizing; Each sample of Comparative Examples 4,6,7 subtracts weight loss (%) all between 0.95% ~ 1.35%; Each sample of Comparative Examples 8,9,10 subtracts weight loss (%) all between 1.05% ~ 1.25%.Generally speaking, for the tablet of the further coating of needs, through the friability inspection, subtracting weight loss (%) is necessary less than 1%, preferably subtracts weight loss (%) less than 0.9%.And subtract weight loss (%) greater than 0.9% plain sheet, be disadvantageous for avoiding the mechanical damage in the coating worker technology of back.
Claims (10)
1. Yi Zhong Lu Laxi ketone tablet, it comprises: Lu Laxi ketone, cellulose derivative and sugar alcohol shown in the formula (I),
2. according to the Lu Laxi ketone tablet of claim 1, wherein said Lu Laxi ketone accounts for the 10-50% of tablet weight.
3. according to the Lu Laxi ketone tablet of claim 1-2, wherein said low-substituted hydroxypropyl cellulose accounts for the 15-50% of tablet weight.
4. according to the Lu Laxi ketone tablet of claim 1-3, wherein said sugar alcohol accounts for the 5-50% of tablet weight.
5. according to the Lu Laxi ketone tablet of claim 1-4, wherein said sugar alcohol is to be selected from following one or more: mannitol, lactose, sorbitol, sucrose, fructose, preferred sugar alcohol is to be selected from following one or more mannitol, lactose.
6. according to the Lu Laxi ketone tablet of claim 1-5, wherein can also comprise one or more and be selected from following filler: starch, dextrin, microcrystalline Cellulose, modified starch.Exemplarily, this filler can account for the 5-50% of tablet weight.
7. according to the Lu Laxi ketone tablet of claim 1-6, wherein can also comprise one or more and be selected from following adjuvant: binding agent, lubricant, fluidizer, its amount accounts for the 1-20% of tablet weight.Described binding agent for example can be a water-soluble polymer.Said lubricant is magnesium stearate, stearic acid, zinc stearate, liquid Paraffin, Polyethylene Glycol, hydrogenated vegetable oil or its combination for example.Said fluidizer is silicon dioxide, silica sol, micropowder silica gel, Pulvis Talci etc. or its combination for example.
8. according to the Lu Laxi ketone tablet of claim 1-7, wherein the mean diameter of Lu Laxi ketone is 0.1-8um, and further, this tablet is the tablet of coating.
9. according to the Lu Laxi ketone tablet of claim 1-8, wherein the amount of Lu Laxi ketone is 10 ~ 160mg in each tablet.
10. prepare the method for the Lu Laxi ketone tablet of claim 1-9, it comprises the steps: Lu Laxi ketone, sugar alcohol and part or all low-substituted hydroxypropyl cellulose, mix homogeneously; Water or aquiferous ethanol for example concentration are lower than 40% ethanol as wetting agent or with binder aqueous solution this mixed powder is carried out wet granulation, drying; The low-substituted hydroxypropyl cellulose (if existence) that adds surplus, and optional lubricant, fluidizer, mix homogeneously; Tabletting; Randomly carry out coating.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006661A (en) * | 2012-12-06 | 2013-04-03 | 江苏先声药物研究有限公司 | Preparation containing lurasidone hydrochloride and preparation method thereof |
| CN103054824A (en) * | 2012-12-21 | 2013-04-24 | 北京万全德众医药生物技术有限公司 | Lurasidone hydrochloride orally-disintegrating tablet preparation and preparation method thereof |
| CN115554332A (en) * | 2021-12-17 | 2023-01-03 | 吉林省正和药业集团股份有限公司 | Lysimachia christinae hance tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184489A (en) * | 2005-05-26 | 2008-05-21 | 大日本住友制药株式会社 | pharmaceutical composition |
| CN101868228A (en) * | 2007-11-21 | 2010-10-20 | 大日本住友制药株式会社 | Orally disintegrating tablets |
| CN102078309A (en) * | 2011-01-22 | 2011-06-01 | 王定豪 | Dispersible tablet containing antipsychotic medicines and application thereof |
-
2012
- 2012-06-21 CN CN2012102068442A patent/CN102688209A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101184489A (en) * | 2005-05-26 | 2008-05-21 | 大日本住友制药株式会社 | pharmaceutical composition |
| CN101868228A (en) * | 2007-11-21 | 2010-10-20 | 大日本住友制药株式会社 | Orally disintegrating tablets |
| CN102078309A (en) * | 2011-01-22 | 2011-06-01 | 王定豪 | Dispersible tablet containing antipsychotic medicines and application thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006661A (en) * | 2012-12-06 | 2013-04-03 | 江苏先声药物研究有限公司 | Preparation containing lurasidone hydrochloride and preparation method thereof |
| CN103006661B (en) * | 2012-12-06 | 2015-02-18 | 江苏先声药物研究有限公司 | Preparation containing lurasidone hydrochloride and preparation method thereof |
| CN103054824A (en) * | 2012-12-21 | 2013-04-24 | 北京万全德众医药生物技术有限公司 | Lurasidone hydrochloride orally-disintegrating tablet preparation and preparation method thereof |
| CN115554332A (en) * | 2021-12-17 | 2023-01-03 | 吉林省正和药业集团股份有限公司 | Lysimachia christinae hance tablet and preparation method thereof |
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