CN110384666A - A kind of method of wet granule compression tablet preparation dextrorotation Oxiracetam tablet - Google Patents
A kind of method of wet granule compression tablet preparation dextrorotation Oxiracetam tablet Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The present invention provides a kind of preparation methods of dextrorotation Oxiracetam tablet, this method is using particular crystalline form dextrorotation Oxiracetam as active constituent, it is made with auxiliary material through wet granule compression tablet technique, dextrorotation Oxiracetam does not stick easy to operate in tablet press machine or granulation pot inner wall, preparation process substantially in preparation process.Dextrorotation Oxiracetam tablet prepared by the present invention is unilateral smooth, and hardness is suitble to long-distance transport between 8.50-9.90kg, while dissolution rate is fast, and 30min is dissolved out completely substantially, and friability is lower than 0.5%.Preparation process of the present invention is simple, and the operating time is short, high production efficiency, is suitble to industrialized production.
Description
Technical field
The present invention relates to dextrorotation Oxiracetam tablets, and in particular to a kind of wet granule compression tablet preparation dextrorotation Oxiracetam piece
The method of agent.
Background technique
Oxiracetam (Oxiracetam), chemical name are Esomeprazole, most earlier than
It is listed by Italian ISFS.S.P.A company in Europe within 1987, is clinically widely used in light moderate vascular dementia, senile
It is dull-witted and and the diseases such as brain trauma caused by memory and disturbance of intelligence.Oxiracetam is nootropic agents of new generation, belongs to new
Pyrrolidinone compounds (ring GABOB) derivative of type.Cerebrovascular disease, cerebral injury, brain tumor (postoperative), intracranial infection, dementia, brain are become
Property disease etc. has good efficacy.Studies at home and abroad show that Oxiracetam has higher pharmacological activity and significant compared with Piracetam
Clinical efficacy.Oxiracetam has two kinds of isomers of a chiral centre, levo-oxiracetam and dextrorotation Oxiracetam.It is Chinese special
Sharp CN101766596A disclosed a kind of using dextrorotation Oxiracetam as the solid pharmaceutical preparation of active constituent in 2009, and it includes dextrorotation
Oxiracetam and pharmaceutically acceptable auxiliary material, this method replace Oxiracetam in the prior art with dextrorotation Oxiracetam, from
And enhance the pharmacological activity of anti-senile dementia.Chinese patent CN102204904A is in report levo-oxiracetam in 2010 to old
The curative effect of disease such as dementia, cognition dysfunction mix better than Oxiracetam and select body and dextrorotation Oxiracetam, and dextrorotation Oxiracetam
It is poor to curative effect of disease such as senile dementia, cognition dysfunctions or even invalid.Chinese patent CN106166150A is in 2016 annual reports
Road dextrorotation Oxiracetam has preferable activity in terms of anti-epileptic, especially as treatment epilepsy generalized seizures, epilepsy portion
Divide property breaking-out and the effect of status epilepticus drug obvious, is expected to exploitation into novel low-toxicity antiepileptic.Dextrorotation Aura west
It is smooth to draw moist relatively strong, it is easy to stick in tablet press machine or granulation pot inner wall in wet granule compression tablet, it is difficult to operate in granulation or tabletting
It spends larger, is unfavorable for the development of preparation process.
Summary of the invention
In order to solve the problems in the prior art, the purpose of the present invention is to provide a kind of systems of dextrorotation Oxiracetam tablet
Preparation Method, this method use specific crystal formation dextrorotation Oxiracetam for active constituent, and the auxiliary material with special ratios is through wet granulation pressure
Dextrorotation Oxiracetam tablet is made in blade technolgy, and dextrorotation Oxiracetam is not sticked on tablet press machine substantially or pelletized in pot in preparation process
Wall, preparation process are easy to operate.
To achieve the purpose of the present invention, the present invention uses following technical scheme.
The preparation method of dextrorotation Oxiracetam tablet of the present invention, preparation process include stock, wet granulation and tabletting
Step, it is characterised in that: the stock is to weigh each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material of crystal form
80 meshes are crossed respectively with filler, disintegrating agent；Adhesive is configured to the binder solution of 3-15%, it is spare as adhesive；
The wet granulation mixes 3-8min for screened material to be added in wet granulator with 100-350 revs/min of speed, then
Binder solution softwood, the granulation of 16 meshes, 20-40 DEG C of dry 40-70min, 18 mesh sieves are added；The tabletting is that will make
Standby dextrorotation Oxiracetam particle, be put into after mixing with lubricant and corrigent it is tabletted in rotary tablet machine, turn
Platform 15~30r/min of revolving speed, stuffing pressure are 30~40N, and depth of fill is 10~20mm.
Crystal form dextrorotation Aura west in dextrorotation Oxiracetam tablet prepared by the present invention containing 70~125 parts by weight
Smooth, 5~30 parts by weight of filler, 5-25 part by weight of disintegrant, 3-10 parts by weight of binder, 1-3 parts by weight lubricant, 1-3 weight
Measure part corrigent.The dextrorotation Oxiracetam of crystal form of the present invention is radiated using Cu-K α, and obtained X-ray powder spreads out
Penetrate spectrum 2 θ of angle of reflection be 14.14 ± 0.2 °, 17.76 ± 0.2 °, 18.72 ± 0.2 °, 20.16 ± 0.2 °, 21.20 ± 0.2 °,
21.52 ± 0.2 °, 24.17 ± 0.2 °, 25.88 ± 0.2 ° have diffraction maximum.
Preferably, the crystal form dextrorotation containing 85~110 parts by weight in dextrorotation Oxiracetam tablet prepared by the present invention
Oxiracetam, 10~30 parts by weight of filler, 8-20 part by weight of disintegrant, 5-10 parts by weight of binder, 1-3 parts by weight lubrication
Agent, 1-2 parts by weight corrigent.
Filler of the present invention is selected from calcium monohydrogen phosphate, dextrin, lactose, mannitol, aluminium hydroxide, magnesium carbonate, crystallite
Cellulose, fructose, sorbierite, sucrose, starch and combinations thereof；It is preferred that dextrin, mannitol, microcrystalline cellulose, sorbierite, starch and
A combination thereof.The disintegrating agent is selected from croscarmellose sodium, crospovidone, Sodium Hydroxymethyl Stalcs, low substituted hydroxy-propyl
Cellulose, pregelatinized starch or combinations thereof；It is preferred that croscarmellose sodium, crospovidone, low substituted hydroxy-propyl fiber
Element.Adhesive be selected from hydroxypropyl cellulose, hypromellose, copolyvidone, povidone, starch slurry, methylcellulose or
A combination thereof；The lubricant is selected from magnesium stearate, superfine silica gel powder, talcum powder, hydrogenated vegetable oil or combinations thereof；The corrigent choosing
From aspartame, xylitol, Sucralose, glycyrrhizic acid monoammonium S or combinations thereof.
The dextrorotation Oxiracetam of crystal form of the present invention is made using following steps: dextrorotation Oxiracetam is dissolved in
In the hydrochloric acid that mass concentration is >=30%, the weight ratio of hydrochloric acid and dextrorotation Oxiracetam is 1~3:1, is stirred continuously, is warming up to 50
Active carbon decoloring is added with adjusting PH with base value to 7~8 in~80 DEG C of 1~5h of heat preservation, and filtering moves to filtrate in crystallizer, Xiang Jie
Stream plus the acetonitrile of hydrochloric acid volume 1/3~1/2 in brilliant device, 1~3h of growing the grain are filtered, filter residue is 30 then with adjusting PH with base value to 7~8
~40 DEG C, under conditions of relative humidity is 60-90% dry 3-8h to get；The alkali is that mass concentration is 10~20%
Sodium hydrate aqueous solution or potassium hydroxide aqueous solution.
Further, the dextrorotation Oxiracetam of crystal form of the present invention is made using following steps: by dextrorotation Aura
The western smooth mass concentration that is dissolved in is in >=30% hydrochloric acid, and the weight ratio of hydrochloric acid and dextrorotation Oxiracetam is 1~3:1, is stirred continuously, stirs
Mixing speed is 150r/min~350r/min, is warming up to 60~80 DEG C of 1~3h of heat preservation, and with adjusting PH with base value to 7~8, activity is added
Carbon decoloring, filtering, filtrate is moved in crystallizer, stream plus acetonitrile into crystallizer, and the volume of stream plus acetonitrile is hydrochloric acid volume
1/3~1/2, flow acceleration is 4~7mL/min, later 1~3h of growing the grain, the hydroxide for being then 10~20% with mass concentration
Sodium water solution tune pH value filters, filter residue is at 30~40 DEG C, relative humidity dry 3-5h under conditions of being 60-90%, i.e., to 7~8
?.
Specifically, the preparation method of above-mentioned dextrorotation Oxiracetam tablet, using following steps:
(1) preparation of the dextrorotation Oxiracetam of crystal form: it is >=30% salt that dextrorotation Oxiracetam, which is dissolved in mass concentration,
In acid, the weight ratio of hydrochloric acid and dextrorotation Oxiracetam is 1~3:1, is stirred continuously, and mixing speed is 150r/min~350r/
Min is warming up to 60~80 DEG C of 1~3h of heat preservation, with adjusting PH with base value to 7~8, active carbon decoloring is added, filtrate is moved to knot by filtering
In brilliant device, into crystallizer stream plus acetonitrile, stream plus acetonitrile volume be hydrochloric acid volume 1/3~1/2, flow acceleration be 4~
7mL/min, 1~3h of growing the grain, the sodium hydrate aqueous solution tune pH value for being then 10~20% with mass concentration are taken out to 7~8 later
Filter, filter residue is at 30~40 DEG C, and drying 3-5h is western to get the dextrorotation Aura of crystal form under conditions of relative humidity is 60-90%
It is smooth.
(2) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material of crystal form and filling
Agent, disintegrating agent cross 80 meshes respectively；Adhesive is configured to the binder solution of 3-15%, it is spare as adhesive；It will sieving
Material be added in wet granulator 3-8min mixed with 100-350 revs/min of speed, it is soft to add binder solution system
Material, the granulation of 16 meshes, 20-40 DEG C of dry 40-70min, 18 mesh sieves；
(3) tabletting: the dextrorotation Oxiracetam particle of preparation is put into rotatably after mixing with lubricant and corrigent
Tabletted in tablet press machine, turntable 15~30r/min of revolving speed, stuffing pressure is 30~40N, and depth of fill is 10~20mm.
The utility model has the advantages that
The present invention provides a kind of preparation method of dextrorotation Oxiracetam tablet, this method is difficult to understand with particular crystalline form dextrorotation
La Xitan (2 θ of angle of reflection be 14.14 ± 0.2 °, 17.76 ± 0.2 °, 18.72 ± 0.2 °, 20.16 ± 0.2 °, 21.20 ±
0.2 °, 21.52 ± 0.2 °, 24.17 ± 0.2 °, 25.88 ± 0.2 ° has diffraction maximum) it is active constituent, with specific ratio of adjuvant
It is made through wet granule compression tablet technique, dextrorotation Oxiracetam is not sticked substantially in tablet press machine or granulation pot inner wall, system in preparation process
Agent technological operation is convenient.Dextrorotation Oxiracetam tablet prepared by the present invention is unilateral smooth, and hardness is fitted between 8.50-9.90kg
Long-distance transport is closed, while dissolution rate is fast, 30min is dissolved out completely substantially, and friability is lower than 0.5%.Preparation process letter of the present invention
Single, the operating time is short, high production efficiency, is suitble to industrialized production.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to which indicated herein is that following embodiment is only used
In invention is further explained, it should not be understood as limiting the scope of the invention, person skilled in art can
To make some nonessential modifications and adaptations to the present invention according to aforementioned present invention content.The preparation process of crystal form of the present invention
In, it is filtered into conventional solid-liquid separate mode known in the art.Unless otherwise specified, number of the present invention is weight
Part, the percentage is mass percent.
Embodiment 1
Commercially available dextrorotation Oxiracetam 10g is dissolved in 32% hydrochloric acid of 20mL (w/w), 72 DEG C of heat preservation 80min is warming up to, adds
Enter 10% sodium hydrate aqueous solution (w/w) and adjust PH to 7.5,0.01g activity carbon decoloring is added, filtrate is moved to crystallizer by filtering
In, stream plus 15mL acetonitrile into crystallizer, flow acceleration 4mL/min, later growing the grain 120min, then extremely with adjusting PH with base value
8.0, it filters, filter residue obtains dextrorotation Oxiracetam crystalline solid in 30 DEG C, relative humidity dry 4h under conditions of being 75%.Test
Instrument condition: room temperature test, test condition are as follows: with Cu Ka are carried out using Bruker D2 PHASER powder diffractometerFor light source, voltage 30kV, electric current 10mA test 0.014 ° of step-length, scanning speed 0.1s/step, scanning range
5-40°(2θ).Through detecting, embodiment 1 prepare dextrorotation Oxiracetam crystal, 2 θ of angle of diffraction be 10.54 ± 0.2 °,
13.76±0.2°、14.14±0.2°、16.64±0.2°、17.76±0.2°、18.72±0.2°、20.16±0.2°、21.20
±0.2°、21.52±0.2°、23.25±0.2°、24.17±0.2°、25.88±0.2°、27.61±0.2°、28.57±
0.2 °, 29.24 ± 0.2 °, 31.40 ± 0.2 ° has diffraction maximum.By the dextrorotation Oxiracetam crystalline solid of acquisition be maintained at 60 DEG C with
In the drier of 92.5% humidity level, after 24 hours, hygroscopic capacity 0.03%.
Embodiment 2
Dextrorotation Oxiracetam 10g is dissolved in 33% hydrochloric acid of 20mL (w/w), 60 DEG C of heat preservation 100min are warming up to, is added
10% sodium hydrate aqueous solution (w/w) adjusts PH to 7.0, and 0.01g activity carbon decoloring is added, and filtering moves to filtrate in crystallizer,
Stream plus 10mL acetonitrile into crystallizer, flow acceleration 5mL/min, growing the grain 60min takes out then with adjusting PH with base value to 7.0 later
Filter, filter residue were both obtained in 40 DEG C, relative humidity dry 5h under conditions of being 85%.It is identified referring to the method for embodiment 1, embodiment 2
The dextrorotation Oxiracetam crystal that the dextrorotation Oxiracetam crystal of preparation is prepared with embodiment 1 is the phase isomorphism.By the dextrorotation of acquisition
Oxiracetam crystalline solid is maintained in 60 DEG C of driers with 92.5% humidity level, after 24 hours, hygroscopic capacity 0.05%.
Embodiment 3
Dextrorotation Oxiracetam 10g is dissolved in 30% hydrochloric acid of 30mL (w/w), 80 DEG C of heat preservation 60min are warming up to, is added
20% sodium hydrate aqueous solution (w/w) adjusts PH to 8.0, and 0.01g activity carbon decoloring is added, and filtering moves to filtrate in crystallizer,
Stream plus 10mL acetonitrile into crystallizer, flow acceleration 7mL/min, later growing the grain 180min, then with adjusting PH with base value to 8.0,
It filters, filter residue was both obtained in 30 DEG C, relative humidity dry 4h under conditions of being 75%.It identifies, implements referring to the method for embodiment 1
The dextrorotation Oxiracetam crystal that dextrorotation Oxiracetam crystal prepared by example 3 is prepared with embodiment 1 is the phase isomorphism.By the right side of acquisition
Rotation Oxiracetam crystalline solid is maintained in 60 DEG C of driers with 92.5% humidity level, and after 24 hours, hygroscopic capacity is
0.04%.
Embodiment 4
Prescription: 100 parts, 15 portions mannitol of dextrorotation Oxiracetam of the crystal form of reference 1 method of embodiment preparation, 5 parts
Sucrose, 10 parts of croscarmellose sodiums, 5 parts of hypromellose, 2 parts of talcum powder, 1 part of Sucralose.
Preparation process
(1) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material and sweet dew of crystal form
Alcohol, sucrose, croscarmellose sodium cross 80 meshes respectively；The hydroxypropyl that hypromellose is configured to 8% is fine
Plain solution is tieed up, it is spare as adhesive；Screened material is added in wet granulator and is mixed with 300 revs/min of speed
6min adds binder solution softwood, the granulation of 16 meshes, 30 DEG C of dry 60min, 18 mesh sieves；
(2) by the dextrorotation Oxiracetam particle of preparation, it tabletting: is put into rotation after mixing with talcum powder and Sucralose
It is tabletted in formula tablet press machine, turntable revolving speed 20r/min, stuffing pressure 35N, depth of fill 15mm.
Embodiment 5
Prescription: embodiment 1 prepare 110 parts, 20 parts sorbierites of crystal form dextrorotation Oxiracetam, 8 parts of pregelatinized starch,
5 parts of povidone, 2 parts of magnesium stearates, 1 part of xylitol.
Preparation process
(1) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material and sorb of crystal form
Alcohol, pregelatinized starch cross 80 meshes respectively；Povidone is configured to 5% povidone solution, it is spare as adhesive；It will sieving
Material be added in wet granulator 5min mixed with 200 revs/min of speed, add binder solution softwood, 16 mesh
Sieve granulation, 32 DEG C of dry 50min, 18 mesh sieves；
(2) by the dextrorotation Oxiracetam particle of preparation, it tabletting: is put into rotation after mixing with magnesium stearate and xylitol
It is tabletted in formula tablet press machine, turntable revolving speed 16r/min, stuffing pressure 36N, depth of fill 14mm.
Embodiment 6
Prescription: 70 parts, 30 parts microcrystalline celluloses of crystal form dextrorotation Oxiracetam of the preparation of embodiment 1,25 parts of low substitutions
Hydroxypropylcellulose, 8 parts of methylcellulose, 3 parts of superfine silica gel powders, 2 parts of glycyrrhizic acid monoammonium S.Preparation process
(1) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material and crystallite of crystal form
Cellulose, low-substituted hydroxypropyl cellulose cross 80 meshes respectively；Methylcellulose is configured to 5% methocel solution, is made
It is spare for adhesive；Screened material is added in wet granulator, 8min is mixed with 100 revs/min of speed, added viscous
Mixture solution softwood, the granulation of 16 meshes, 20 DEG C of dry 70min, 18 mesh sieves；
(2) tabletting: the dextrorotation Oxiracetam particle of preparation is put after mixing with superfine silica gel powder and glycyrrhizic acid monoammonium S
Enter tabletted in rotary tablet machine, turntable revolving speed 15r/min, stuffing pressure 30N, depth of fill 10mm.
Embodiment 7
Prescription: 125 parts, 5 parts starch of dextrorotation Oxiracetam of crystal form prepared by embodiment 1,10 parts of crospovidone,
3 parts of hydroxypropyl celluloses, 1 part of magnesium stearate, 1 part of aspartame.
Preparation process
(1) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material of crystal form and shallow lake
Powder, crospovidone cross 80 meshes respectively；Hydroxypropyl cellulose is configured to 10% hydroxypropyl cellulose solution, as bonding
Agent is spare；Screened material is added in wet granulator, 3min is mixed with 350 revs/min of speed, it is molten to add adhesive
Liquid softwood, the granulation of 16 meshes, 40 DEG C of dry 40min, 18 mesh sieves；
(2) by the dextrorotation Oxiracetam particle of preparation, it tabletting: is put into rotation after mixing with magnesium stearate and aspartame
It is tabletted in rotatable tablet press machine, turntable revolving speed 30r/min, stuffing pressure 40N, depth of fill 20mm.
During embodiment 4-7 wet granule compression tablet, dextrorotation Oxiracetam and auxiliary material are not sticked substantially in granulation pot inner wall
On tablet press machine, preparation process is easy to operate.
Embodiment 8
Take this product according to dissolution method (two the first methods of annex XC of Chinese Pharmacopoeia version in 2015), water is solvent, dissolution
Liquid accumulates 500mL, 75 turns per minute of revolving speed, operates according to methods and took solution to filter in right amount at 5/8/15/30 minute respectively, and injection is efficient
Dissolution curve is measured in liquid phase.The performance indicators such as dextrorotation Oxiracetam Dissolution of Tablet of the present invention, which investigate result, see the table below 1.
The performance indicators such as the dextrorotation Oxiracetam Dissolution of Tablet of the present invention of table 1 are investigated
| Embodiment 4 | Embodiment 5 | Embodiment 6 | Embodiment 7 | |
| 5 minutes | 37.2% | 35.6% | 34.1% | 36.0% |
| 8 minutes | 69.8% | 67.0% | 65.4% | 66.7% |
| 15 minutes | 90.2% | 87.9% | 85.6% | 86.8% |
| 30 minutes | 99.9% | 99.7% | 99.8% | 99.6% |
| Appearance | It is unilateral smooth | It is unilateral smooth | It is unilateral smooth | It is unilateral smooth |
| Hardness | 9.90kg | 9.17kg | 9.42kg | 8.68kg |
| Fragile degree | 0.40% | 0.42% | 0.48% | 0.47% |
Dextrorotation Oxiracetam tablet prepared by the present invention is unilateral smooth, and hardness is suitble to long-distance fortune between 8.50-9.90kg
It is defeated, while dissolution rate is fast, 30min is dissolved out completely substantially, and friability is lower than 0.5%.
Claims (8)
1. a kind of preparation method of dextrorotation Oxiracetam tablet, 70~125 weight are contained in the dextrorotation Oxiracetam tablet of preparation
Part crystal form dextrorotation Oxiracetam, 5~30 parts by weight of filler, 5-25 part by weight of disintegrant, 3-10 parts by weight of binder,
1-3 parts by weight lubricant, 1-3 parts by weight corrigent；The dextrorotation Oxiracetam of the crystal form is radiated using Cu-K α, is obtained
The X- ray powder diffraction arrived is composed in 2 θ of angle of reflectionFor14.14±0.2°、17.76±0.2°、18.72±0.2°、20.16±
0.2 °, 21.20 ± 0.2 °, 21.52 ± 0.2 °, 24.17 ± 0.2 °, 25.88 ± 0.2 ° has diffraction maximum；Preparation process includes standby
Material, wet granulation and tableting step, it is characterised in that: the stock is to weigh each supplementary material by recipe quantity, wherein crystal form
Dextrorotation Oxiracetam raw material and filler, disintegrating agent respectively cross 80 meshes；The adhesive that adhesive is configured to 3-15% is molten
Liquid, it is spare as adhesive；The wet granulation is that screened material is added in wet granulator with 100-350 revs/min
Speed mix 3-8min, add binder solution softwood, the granulation of 16 meshes, 20-40 DEG C of dry 40-70min, 18 meshes
Whole grain；The tabletting is the dextrorotation Oxiracetam particle that will be prepared, and is put into after mixing rotatably with lubricant and corrigent
Tabletted in tablet press machine, turntable 15~30r/min of revolving speed, stuffing pressure is 30~40N, and depth of fill is 10~20mm.
2. the method as described in claim 1, it is characterised in that: in the dextrorotation Oxiracetam tablet of the preparation containing 85~
The crystal form dextrorotation Oxiracetam of 110 parts by weight, 10~30 parts by weight of filler, 8-20 part by weight of disintegrant, 5-10 weight
Part adhesive, 1-3 parts by weight lubricant, 1-2 parts by weight corrigent.
3. method according to claim 1 or 2, it is characterised in that: the filler be selected from calcium monohydrogen phosphate, dextrin, lactose,
Mannitol, aluminium hydroxide, magnesium carbonate, microcrystalline cellulose, fructose, sorbierite, sucrose, starch and combinations thereof；The disintegrating agent choosing
Self-crosslinking sodium carboxymethylcellulose, crospovidone, Sodium Hydroxymethyl Stalcs, low-substituted hydroxypropyl cellulose, pregelatinized starch or
A combination thereof；Adhesive is selected from hydroxypropyl cellulose, hypromellose, copolyvidone, povidone, starch slurry, Methyl cellulose
Element or combinations thereof；The lubricant is selected from magnesium stearate, superfine silica gel powder, talcum powder, hydrogenated vegetable oil or combinations thereof；The flavoring
Agent is selected from aspartame, xylitol, Sucralose, glycyrrhizic acid monoammonium S or combinations thereof.
4. method as claimed in claim 3, it is characterised in that: the filler is selected from dextrin, mannitol, microcrystalline cellulose
Element, sorbierite, starch and combinations thereof.
5. method as claimed in claim 3, it is characterised in that: the disintegrating agent is selected from croscarmellose sodium, hands over
Join povidone, low-substituted hydroxypropyl cellulose.
6. method according to claim 1 or 2, it is characterised in that: the dextrorotation Oxiracetam of the crystal form is using such as
Lower step is made: dextrorotation Oxiracetam being dissolved in the hydrochloric acid that mass concentration is >=30%, the weight of hydrochloric acid and dextrorotation Oxiracetam
Amount is stirred continuously than being 1~3:1, is warming up to 50~80 DEG C of 1~5h of heat preservation, with adjusting PH with base value to 7~8, it is de- that active carbon is added
Color, filtering, filtrate is moved in crystallizer, stream plus the acetonitrile of hydrochloric acid volume 1/3~1/2 into crystallizer, 1~3 h of growing the grain, so
It afterwards with adjusting PH with base value to 7~8, filters, filter residue is at 30~40 DEG C, relative humidity dry 3-8h under conditions of being 60-90%, i.e.,
?；The alkali is the sodium hydrate aqueous solution or potassium hydroxide aqueous solution that mass concentration is 10~20%.
7. method as claimed in claim 6, it is characterised in that: the dextrorotation Oxiracetam of the crystal form is using following step
Rapid to be made: it is in >=30% hydrochloric acid that dextrorotation Oxiracetam, which is dissolved in mass concentration, and the weight ratio of hydrochloric acid and dextrorotation Oxiracetam is 1
~3:1, is stirred continuously, and mixing speed is 150r/min~350r/min, is warming up to 60~80 DEG C of 1~3h of heat preservation, uses adjusting PH with base
To 7~8 activity carbon decoloring is added, filtering moves to filtrate in crystallizer, and stream plus acetonitrile into crystallizer, stream add acetonitrile in value
Volume is the 1/3~1/2 of hydrochloric acid volume, and flow acceleration is 4~7mL/min, later 1~3 h of growing the grain, is then with mass concentration
10~20% sodium hydrate aqueous solution tune pH value filters, for filter residue at 30~40 DEG C, relative humidity is the item of 60-90% to 7~8
Under part dry 3-5h to get.
8. a kind of preparation method of dextrorotation Oxiracetam tablet, using following steps:
(1) preparation of the dextrorotation Oxiracetam of crystal form: by dextrorotation Oxiracetam be dissolved in mass concentration be >=30% hydrochloric acid in,
The weight ratio of hydrochloric acid and dextrorotation Oxiracetam is 1~3:1, is stirred continuously, and mixing speed is 150r/min~350r/min, heating
Active carbon decoloring is added with adjusting PH with base value to 7~8 to 60~80 DEG C of 1~3h of heat preservation, filtering moves to filtrate in crystallizer,
The volume of stream plus acetonitrile into crystallizer, stream plus acetonitrile is the 1/3~1/2 of hydrochloric acid volume, and flow acceleration is 4~7mL/min, it
1~3 h of growing the grain afterwards, the sodium hydrate aqueous solution tune pH value for being then 10~20% with mass concentration filter, filter residue exists to 7~8
30~40 DEG C, relative humidity is 3-5h dry under conditions of 60-90% to get the dextrorotation Oxiracetam of crystal form；
(2) wet granulation: weighing each supplementary material by recipe quantity, wherein the dextrorotation Oxiracetam raw material of crystal form and filler,
Disintegrating agent crosses 80 meshes respectively；Adhesive is configured to the binder solution of 3-15%, it is spare as adhesive；By the object of sieving
Material, which is added in wet granulator, mixes 3-8min with 100-350 revs/min of speed, adds binder solution softwood, and 16
Mesh granulation, 20-40 DEG C of dry 40-70min, 18 mesh sieves；
(3) by the dextrorotation Oxiracetam particle of preparation, it tabletting: is put into rotary tabletting after mixing with lubricant and corrigent
Tabletted in machine, turntable 15~30r/min of revolving speed, stuffing pressure is 30~40N, and depth of fill is 10~20mm.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810365769 | 2018-04-23 | ||
| CN2018103657691 | 2018-04-23 |
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| CN110384666A true CN110384666A (en) | 2019-10-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201811308085.4A Withdrawn CN110384666A (en) | 2018-04-23 | 2018-11-05 | A kind of method of wet granule compression tablet preparation dextrorotation Oxiracetam tablet |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112022816A (en) * | 2020-07-31 | 2020-12-04 | 河北君临药业有限公司 | Piracetam tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| CN102603607A (en) * | 2011-01-21 | 2012-07-25 | 重庆润泽医疗器械有限公司 | Preparation method of (R)-oxiracetam |
-
2018
- 2018-11-05 CN CN201811308085.4A patent/CN110384666A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| CN102603607A (en) * | 2011-01-21 | 2012-07-25 | 重庆润泽医疗器械有限公司 | Preparation method of (R)-oxiracetam |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112022816A (en) * | 2020-07-31 | 2020-12-04 | 河北君临药业有限公司 | Piracetam tablet and preparation method thereof |
| CN112022816B (en) * | 2020-07-31 | 2022-08-12 | 河北君临药业有限公司 | Piracetam tablet and preparation method thereof |
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Application publication date: 20191029 |