CN102949364A - Sustained release tablet containing effective component hydrochloric acid vilazodone - Google Patents
Sustained release tablet containing effective component hydrochloric acid vilazodone Download PDFInfo
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- CN102949364A CN102949364A CN2011102511084A CN201110251108A CN102949364A CN 102949364 A CN102949364 A CN 102949364A CN 2011102511084 A CN2011102511084 A CN 2011102511084A CN 201110251108 A CN201110251108 A CN 201110251108A CN 102949364 A CN102949364 A CN 102949364A
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- sustained release
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- vilazodone
- hydrochloric acid
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Abstract
The invention discloses a sustained release tablet containing an effective component hydrochloric acid vilazodone. The sustained release tablet is prepared from the effective component hydrochloric acid vilazodone and sustained release materials; the weight ratio of effective component hydrochloric acid vilazodone to sustained release materials is (1: 0.2)-(1: 20), preferably (1:0.5)-(1:10); and the sustained release material used by the sustained release tablet is one or a combination of several of guar gum, xanthan gum, acrylic resin and cellulose. The hydrochloric acid vilazodone has the characteristics of lasting functions, low toxic and side effects and less medicine-taking times; the release degree in vitro of the sustained release tablet is 8-24 hours; the blood medicine concentration is stable; the occurrence ratio of poor reaction is reduced; the curative effect of the medicines is improved; and the pain of patients is relieved.
Description
Technical field
The invention belongs to medical technical field, more particularly, is a kind of oral slow releasing tablet that contains effective composition Vilazodone Hydrochloride, the treatment of the major depressive disorder that is mainly used in being grown up.
Background technology
Nomenclature of drug: Vilazodone Hydrochloride
English name: Vilazodone Hydrochloride
Chemical name:
5-[4-[4-(5-Cyanoindol-3-yl)butyl]piperazin-1-yl]benzofuran-2-carboxamidehydrochloride
Structural formula:
Molecular formula: C
26H
27N
5O
2HCl
Molecular weight: 477.99
Depression (depression) is a kind of common psychotic mental illness.Mainly be because black polycholia in the human body, enter in the brain and destroy the cause of their activities.World Health Organization's investigation discovery, depression whole world sickness rate is about 11%, has become at present the fourth-largest disease in the world.It may become the human second largest illness that is only second to cardiovascular and cerebrovascular disease to expect the year two thousand twenty.A joint study of World Health Organization (WHO), the World Bank and Harvard University shows, depression has become the second serious disease of Chinese disease burden.The major depression obstacle is degree of weighing depression again, and symptom comprises: depressed, to interest reduction, body weight or the appetite of daily routines obviously descend, insomnia or hypersomnia, be on tenterhooks/pace (psychomotor agitation), feeling of fatigue increase the weight of, sense of guilt or the oneself belittles, suicidal thought.Can affect patient's work, sleep, study, diet and recreation after the morbidity.Generally speaking, severe depression patient is equal possibility Recrudesce throughout one's life, but some patient may not can repeat outbreak.Serious depression has nearly 15% homicide rate, and the new drug of therefore researching and developing effective Cure of depression is particularly important.
FDA (Food and Drug Adminstration) (FDA) approval on January 21st, 2011 Vilazodone Hydrochloride (trade name Viibryd) conventional tablet is used for the treatment of adult's major depressive disorder.Viibryd is by PGxHealth, New Haven, and Conn produces.Vilazodone Hydrochloride belongs to 5-hydroxy tryptamine 1A (5-HT
1A) the double activity medicine of partial agonist and selectivity 5-hydroxy tryptamine (5-HT) reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), also be first indolyl amine novel antidepressant.Because this medicine belongs to novel antidepressant, it is predicted, the more traditional SSRI class antidepressant of side reaction of the mechanism of action of Viibryd uniqueness, quick and clear and definite clinical efficacy, less sexual function aspect has better prospect.Not yet go on the market in China at present.
The mechanism of vilazodone antidepressant effect is understood fully, but is considered to can actively increase relevant with its 5-hydroxy tryptamine by selectivity inhibition serotonin reuptake transporter in CNS.Vilazodone also is the partial agonist of 5-hydroxy tryptamine energy 5-HT1A receptor, vilazodone is combined (Ki=0.1nM) with 5-HT reuptake sites high-affinity, but does not have high-affinity with norepinephrine (Ki=56nM) or dopamine (Ki=37nM) reuptake sites.The vilazodone highly selective suppresses 5-HT and absorbs (IC again
50=1.6nM).In addition, vilazodone also with 5-HT
1AThe receptor high-affinity is in conjunction with (IC
50=2.1nM), be 5-HT
1AAcceptor portion agonist.
The pharmacokinetics of vilazodone (dosage between 5mg-80mg time) is the dosage proportional relationship.The elimination of vilazodone is mainly by hepatic metabolism, and the terminal half-life was near 25 hours.When stable state, condition gives Viibryd 40mg lower every day on the feed, and the meansigma methods of Cmax is 156ng/ml, and the meansigma methods of AUC (0-24 hour) is 1645ngh/ml.The vilazodone concentration peak descends near 25 hours at meta 4-5 hour (Tmax) with the terminal half-life after the administration, with the absolute bioavailability of food be 72%.Give to increase the oral bioavailability (Cmax increases near 147-160%, and AUC increases near 64-85%) that gets with food (high fat or informal dinner).Vilazodone is widely distributed after absorption of human body, and the protein binding rate of nearly 96-99% is arranged.
External listing dosage form is conventional tablet at present, and commodity are called Viibryd, and specification is respectively 10mg, 20mg and 40mg.Vilazodone Hydrochloride be mainly used in the being grown up treatment of major depressive disorder, low dose of conventional tablet exists medication frequent, major depression patient's the shortcomings such as poor compliance; And the shortcomings such as blood concentration fluctuation was larger after also there was administration in conventional tablet, and toxic and side effects is larger are made slow releasing tablet with Vilazodone Hydrochloride and then can be overcome above numerous shortcoming, thereby improved patient's compliance, have improved the curative effect of medicine.Therefore the present invention has obvious clinical practice meaning.
Summary of the invention
The object of the invention is to, overcome the shortcoming of existing preparation technique with not enough, provide a kind of and have effect lastingly, toxic and side effects is low, the Vilazodone Hydrochloride slow releasing tablet that medicining times is few, this slow releasing tablet dissolution in vitro is slow release more than 8 hours, and blood drug level is steady, thereby brings into play better the pharmacological action of medicine.
Slow releasing tablet of the present invention is compared with existing listing dosage form and is had the following advantages:
(1) this medicine sustained release can reach more than 24 hours, can obviously reduce medicining times, improved patient's compliance;
(2) taking convenience, determined curative effect is released phenomenon without prominent, has reduced the incidence rate of untoward reaction;
(3) technical without difficult point, can adopt existing production line to finish, simple to operate, repeatability is good, need not special instruments and equipment, easily carries out industrialized great production.
The effective ingredient Vilazodone Hydrochloride slow releasing tablet that contains of the present invention is comprised of effective ingredient Vilazodone Hydrochloride and slow-release material.Wherein effective ingredient Vilazodone Hydrochloride and slow-release material weight ratio are 1: 0.2～1: 20, and preferred weight ratio is 1: 0.5～1: 10.
Described slow-release material is one or more the compositions in guar gum, xanthan gum, acrylic resin and the cellulose.Wherein acrylic resin is one or more the compositions in methacrylic acid and ethyl acrylate copolymer, methacrylic acid and methyl acrylate copolymer, ethyl acrylate, methyl methacrylate and the methacrylic acid chlorination trimethylamine groups ethyl ester copolymer.
Described cellulose is one or more the compositions in methylcellulose, ethyl cellulose, hydroxypropyl cellulose, the hydroxypropyl methylcellulose.
The present invention also comprises drug excipient commonly used in the preparation, such as filler, binding agent, lubricant etc., concrete evenly mixes with effective ingredient Vilazodone Hydrochloride, slow-release material by a certain percentage such as lactose, starch, polyvinylpyrrolidone, hypromellose, Polyethylene Glycol, medicinal alcohol, magnesium stearate, stearic acid, micropowder silica gel etc., makes slow releasing tablet by preparation conventional method vertical compression or wet granulation.
Description of drawings
Fig. 1 embodiment 1 vitro release is more than 8 hours;
Fig. 2 embodiment 2 vitro releases are more than 8 hours;
Fig. 3 embodiment 3 vitro releases are more than 12 hours;
Fig. 4 embodiment 4 vitro releases are more than 12 hours;
Fig. 5 embodiment 5 vitro releases are more than 24 hours;
Fig. 6 embodiment 6 vitro releases are more than 24 hours.
The specific embodiment
The following example is to further explanation of the present invention and explanation, but does not mean that it limits the scope of the invention by any way.
Embodiment 1 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 80 mesh sieves, for subsequent use.Take by weighing first recipe quantity adjuvant (removing hydroxypropyl cellulose 4000cp and magnesium stearate, micropowder silica gel) and the abundant mix homogeneously of principal agent, add binding agent soft material processed, 20 mesh sieves are granulated, after 55 ℃ of dryings, and 18 mesh sieve granulate.Add at last magnesium stearate, micropowder silica gel and hydroxypropyl cellulose mix homogeneously, tabletting behind the mensuration intermediate.
Embodiment 2 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 60 mesh sieves, for subsequent use.Take by weighing the recipe quantity principal agent successively with adjuvant guar gum, hypromellose, lactose, Pulvis Talci, the abundant mix homogeneously of magnesium stearate, measure direct compression behind the intermediate.
Embodiment 3 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 80 mesh sieves, for subsequent use.Take by weighing first recipe quantity adjuvant (removing hydroxypropyl cellulose 4000cp and Pulvis Talci, micropowder silica gel) and the abundant mix homogeneously of principal agent, add binding agent soft material processed, 20 mesh sieves are granulated, after 55 ℃ of dryings, and 18 mesh sieve granulate.Add at last Pulvis Talci, micropowder silica gel and hydroxypropyl cellulose mix homogeneously, tabletting behind the mensuration intermediate.
Embodiment 4 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 80 mesh sieves, for subsequent use.Take by weighing first the abundant mix homogeneously of recipe quantity adjuvant and principal agent, add binding agent soft material processed, 20 mesh sieves are granulated, after 55 ℃ of dryings, and 18 mesh sieve granulate.Add at last magnesium stearate, micropowder silica gel mix homogeneously, tabletting behind the mensuration intermediate.
Embodiment 5 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 60 mesh sieves, for subsequent use.Take by weighing the recipe quantity principal agent successively with adjuvant PVP K30, hydroxypropyl cellulose (K15M), hydroxypropyl cellulose (K100M), lactose, differential silica gel, the abundant mix homogeneously of magnesium stearate, measure direct compression behind the intermediate.
Embodiment 6 (1000 amounts)
Preparation technology:
Principal agent and adjuvant are crossed respectively 60 mesh sieves, for subsequent use.Take by weighing the recipe quantity principal agent successively with adjuvant hydroxypropyl cellulose (50cp), lactose, differential silica gel, the abundant mix homogeneously of magnesium stearate, measure direct compression behind the intermediate.
Embodiment 7
Vitro release assay method and condition with the Vilazodone Hydrochloride slow releasing tablet of the inventive method preparation:
Instrument: ZRS-8 medicament dissolution instrument
Rotating speed: 75 rev/mins
Temperature: 37 ℃
Solvent: front 2 hours is the 0.1mol/L hydrochloric acid solution, changes subsequently the pH6.8 phosphate buffer solution into.
Sampling during respectively at 1,2,4,6,8,12,16,24 hour, sample is measured (the vitro release measurement result sees Table 1) according to drug release determination method under the version Chinese Pharmacopoeia appendix X D item in 2010.
Measure through vitro release: embodiment 1 sustained-release tablets is more than 8 hours, embodiment 2 sustained-release tablets are more than 8 hours, embodiment 3 sustained-release tablets are more than 12 hours, embodiment 4 sustained-release tablets are more than 12 hours, embodiment 5 sustained-release tablets are more than 24 hours, and embodiment 6 sustained-release tablets are also more than 24 hours.Above-mentioned test determination result selects different slow-release materials as can be known, and prepared slow releasing tablet can both reach slow release effect in 8～24 hours, and release result is even, the not prominent phenomenon of releasing.Meet version Chinese Pharmacopoeia in 2010 about the guideline of slow releasing preparation.
Although the present invention has done detailed description in conjunction with the embodiment of self, clearly concerning the people that the art is familiar with, still can make other changes and improvements, can not depart from spirit of the present invention and protection domain.
Table 1 vitro release measurement result
Claims (7)
1. a slow releasing tablet that contains effective composition Vilazodone Hydrochloride it is characterized in that being comprised of effective ingredient Vilazodone Hydrochloride and slow-release material.
2. slow releasing tablet according to claim 1 is characterized in that effective ingredient Vilazodone Hydrochloride and slow-release material weight ratio are 1: 0.2～1: 20.
3. slow releasing tablet according to claim 2 is characterized in that effective ingredient Vilazodone Hydrochloride and slow-release material weight ratio are 1: 0.5～1: 10.
4. each described slow releasing tablet according to claim 1-3 is characterized in that described slow-release material is one or more the compositions in guar gum, xanthan gum, acrylic resin and the cellulose.
5. slow-release material according to claim 4 is characterized in that described acrylic resin is one or more the compositions in methacrylic acid and ethyl acrylate copolymer, methacrylic acid and methyl acrylate copolymer, ethyl acrylate, methyl methacrylate and the methacrylic acid chlorination trimethylamine groups ethyl ester copolymer.
6. slow-release material according to claim 4 is characterized in that described cellulose is one or more the compositions in methylcellulose, ethyl cellulose, hydroxypropyl cellulose, the hydroxypropyl methylcellulose.
7. each described slow releasing tablet according to claim 1-4 is characterized in that being used for the treatment of the purposes of adult's major depressive disorder aspect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102511084A CN102949364A (en) | 2011-08-30 | 2011-08-30 | Sustained release tablet containing effective component hydrochloric acid vilazodone |
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| CN2011102511084A CN102949364A (en) | 2011-08-30 | 2011-08-30 | Sustained release tablet containing effective component hydrochloric acid vilazodone |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211751A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Medical composition containing vilazodone and preparation method thereof |
| CN104116741A (en) * | 2013-04-24 | 2014-10-29 | 江苏先声药物研究有限公司 | Vilazodone hydrochloride composition and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0648767A1 (en) * | 1993-09-30 | 1995-04-19 | MERCK PATENT GmbH | Piperdine and piperazine derivatives which affect the C.N.S. |
| WO2000072832A2 (en) * | 1999-05-27 | 2000-12-07 | Merck Patent Gmbh | Novel use of 1-[4-(cyanoindol-3yl)butyl]-4-(carbamoyl-benzofuran-5yl)-piperazine and its physiologically acceptable salts |
| WO2005018676A1 (en) * | 2003-08-21 | 2005-03-03 | H. Lundbeck A/S | The combination of a serotonin reuptake inhibitor and a glycine transporter type 1 inhibitor for the treatment of depression |
| CN1671363A (en) * | 2002-06-07 | 2005-09-21 | 兰贝克赛实验室有限公司 | Extended release formulation of divalproex sodium |
| US20080293943A1 (en) * | 2005-04-26 | 2008-11-27 | Andreas Bathe | Process for the Preparation of 5-(4-[4-(5-Cyano-3-Indolyl)Butyl]-1-Piperazinyl)Benzofuran-2-Carboxamide |
| CN101679326A (en) * | 2007-03-07 | 2010-03-24 | 詹森药业有限公司 | Substituted phenoxy n-alkylated thiazoledinedione as estrogen related receptor-alpha modulators |
-
2011
- 2011-08-30 CN CN2011102511084A patent/CN102949364A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0648767A1 (en) * | 1993-09-30 | 1995-04-19 | MERCK PATENT GmbH | Piperdine and piperazine derivatives which affect the C.N.S. |
| WO2000072832A2 (en) * | 1999-05-27 | 2000-12-07 | Merck Patent Gmbh | Novel use of 1-[4-(cyanoindol-3yl)butyl]-4-(carbamoyl-benzofuran-5yl)-piperazine and its physiologically acceptable salts |
| CN1671363A (en) * | 2002-06-07 | 2005-09-21 | 兰贝克赛实验室有限公司 | Extended release formulation of divalproex sodium |
| WO2005018676A1 (en) * | 2003-08-21 | 2005-03-03 | H. Lundbeck A/S | The combination of a serotonin reuptake inhibitor and a glycine transporter type 1 inhibitor for the treatment of depression |
| US20080293943A1 (en) * | 2005-04-26 | 2008-11-27 | Andreas Bathe | Process for the Preparation of 5-(4-[4-(5-Cyano-3-Indolyl)Butyl]-1-Piperazinyl)Benzofuran-2-Carboxamide |
| CN101679326A (en) * | 2007-03-07 | 2010-03-24 | 詹森药业有限公司 | Substituted phenoxy n-alkylated thiazoledinedione as estrogen related receptor-alpha modulators |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211751A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Medical composition containing vilazodone and preparation method thereof |
| CN104116741A (en) * | 2013-04-24 | 2014-10-29 | 江苏先声药物研究有限公司 | Vilazodone hydrochloride composition and preparation method thereof |
| CN104116741B (en) * | 2013-04-24 | 2019-06-11 | 江苏先声药业有限公司 | Vilazodone Hydrochloride composition and preparation method thereof |
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Application publication date: 20130306 |