CN104116741A - Vilazodone hydrochloride composition and preparation method thereof - Google Patents
Vilazodone hydrochloride composition and preparation method thereof Download PDFInfo
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- CN104116741A CN104116741A CN201310146602.3A CN201310146602A CN104116741A CN 104116741 A CN104116741 A CN 104116741A CN 201310146602 A CN201310146602 A CN 201310146602A CN 104116741 A CN104116741 A CN 104116741A
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- Prior art keywords
- vilazodone hydrochloride
- microcarrier
- preparation
- surfactant
- vilazodone
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- RPZBRGFNBNQSOP-UHFFFAOYSA-N vilazodone hydrochloride Chemical compound Cl.C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 RPZBRGFNBNQSOP-UHFFFAOYSA-N 0.000 title claims abstract description 69
- 229960003381 vilazodone hydrochloride Drugs 0.000 title claims abstract description 68
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 239000007787 solid Substances 0.000 claims abstract description 11
- 239000002671 adjuvant Substances 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 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 6
- 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 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
- 235000010355 mannitol Nutrition 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 5
- 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 4
- 229920000858 Cyclodextrin Polymers 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical class C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 150000003904 phospholipids Chemical class 0.000 claims description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 claims description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
- 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 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000008119 colloidal silica Substances 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 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 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 238000007046 ethoxylation reaction Methods 0.000 claims description 2
- 239000002563 ionic surfactant Substances 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000002736 nonionic surfactant Substances 0.000 claims description 2
- MVLVMROFTAUDAG-UHFFFAOYSA-N octadecanoic acid ethyl ester Natural products CCCCCCCCCCCCCCCCCC(=O)OCC MVLVMROFTAUDAG-UHFFFAOYSA-N 0.000 claims description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 8
- 238000000338 in vitro Methods 0.000 abstract description 5
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 2
- 238000001727 in vivo Methods 0.000 abstract 1
- 229940001789 viibryd Drugs 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 22
- 239000002775 capsule Substances 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000007907 direct compression Methods 0.000 description 5
- 229920001983 poloxamer Polymers 0.000 description 5
- 229920001214 Polysorbate 60 Polymers 0.000 description 4
- 208000024714 major depressive disease Diseases 0.000 description 4
- 229960003740 vilazodone Drugs 0.000 description 4
- SGEGOXDYSFKCPT-UHFFFAOYSA-N vilazodone Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 SGEGOXDYSFKCPT-UHFFFAOYSA-N 0.000 description 4
- 238000005550 wet granulation Methods 0.000 description 4
- -1 5-[ 4-[ 4-(5-cyano-1 H-indol--3-yl) butyl ]-1-piperazinyl ]-2-benzofuran oxamides Chemical class 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical group OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 206010020765 hypersomnia Diseases 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 229940044519 poloxamer 188 Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 229920002511 Poloxamer 237 Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920002700 Polyoxyl 60 hydrogenated castor oil Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000012826 adjustment disease Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000002328 demineralizing effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
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- 238000002798 spectrophotometry method Methods 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a vilazodone hydrochloride composition and a preparation method thereof. The composition includes vilazodone hydrochloride, a microcarrier and pharmaceutically acceptable excipients for an oral solid preparation. The preparation method is as below: mixing and crushing vilazodone hydrochloride and the microcarrier, and evenly mixing the mixture with pharmaceutically acceptable excipients for oral solid preparation. The obtained composition preparation has greatly improved dissolution in vitro, and in vivo bioavailability reaching bioequivalence to VIIBRYD.
Description
Technical field
The present invention relates to pharmaceutical composition containing Vilazodone Hydrochloride and preparation method thereof, belong to medical technical field.
Background technology
Along with social development, the pressure of the aspect such as spirit, psychology that fast pace brings, the sickness rate of depression obviously increases.Depression comprises the polytypes such as single phase property depression (being major depressive disorder and dysthymia), adjustment disorder, slight depression, season affective disorders, manic depression; wherein major depressive disorder claims again major depression obstacle, and its symptom comprises: depressed, interest reduction, body weight or the appetite of daily routines are obviously declined, insomnia or hypersomnia, be on tenterhooks/pace that (psychomotor agitation), feeling of fatigue or hypersomnia, sense of guilt or oneself belittle, suicidal thought.After morbidity, can affect patient's work, sleep, study, diet and recreation.
Vilazodone Hydrochloride (vilazodone hydrochloride) has the structure as formula I, chemistry is by name: 5-［ 4-［ 4-(5-cyano-1 H-indol--3-yl) butyl ］-1-piperazinyl ］-2-benzofuran oxamides hydrochlorate, for first indolyl amine antidepressants, belong to selective serotonin reuptake inhibitor and 5-HT
1Aacceptor portion agonist.
Existing document is more extensive for the research of Vilazodone Hydrochloride crystal formation, wherein notification number is in the patent documentation of CN100384841C, CN101139345B, all to have given openly for the multiple crystal habit form of Vilazodone Hydrochloride, comprises Vilazodone Hydrochloride solvate crystal formation, Vilazodone Hydrochloride hydrate crystal forms and Vilazodone Hydrochloride dehydration crystal formation, vilazodone dihydrochloride crystal formation, amorphous hydrochloric acid vilazodone.The present invention's following " crystal formation " classification is the class definition according to each crystal formation in CN100384841C document.
FDA (Food and Drug Adminstration) is in approval on January 21st, 2011 Vilazodone Hydrochloride tablet (trade name
) being used for the treatment of adult's major depressive disorder, prior art shows that Vilazodone Hydrochloride crystalline form IV has the character such as stripping relatively preferably,
what adopt that is to say Vilazodone Hydrochloride crystalline form IV.The dissolution properties difference of Vilazodone Hydrochloride different crystal forms is larger, the stripping of the Vilazodone Hydrochloride crystal formation except above-mentioned crystalline form IV is poor, be difficult to be used as preparation medicine, conventional preparation technique means are difficult to the preparation In Vitro Dissolution of each crystal formation to reach unanimously, and these means comprise: reduce particle diameter, pH adjusting agent, solubilizing agent, solid dispersion etc.
In view of the stripping problem of Vilazodone Hydrochloride crystal formation except above-mentioned crystalline form IV, and Vilazodone Hydrochloride great value pharmaceutically, be very necessary for Vilazodone Hydrochloride crystal formation compositions and preparation method research.The present invention, just by the application of several formulations means, has solved the problems referred to above, makes the solid preparation of Vilazodone Hydrochloride different crystal forms, reached with
stripping consistent, and in animal body with
bioequivalent effect.
Summary of the invention
The definition of Vilazodone Hydrochloride different crystal forms of the present invention is consistent with the definition of Vilazodone Hydrochloride different crystal forms in patent CN100384841C.
One of object of the present invention is to provide a kind of Vilazodone Hydrochloride compositions, to solve the low problem of bioavailability in other each crystal formation poor solubility beyond demineralizing acid vilazodone crystalline form IV, body, improves bioavailability in dissolution in vitro and body.
Vilazodone Hydrochloride compositions of the present invention is achieved through the following technical solutions:
Said composition comprises Vilazodone Hydrochloride, is total to microcarrier and the pharmaceutically acceptable adjuvant of oral solid formulation.Wherein said microcarrier altogether refers in the present composition and mixes in advance common micronized carrier with Vilazodone Hydrochloride, the effect that it plays Vilazodone Hydrochloride stripping in promotion compositions, improves bioavailability.
Further, Vilazodone Hydrochloride is Vilazodone Hydrochloride crystal formation, comprises the Vilazodone Hydrochloride crystal formation except crystalline form IV.
Further again, the weight ratio of microcarrier and Vilazodone Hydrochloride is 0.1～7:1 altogether, and preferred weight ratio is 0.5～5:1.
Further again, altogether microcarrier is wherein one or more of cyclodextrin, cyclodextrin derivative, lactose, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone.Described cyclodextrin derivative is selected from betacyclodextrin, HYDROXYPROPYL BETA-CYCLODEXTRIN.
Further again, the pharmaceutically acceptable adjuvant of oral solid formulation comprises filler, disintegrating agent, lubricant, fluidizer.Wherein filler is selected from one or more in lactose, mannitol, microcrystalline Cellulose, starch, cellulose-lactose, mannitol-starch, starch-lactose; Disintegrating agent is selected from one or more in dried starch, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose; Fluidizer is selected from one or both of silicon dioxide, colloidal silica; Lubricant is selected from one or more in magnesium stearate, Pulvis Talci, polyethylene glycol 6000.
Further again, in compositions, each amounts of components accounts for the ratio of composition total weight and is: Vilazodone Hydrochloride: 5%～12%, and microcarrier altogether: 1%～80%, filler: 10%～80%, disintegrating agent: 0.1%～5%; Lubricant: 0.1%～3%, fluidizer: 0.1%～3%.The ratio that preferred each amounts of components accounts for composition total weight is: Vilazodone Hydrochloride 8%～10%, altogether microcarrier: 5%～70%, and filler: 10%～60%, disintegrating agent: 0.5%～4%, lubricant: 0.5%～2.5%, fluidizer: 0.5%～2.5%.
Further again, described compositions can also add surfactant, and described surfactant comprises ionic surfactant and nonionic surfactant.
Further again, surfactant is selected from one or more of sodium lauryl sulphate, phospholipid, poloxamer class, GREMAPHOR GS32 class, ethoxylation polysorbate esters, poly-hydroxy stearic acid ethyl ester apoplexy due to endogenous wind, one or more in preferably sodium dodecyl sulfate, phospholipid, Pluronic/Lutrol F 44, PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108, poloxamer188, polyoxyethylene sorbitan monoleate, polysorbate 60, polysorbate 40, polysorbate 20, Cremophor EL, Cremophor RH40, Cremophor RH60.
Further again, the ratio that the consumption of surfactant accounts for composition total weight is: 0.05%～10%, and preferred consumption is 0.5%～8%.
The preparation method that another object of the present invention is to provide above-mentioned Vilazodone Hydrochloride compositions, feature is as follows: Vilazodone Hydrochloride is pulverized after microcarrier mixing together, mixing homogeneously with the pharmaceutically acceptable adjuvant of oral solid formulation, made tablet or capsule.
Further again, Vilazodone Hydrochloride together microcarrier mixes, and being crushed to particle diameter is 1～20 μ m.
Further again, can also together after microcarrier co-grinding, add alcoholic solution or the aqueous solution of surfactant at Vilazodone Hydrochloride, mix homogeneously with the pharmaceutically acceptable medium of oral solid formulation again through disperseing, after dry, make tablet or capsule.
In addition, Vilazodone Hydrochloride together the grinding mode of the mixture of microcarrier comprise grind, comminution by gas stream etc., can adopt the equipment such as ball mill, jet mill, colloid mill to carry out.The technique of making tablet or capsule comprises wet granulation, dry granulation, direct compression, the direct filled capsules of powder, particles filled capsule etc.
Advantage of the present invention is, has overcome prior art defect, has solved in prior art the In Vitro Dissolution problem of other Vilazodone Hydrochloride crystal formation preparations except crystalline form IV, and has improved bioavailability in composition.In addition, in the present composition, also can add surfactant, can solve better stripping problem.
Brief description of the drawings
Fig. 1 embodiment 1-8 prepare sample with
stripping curve contrast (0.1mol/L hydrochloric acid solution is medium).Fig. 2 embodiment 1-8 prepare sample with
stripping curve contrast (acetum that volume fraction is 0.1% is medium).
Fig. 3 embodiment 1-8 prepare sample with
stripping curve contrast (water is medium).
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further elaborated, but do not limit the present invention.
The present invention's Vilazodone Hydrochloride used refers to Vilazodone Hydrochloride crystal formation.
The patent documentation (24th～29 pages of description) that following Vilazodone Hydrochloride different crystal forms used is CN100384841C according to notification number is prepared gained, and other agents useful for same are commercially available obtaining.
Embodiment 1
The preparation of table 1 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride powder particle diameter to 5 μ m, to mix homogeneously with other adjuvants in prescription, direct compression makes tablet or the direct fill of powder becomes capsule.
Embodiment 2
The preparation of table 2 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride powder particle diameter to 5 μ m, mix homogeneously with other adjuvants except silicon dioxide, magnesium stearate in prescription, add the aqueous solution of polyoxyethylene sorbitan monoleate to granulate, after dry, granulate, add silicon dioxide, magnesium stearate to mix, tabletting is made tablet.
Embodiment 3
The preparation of table 3 Vilazodone Hydrochloride tablets/capsules
Preparation process: powder particle diameter to 20 μ m after Vilazodone Hydrochloride mixes with lactose, betacyclodextrin, to mix homogeneously with other adjuvants in prescription, direct compression makes tablet or the direct fill of powder becomes capsule.
Embodiment 4
The preparation of table 4 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride is crushed to particle diameter 15 μ m after mixing with mannitol, adds the alcoholic solution of phospholipid, after disperseing, being dried, mixs homogeneously with other adjuvants in prescription, and after wet granule compression tablet is made tablet or wet granulation, fill becomes capsule.
Embodiment 5
The preparation of table 5 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride is crushed to particle diameter 10 μ m after mixing with polyvinylpolypyrrolidone, adds the aqueous solution of poloxamer188, after disperseing, being dried, mixs homogeneously with other adjuvants in prescription, and direct compression makes tablet or the direct fill of powder becomes capsule.
Embodiment 6
The preparation of table 6 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride is crushed to particle diameter 8 μ m after mixing with mannitol, mixs homogeneously with other adjuvants in prescription, and wet granulation is made tablet or Sprinkle Caps.
Embodiment 7
The preparation of table 7 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride is crushed to particle diameter after mixing with HYDROXYPROPYL BETA-CYCLODEXTRIN be 5 μ m, add the aqueous solution of polyoxyethylene sorbitan monoleate, after disperseing, being dried, mix homogeneously with other adjuvants in prescription, direct compression makes tablet or the direct fill of powder becomes capsule.
Embodiment 8
The preparation of table 8 Vilazodone Hydrochloride tablets/capsules
Preparation process: Vilazodone Hydrochloride is crushed to particle diameter 2 μ m after mixing with microcrystalline Cellulose, adds the alcoholic solution of Cremophor RH40, after disperseing, being dried, mixs homogeneously with other adjuvants in prescription, and wet granulation is made tablet or capsule.
Embodiment 9 dissolutions are investigated
Press 2010 editions annex of Chinese Pharmacopoeia (annex X C), adopt oar method, 60 revs/min of rotating speeds, 37 ± 0.5 DEG C of temperature, respectively taking 0.1mol/L hydrochloric acid solution, 0.1%(volume fraction) acetum and water is as medium, determined by ultraviolet spectrophotometry dissolution, result shows: sample 1 and 2 is in 0.1%(volume fraction) in acetic aid medium stripping still can, but stripping is lower in 0.1mol/L hydrochloric acid and water, sample 3～8 with
in Vitro Dissolution in different medium, all reach unanimously (accompanying drawing 1,2,3).
Embodiment 10 pharmacokinetics tests
Self-control tablet with
pharmacokinetics comparison is carried out in agent, adopts once dog PK test under feed state.Get 8 Beagle dogs, male and female half and half.Experiment adopts two stage binary cycles to intersect, by own control contrived experiment scheme.
Pharmacokinetic parameter after table 9Beagle dog oral administration vilazodone tablet (40mg/ sheet)
Result shows, sample 1 and 2 and
biological inequivalence, T
maxthere is significant difference (P>0.05) through non parametric method inspection; Sample 3～8 with
bioequivalence, T
maxthere is no significant difference (P>0.05) through non parametric method inspection.
Claims (10)
1. a Vilazodone Hydrochloride compositions, is characterized in that: said composition comprises Vilazodone Hydrochloride, is total to microcarrier and the pharmaceutically acceptable adjuvant of oral solid formulation.
2. compositions according to claim 1, is characterized in that: microcarrier is selected from one or more in lactose, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, cyclodextrin and derivant thereof altogether.
3. compositions according to claim 1, is characterized in that: the weight ratio of microcarrier and Vilazodone Hydrochloride is altogether: 0.1～7:1, preferably 0.5-5:1.
4. compositions according to claim 1, is characterized in that: the pharmaceutically acceptable adjuvant of described oral solid formulation comprises filler, disintegrating agent, lubricant, fluidizer; The ratio that each amounts of components accounts for composition total weight is: Vilazodone Hydrochloride 5%～12%, microcarrier 1%～80% altogether, filler 10%～80%, disintegrating agent 0.1%～5%, lubricant 0.1%～3%, fluidizer 0.1%～3%; The ratio that preferred each amounts of components accounts for composition total weight is: Vilazodone Hydrochloride 8%～10%, altogether microcarrier: 5%～70%, and filler: 10%～60%, disintegrating agent: 0.5%～4%, lubricant: 0.5%～2.5%, fluidizer: 0.5%～2.5%.
5. compositions according to claim 4, it is characterized in that: described filler is selected from lactose, mannitol, microcrystalline Cellulose, starch, cellulose-lactose, mannitol-starch, one or more in starch-lactose, described disintegrating agent is selected from dried starch, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone, one or more in cross-linking sodium carboxymethyl cellulose, described fluidizer is selected from silicon dioxide, one or both in colloidal silica, described lubricant is selected from magnesium stearate, Pulvis Talci, one or more in polyethylene glycol 6000.
6. according to the compositions described in any one in claim 1 to 5, it is characterized in that: the ratio that also can add surfactant, the consumption of described surfactant to account for composition total weight is: 0.05%～10%, preferably 0.5%～8%.
7. compositions according to claim 6, it is characterized in that: surfactant comprises ionic surfactant and nonionic surfactant one or more of preferred phospholipid, sodium lauryl sulphate, poloxamer class, GREMAPHOR GS32 class, ethoxylation polysorbate esters and poly-hydroxy stearic acid ethyl ester apoplexy due to endogenous wind.
8. a method of preparing compositions claimed in claim 1, is characterized in that, Vilazodone Hydrochloride is pulverized after microcarrier mixing together, then mixed homogeneously with the pharmaceutically acceptable adjuvant of oral solid formulation.
9. preparation method according to claim 8, is characterized in that: Vilazodone Hydrochloride together microcarrier to be crushed to particle diameter be 1～20 μ m after mixing.
10. preparation method according to claim 9, it is characterized in that: can also be at Vilazodone Hydrochloride together after microcarrier co-grinding, add alcoholic solution or the aqueous solution of surfactant, after disperseing, being dried, mix homogeneously with the pharmaceutically acceptable medium of oral solid formulation again.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105125512A (en) * | 2015-09-09 | 2015-12-09 | 山东大学 | Crystal V-type puerarin tablets and preparation method thereof |
| CN106667939A (en) * | 2017-02-14 | 2017-05-17 | 万全万特制药（厦门）有限公司 | Orally disintegrating tablet containing vilazodone hydrochloride and preparation method thereof |
| WO2018082557A1 (en) * | 2016-11-02 | 2018-05-11 | Sunshine Lake Pharma Co., Ltd. | Vilazodone inclusion complexes, compositions and preparation thereof |
| WO2020119698A1 (en) * | 2018-12-13 | 2020-06-18 | 广东东阳光药业有限公司 | Vilazodone solid dispersion and preparation method therefor |
| CN111346097A (en) * | 2018-12-22 | 2020-06-30 | 江苏先声药业有限公司 | Composition and preparation method thereof |
| CN114652671A (en) * | 2020-12-23 | 2022-06-24 | 上海博志研新药物技术有限公司 | Vilazodone pharmaceutical composition, preparation method and application thereof |
| WO2023098745A1 (en) * | 2021-11-30 | 2023-06-08 | 广东东阳光药业有限公司 | Vilazodone composition, pharmaceutical preparation thereof, preparation therefor, and use thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102249979A (en) * | 2011-07-12 | 2011-11-23 | 上海开义医药化工有限公司 | Method for preparing 3-(4-chlorobutyryl)-1H-indole-5-methylcyanogen |
| CN102267985A (en) * | 2011-06-15 | 2011-12-07 | 上海医药工业研究院 | Preparation method for vilazodone and hydrochloride thereof |
| CN102949364A (en) * | 2011-08-30 | 2013-03-06 | 天津药物研究院 | Sustained release tablet containing effective component hydrochloric acid vilazodone |
-
2013
- 2013-04-24 CN CN201310146602.3A patent/CN104116741B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102267985A (en) * | 2011-06-15 | 2011-12-07 | 上海医药工业研究院 | Preparation method for vilazodone and hydrochloride thereof |
| CN102249979A (en) * | 2011-07-12 | 2011-11-23 | 上海开义医药化工有限公司 | Method for preparing 3-(4-chlorobutyryl)-1H-indole-5-methylcyanogen |
| CN102949364A (en) * | 2011-08-30 | 2013-03-06 | 天津药物研究院 | Sustained release tablet containing effective component hydrochloric acid vilazodone |
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| CN105125512A (en) * | 2015-09-09 | 2015-12-09 | 山东大学 | Crystal V-type puerarin tablets and preparation method thereof |
| US11517569B2 (en) | 2016-11-02 | 2022-12-06 | Sunshine Lake Pharma Co., Ltd. | Vilazodone inclusion complexes, compositions and preparation thereof |
| WO2018082557A1 (en) * | 2016-11-02 | 2018-05-11 | Sunshine Lake Pharma Co., Ltd. | Vilazodone inclusion complexes, compositions and preparation thereof |
| CN109922807A (en) * | 2016-11-02 | 2019-06-21 | 广东东阳光药业有限公司 | Vilazodone inclusion compound and combinations thereof and preparation method |
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| WO2020119698A1 (en) * | 2018-12-13 | 2020-06-18 | 广东东阳光药业有限公司 | Vilazodone solid dispersion and preparation method therefor |
| CN111346097A (en) * | 2018-12-22 | 2020-06-30 | 江苏先声药业有限公司 | Composition and preparation method thereof |
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