CN106890157A - It is a kind of to be difficult levo-oxiracetam effervescent tablet of moisture absorption and preparation method thereof - Google Patents
It is a kind of to be difficult levo-oxiracetam effervescent tablet of moisture absorption and preparation method thereof Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- 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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- 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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Abstract
A kind of levo-oxiracetam effervescent tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 3 ~ 6 parts of tartaric acid, 3 ~ 6 parts of sodium acid carbonate, 0.5 ~ 0.9 part of sodium chloride, 0.75 ~ 1.35 part of Macrogol 6000,0.2 ~ 0.8 part of Macrogol 4000,1 ~ 5 part of dextrin, 3 ~ 8 parts of sucrose, volume fraction are 15 ~ 25 parts of 50% ~ 70% ethanol solution, 3 ~ 9 parts of sodium carboxymethylcellulose, 7 ~ 13 parts of microcrystalline cellulose；It is good according to mobility of particle in levo-oxiracetam effervescent tablet preparation process obtained in the present invention, not sub- angle is less than 35 °, and tablet weight variation is less than 3%, and tableting processes will not sticking, finished product aerogenesis is fast, disintegration rate is fast, and disintegration time limited is no more than 30 seconds, and product storage process is difficult moisture absorption and goes bad, it is easy to preserve, shelf life is 30 months, and preparation process is simple is feasible, is worth marketing.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of levo-oxiracetam effervescent tablet and preparation method thereof.
Background technology
Oxiracetam (S-oxiracetam) is a kind of hydroxy-amino-butyric acid of synthesis (BABOB) cyclic derivatives, only
For central nervous system, cerebral cortex, hippocampus are mainly distributed on, have activation, protection or promote the function of nerve cell
Recover, improve the mnemonic learning function of disturbance of intelligence patient, and medicine in itself without direct vasoactive, also without in
Pivot excitation, the influence to ability of learning and memory is a kind of lasting facilitation.
The medicine was listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Parenteral solution,
5ml∶1g.It is domestic at present there was only oxiracetam capsule and parenteral solution listing, and main active used is racemic modification.
The rush that Ye Lei etc. goes into a coma caused by mentioning levo-oxiracetam in the A patents of Publication No. CN 103735545 to alcoholism
Effect of waking up is obvious, and dextrorotation Oxiracetam is not acted on substantially, and the above-mentioned rush of levo-oxiracetam wakes up effect for racemization Aura
Western smooth 2 times；Levo-oxiracetam is notable to the promoting wakening of stupor caused by wound, anesthesia.Peak etc. is opened in Publication No.
Levo-oxiracetam is disclosed in the patent of the A of CN 103599101 to traumatic brain injury rat caused by hydraulic pressure and freely falling body
Learning and memory cognition dysfunction improves significantly, and its drug effect is far above dextrorotation Oxiracetam.And 200mg/kg
Levo-oxiracetam is suitable with the effect of 400mg/kg Oxiracetams.Pharmacokinetic study results show：Left-handed Aura
Western smooth and dextrorotation Oxiracetam is in beasle dog body without obvious chiral inversion.Beasle dog single intravenous injection gives left-handed and 2
After the racemization Oxiracetam of multiple dose in blood plasma levo-oxiracetam the equal no significant difference of main pharmacokinetic parameters.Safe medicine
The result of the tests such as reason, anxious poison malicious, long show that under isodose level, levo-oxiracetam is with Oxiracetam to tested
Animal or the toxicity no significant difference of cell.Above-mentioned preclinical result of study shows that levo-oxiracetam is Oxiracetam
The main active of drug effect is played in vivo, this product is used alone can reduce Clinical practice dosage, reduce potential poison secondary anti-
Should.
It is poor that existing Oxiracetam effervescent formulation is primarily present production process mobility of particle, the easy sticking of tableting processes, compressing tablet
The tablet weight variation of obtained sheet is big, finished product aerogenesis is slow, disintegration is slow, and easily moisture absorption is gone bad during product storage, and stability is poor,
The technical problem such as shelf life is short.
The content of the invention
The rotten levo-oxiracetam effervescent tablet of moisture absorption is difficult it is an object of the invention to provide a kind of storage process.
Preparation method another object of the present invention is to provide above-mentioned levo-oxiracetam effervescent tablet.
The purpose of the present invention is realized by following technical measures：
A kind of aerogenesis is fast, be disintegrated fast levo-oxiracetam effervescent tablet, it is characterised in that it is to be with levo-oxiracetam
Raw material, adds a certain amount of acid source, alkali source, adhesive, lubricant, filler, flavouring and is obtained；It is wherein described
Acid source is the one kind in citric acid, tartaric acid, fumaric acid, adipic acid, malic acid；The alkali source is sodium carbonate, carbonic acid
One kind in hydrogen sodium, potassium carbonate, saleratus, calcium carbonate；Described adhesive is water, ethanol, sucrose, starch slurry, paste
One or more in essence, copolyvidone VA64 (PVP/VA64)；The lubricant is talcum powder, magnesium stearate, poly- second
Glycol 4000, Macrogol 6000, stearic acid, calcium stearate, lauryl sodium sulfate, superfine silica gel powder, magnesia, paraffin
In one or more；Filler be starch, lactose, dextrin, Icing Sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose,
One or more in glucose, sodium carboxymethylcellulose, sodium chloride；The flavouring is sucrose, maltose, ethyl malt
Phenol, Sucralose, stevia rebaudianum are sweet, one or more in sorbierite, mannitol, glucose, aspartame, essence.
Inventor has found that selection suitable supplementary product kind, specific supplementary material consumption proportion relation are matched somebody with somebody in research process
Special processing method is closed, can cause that above-mentioned levo-oxiracetam effervescent tablet production process mobility of particle is good, compressing tablet piece
Stablize again, tableting processes will not sticking, finished product aerogenesis is fast, and disintegration is fast, finished product storage process will not the moisture absorption go bad；It is above-mentioned
Levo-oxiracetam effervescent tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：Levo-oxiracetam
1 part, 3~6 parts of tartaric acid, 3~6 parts of sodium acid carbonate, 0.5~0.9 part of sodium chloride, 0.75~1.35 part of Macrogol 6000,
0.2~0.8 part of Macrogol 4000,1~5 part of dextrin, 3~8 parts of sucrose, volume fraction are 50%~70% ethanol solution
15~25 parts, 3~9 parts of sodium carboxymethylcellulose, 7~13 parts of microcrystalline cellulose；Take recipe quantity levo-oxiracetam,
Tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, microcrystalline cellulose mixing, are placed in Universalpulverizer, crush,
Mixed-powder is collected after crossing 100 mesh sieves, mixed-powder is placed in adhesive is added in wet granulator, start granulator (peace
Fill 18 mesh nylon mesh), granulation obtains sour phase particle, standby；Sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in
Crushed in Universalpulverizer, mixed-powder is collected after crossing 100 mesh sieves, it is standby；By the Macrogol 6000 of recipe quantity, gather
The heating fusing of ethylene glycol 4000, sets 40~45 DEG C of fusion temperature, treats Macrogol 6000 and Macrogol 4000 fusing
Afterwards, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, is uniformly mixed, be placed in Universalpulverizer after cooling,
Crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator, start granulator (installing 18 mesh nylon mesh),
Granulation, obtains alkali phase particle, standby.
Further, in order to improve mobility of particle in levo-oxiracetam effervescent tablet tableting processes, disintegration time is accelerated,
A kind of levo-oxiracetam effervescent tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：Left-handed Aura
Western smooth 1 part, 3~5 parts of tartaric acid, 3~5 parts of sodium acid carbonate, 0.7~0.9 part of sodium chloride, Macrogol 6000 1.05~1.35
Part (sodium chloride: Macrogol 6000=2: 3), 0.4~0.7 part of Macrogol 4000,3~5 parts of dextrin, sucrose 5~7
Part, volume fraction are 18~23 parts of 50%~70% ethanol solution, 5~8 parts of sodium carboxymethylcellulose, microcrystalline cellulose 9~12
Part；The levo-oxiracetam of recipe quantity, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, microcrystalline cellulose is taken to mix
Close, be placed in Universalpulverizer, crush, mixed-powder is collected after crossing 100 mesh sieves, mixed-powder is placed in wet granulation
Adhesive is added in machine, starts granulator (installing 18 mesh nylon mesh), granulation obtains sour phase particle, standby；Take prescription
The sodium acid carbonate of amount, sodium chloride mixing, are placed in Universalpulverizer and crush, and mixed-powder is collected after crossing 100 mesh sieves, standby
With；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing, 42 DEG C of fusion temperature is set, treat poly- second
After glycol 6000 and Macrogol 4000 fusing, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride, stirring mixing are added
Uniformly, it is placed in Universalpulverizer after cooling, is crushed, is placed in after 100 mesh sieves excessively and adhesive is added in wet granulator,
Start granulator (installing 18 mesh nylon mesh), granulation obtains alkali phase particle, standby.
Supplementary material needed for above-mentioned, is well known to those skilled in the art, and in the market is commercially available.
A kind of preparation method of the levo-oxiracetam effervescent tablet for being difficult moisture absorption, it is characterised in that it is to make as follows
：
1. levo-oxiracetam, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, the microcrystalline cellulose of recipe quantity are taken
Mixing, is placed in Universalpulverizer, crushes, and mixed-powder is collected after crossing 100 mesh sieves, and mixed-powder is placed in into wet method system
Adhesive is added in grain machine, starts granulator (installing 18 mesh nylon mesh), granulation obtains sour phase particle, standby；
2. Macrogol 6000, the Macrogol 4000 heating fusing of recipe quantity are taken, 42 DEG C of fusion temperature is set, waits to gather
After ethylene glycol 6000 and Macrogol 4000 fusing, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, stirring is mixed
Close uniform, be placed in Universalpulverizer after cooling, crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator,
Start granulator (installing 18 mesh nylon mesh), granulation obtains alkali phase particle, standby；
3. in sour phase wet granular, alkali phase wet granular being put into air dry oven respectively, 40 DEG C~50 DEG C of design temperature, control
Relative humidity is less than 30%, starts drying；Particle situation is observed at any time, and drying time is 120~150 minutes, it is ensured that
Grain moisture≤2%；
4. whole grain, sub-sieve：Sour phase particle is mixed with alkali phase particle and is placed in crushing and pelletizing machine, with 24 mesh sieve whole grains,
Below 25 DEG C of environment temperature of control, relative humidity is below 30%；
5. compressing tablet：Tablet press machine pressure, adjustment sheet weight are set, compressing tablet is controlled below 25 DEG C of environment temperature, relative humidity
Less than 30%；
6. bag in：Packed with Aluminium-coating Packer with levo-oxiracetam effervescent tablet, set packing specification as 6 sheet panels, controlled
Below 25 DEG C of environment temperature, below 30%, packaging is obtained final product relative humidity.
The present invention has following beneficial effect：
Mobility of particle is good in levo-oxiracetam effervescent tablet preparation process of the present invention, and not sub- angle is less than 35., tablet weight variation
Less than 3%, tableting processes will not sticking, finished product aerogenesis is fast, and disintegration rate is fast, and disintegration time limited is no more than 30 seconds, product
Storage process is difficult moisture absorption and goes bad, it is easy to preserve, shelf life is 30 months, and preparation process is simple is feasible, is worth
Marketing.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be that following examples are served only for
The present invention is further described, it is impossible to be interpreted as limiting the scope of the invention, without departing substantially from spirit of the invention
In the case of essence, the modification or replacement made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of levo-oxiracetam effervescent tablet for being difficult the moisture absorption, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Tartaric acid | 3 parts |
| Sodium acid carbonate | 3 parts |
| Sodium chloride | 0.7 part |
| Macrogol 6000 | 1.05 parts |
| Macrogol 4000 | 0.4 part |
| Dextrin | 3 parts |
| Sucrose | 5 parts |
| Volume fraction is 50% ethanol solution | 18 parts |
| Sodium carboxymethylcellulose | 5 parts |
| Microcrystalline cellulose | 9 parts |
It is made 1000
Preparation process：
1. levo-oxiracetam, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, the microcrystalline cellulose of recipe quantity are taken
Mixing, is placed in Universalpulverizer, crushes, and mixed-powder is collected after crossing 100 mesh sieves, and mixed-powder is placed in into wet method system
Adhesive is added in grain machine, starts granulator (installing 18 mesh nylon mesh), granulation obtains sour phase particle, standby；
2. Macrogol 6000, the Macrogol 4000 heating fusing of recipe quantity are taken, 42 DEG C of fusion temperature is set, waits to gather
After ethylene glycol 6000 and Macrogol 4000 fusing, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, stirring is mixed
Close uniform, be placed in Universalpulverizer after cooling, crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator,
Start granulator (installing 18 mesh nylon mesh), granulation obtains alkali phase particle, standby；
3. in sour phase wet granular, alkali phase wet granular being put into air dry oven respectively, 40 DEG C~50 DEG C of design temperature, control
Relative humidity is less than 30%, starts drying；Particle situation is observed at any time, and drying time is 120~150 minutes, it is ensured that
Grain moisture≤2%；
4. whole grain, sub-sieve：Sour phase particle is mixed with alkali phase particle and is placed in crushing and pelletizing machine, with 24 mesh sieve whole grains,
Below 25 DEG C of environment temperature of control, relative humidity is below 30%；
5. compressing tablet：Tablet press machine pressure, adjustment sheet weight are set, compressing tablet is controlled below 25 DEG C of environment temperature, relative humidity
Less than 30%；
6. bag in：Packed with Aluminium-coating Packer with levo-oxiracetam effervescent tablet, set packing specification as 6 sheet panels, controlled
Below 25 DEG C of environment temperature, below 30%, packaging is obtained final product relative humidity.
Experiment one：Particle is stopped sub- angle and is determined
1. test material：Gained sample after whole grain in the preparation process of embodiment 1
2. test method：After the completion of the whole grain of embodiment 1, taken respectively in the upper, middle and lower of particle, left and right each point respectively
Sample determines angle of repose, judges its mobility；
3. result of the test：
4. conclusion (of pressure testing)：Be can be seen that by upper table result of the test, five times measurement angle of repose is respectively less than 33 °, shows particle flow
Property is good.
Experiment two：Tablet weight variation
1. test material：10, effervescent tablet sample obtained in Example 1, shine《Chinese Pharmacopoeia》Version two in 2010
The lower tablet weight variation inspection of annex tablet.
2. determination method：Test sample 10 is taken, weighed per sheet weight respectively, the weight of every compares with average piece heavy phase.
3. result of the test：Tablet weight variation inspection result see the table below：
4. conclusion (of pressure testing)：This product tablet weight variation can be seen that by upper table result of the test and be respectively less than ± 3%, it was demonstrated that tablet weight variation is small.
Experiment three：The levo-oxiracetam Effervescent tablet disintegration time limit
1. test material：10, effervescent tablet sample obtained in Example 1, check disintegration time limited.
2. determination method：Test sample 10 is taken, is respectively placed in conical flask, add purified water 50ml, record effervescent tablet to collapse
Solution required time completely.
3. result of the test：Disintegration time limited inspection result see the table below：
| Sample number into spectrum | 1# | 2# | 3# | 4# | 5# |
| Disintegration time (s) | 23 | 25 | 22 | 24 | 19 |
| Sample number into spectrum | 6# | 7# | 8# | 9# | 10# |
| Disintegration time | 25 | 23 | 25 | 27 | 24 |
4. conclusion (of pressure testing)：From upper table result of the test, the levo-oxiracetam Effervescent tablet disintegration time is respectively less than 30s.
Experiment four：Finished product moisture absorption weightening is determined
1. test material：Embodiment 1 is obtained sample
2. test method：10, sample obtained in Example 1 is respectively placed in relative humidity 75% after being packed by commercially available product
Placed 10 days with the environment of relative humidity 92.5%, weighed in sampling in 5 days and 10 days, determine its moisture absorption weightening
Rate, investigates the situation of moisture absorption weightening.
3. result of the test：
4. conclusion (of pressure testing)：Be can be seen that by upper table result of the test, the prepared sample of the present invention is respectively placed in the He of relative humidity 75%
In 92.5% environment, place 10 days moisture absorption rates of body weight gain and be respectively 1.3% and 1.5%, thus product moisture absorption weightening compared with
It is small, it is easy to preserve.
Experiment five：Levo-oxiracetam effervescent tablet stability experiment
Experiment material：
Levo-oxiracetam effervescent tablet：For embodiment 1 is obtained.
Acceleration study method：Levo-oxiracetam effervescent tablet obtained in embodiment 1 is packed by listing, Acceleration study case is put
In, certain hour sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Acceleration study humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：Proterties, tablet weight variation, disintegration time limited, relevant material, content, microbial limit
Accelerated test stability is recorded：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
Speed experiment June, quality keeps stabilization, and this product stability is preferable.
Long-term experiment method：Levo-oxiracetam effervescent tablet obtained in embodiment 1 is packed by listing, the long-term case that keeps sample is put
In, certain hour sampling is tested to investigation project.
Long-term experiment temperature：25±2℃
Long-term experiment humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24,30 months
Inspection target：Proterties, tablet weight variation, disintegration time limited, relevant material, content, microbial limit
Long term test stability is recorded：
Long term test shows：30 months proterties of this product long term test, tablet weight variation, disintegration time limited, relevant material, contain
Amount, microbial limit without significant changes, meet every relevant regulations of production quality standard draft.This product is long-term
30 months steady qualities of experiment, therefore minimum 30 months of this product term of validity, long term test is still during continuing to investigate.
Embodiment 2
A kind of levo-oxiracetam effervescent tablet for being difficult moisture absorption, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Tartaric acid | 5 parts |
| Sodium acid carbonate | 5 parts |
| Sodium chloride | 0.9 part |
| Macrogol 6000 | 1.35 parts |
| Macrogol 4000 | 0.7 part |
| Dextrin | 5 parts |
| Sucrose | 7 parts |
| Volume fraction is 70% ethanol solution | 23 parts |
| Sodium carboxymethylcellulose | 8 parts |
| Microcrystalline cellulose | 12 parts |
It is made 1000
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, particle is carried out respectively and is stopped
Sub- angle measure, tablet weight variation inspection, disintegration time limited inspection, moisture absorption weightening are determined and sample stability experiment, not sub- angle
Experiment measurement result shows that this product mobility of particle is good, and particle stops sub- angle less than 35 °, and tablet weight variation experiment shows this product piece
The method of double differences is different to be less than 2%, and disintegration time limited inspection result shows that this product disintegration time is respectively less than 30 seconds, and relative humidity 75% is placed
Product moisture absorption rate of body weight gain is 1.2% within 10 days, and it is 1.5% that relative humidity 92.5% places 10 days product moisture absorption rates of body weight gain, is shown
Finished product is difficult moisture absorption, and stability test result shows to accelerate June sample quality stable, long-term 30 months steady qualities,
Therefore this product term of validity at least 30 months.
Embodiment 3
A kind of levo-oxiracetam effervescent tablet for being difficult moisture absorption, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Tartaric acid | 4 parts |
| Sodium acid carbonate | 4 parts |
| Sodium chloride | 0.8 part |
| Macrogol 6000 | 1.2 parts |
| Macrogol 4000 | 0.5 part |
| Dextrin | 4 parts |
| Sucrose | 6 parts |
| Volume fraction is 60% ethanol solution | 21 parts |
| Sodium carboxymethylcellulose | 7 parts |
| Microcrystalline cellulose | 10 parts |
It is made 1000
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, particle is carried out respectively and is stopped
Sub- angle measure, tablet weight variation inspection, disintegration time limited inspection, moisture absorption weightening are determined and sample stability experiment, not sub- angle
Experiment measurement result shows that this product mobility of particle is good, and particle stops sub- angle less than 35 °, and tablet weight variation experiment shows this product piece
The method of double differences is different to be less than 3%, and disintegration time limited inspection result shows that this product disintegration time is respectively less than 30 seconds, and relative humidity 75% is placed
Product moisture absorption rate of body weight gain is 1.1% within 10 days, and it is 1.6% that relative humidity 92.5% places 10 days product moisture absorption rates of body weight gain, is shown
Finished product is difficult moisture absorption, and stability test result shows to accelerate June sample quality stable, long-term 30 months steady qualities,
Therefore this product term of validity at least 30 months.
Embodiment 4-6：A kind of levo-oxiracetam effervescent tablet, is prepared, preparation method by the supplementary material of following weight
With embodiment 1：
| Embodiment | 4 | 5 | 6 |
| Levo-oxiracetam | 1 part | 1 part | 1 part |
| Tartaric acid | 3 parts | 4 parts | 5 parts |
| Sodium acid carbonate | 3 parts | 4 parts | 5 parts |
| Sodium chloride | 0.9 part | 0.8 part | 0.7 part |
| Macrogol 6000 | 1.35 parts | 1.2 parts | 1.05 parts |
| Macrogol 4000 | 0.5 part | 0.6 part | 0.6 part |
| Dextrin | 5 parts | 4 parts | 3 parts |
| Sucrose | 7 parts | 6 parts | 5 parts |
| Volume fraction is 60% ethanol solution | 20 parts | 21 parts | 20 parts |
| Sodium carboxymethylcellulose | 7 parts | 6 parts | 7 parts |
| Microcrystalline cellulose | 10 parts | 11 parts | 12 parts |
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, by embodiment 4,5,
Sample obtained by 6 carries out particle and stops sub- angle measure, tablet weight variation inspection, disintegration time limited inspection, moisture absorption weightening survey respectively
Fixed and sample stability experiment, embodiment 4,5,6 is stopped sub- angle experiment measurement result and shows that this product mobility of particle is good,
Particle is stopped sub- angle and is below 35 °, and the experiment of the tablet weight variation of embodiment 4,5,6 shows that this product tablet weight variation is respectively less than 2%,
The disintegration time limited inspection result of embodiment 4,5,6 shows that this product disintegration time is respectively less than 30 seconds, the sample of embodiment 4,5,6
Product place 10 days product moisture absorption rates of body weight gain and are respectively 1.1%, 1.1%, 1.0% in relative humidity 75%, embodiment 4,5,
6 samples place 10 days product moisture absorption rates of body weight gain and are respectively 1.5%, 1.4%, 1.5% in relative humidity 92.5%, show into
Product are difficult moisture absorption, and the stability test result of embodiment 4,5,6 shows to accelerate June sample quality stabilization, long-term 30
Month steady quality, therefore this product term of validity at least 30 months.
Claims (3)
1. a kind of levo-oxiracetam effervescent tablet for being difficult moisture absorption, it is characterised in that it is obtained by the supplementary material of following weight proportion：About 1 part of levo-oxiracetam, about 3 ~ 6 parts of tartaric acid, about 3 ~ 6 parts of sodium acid carbonate, about 0.5 ~ 0.9 part of sodium chloride, about 0.75 ~ 1.35 part of Macrogol 6000, about 0.2 ~ 0.8 part of Macrogol 4000, about 1 ~ 5 part of dextrin, about 3 ~ 8 parts of sucrose, volume fraction are about 15 ~ 25 parts of 50% ~ 70% ethanol solution, about 3 ~ 9 parts of sodium carboxymethylcellulose, about 7 ~ 13 parts of microcrystalline cellulose；Take levo-oxiracetam, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, the microcrystalline cellulose mixing of recipe quantity; it is placed in Universalpulverizer, crushes, mixed-powder is collected after crossing 100 mesh sieves; mixed-powder is placed in adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains sour phase particle, standby；Sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in Universalpulverizer and is crushed, mixed-powder is collected after crossing 100 mesh sieves, it is standby；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing; 40 ~ 45 DEG C of fusion temperature of setting; after after Macrogol 6000 and Macrogol 4000 fusing; add the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride; it is uniformly mixed, is placed in Universalpulverizer after cooling, crushes; cross after 100 mesh sieves to be placed in and adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains alkali phase particle, standby.
2. levo-oxiracetam effervescent tablet as claimed in claim 1, it is characterised in that it is obtained by the supplementary material of following weight proportion：About 1 part of levo-oxiracetam, about 3 ~ 5 parts of tartaric acid, about 3 ~ 5 parts of sodium acid carbonate, about 0.7 ~ 0.9 part of sodium chloride, about 1.05 ~ 1.35 parts of Macrogol 6000（Sodium chloride：Macrogol 6000=2:3）, about 0.4 ~ 0.7 part of Macrogol 4000, about 3 ~ 5 parts of dextrin, about 5 ~ 7 parts of sucrose, volume fraction be about 18 ~ 23 parts of 50% ~ 70% ethanol solution, about 5 ~ 8 parts of sodium carboxymethylcellulose, about 9 ~ 12 parts of microcrystalline cellulose；Take levo-oxiracetam, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, the microcrystalline cellulose mixing of recipe quantity; it is placed in Universalpulverizer, crushes, mixed-powder is collected after crossing 100 mesh sieves; mixed-powder is placed in adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains sour phase particle, standby；Sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in Universalpulverizer and is crushed, mixed-powder is collected after crossing 100 mesh sieves, it is standby；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing; 42 DEG C of fusion temperature of setting; after after Macrogol 6000 and Macrogol 4000 fusing; add the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride; it is uniformly mixed, is placed in Universalpulverizer after cooling, crushes; cross after 100 mesh sieves to be placed in and adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains alkali phase particle, standby.
3. the preparation method of levo-oxiracetam effervescent tablet as claimed in claim 1 or 2, it is characterised in that it is obtained as follows：
A. levo-oxiracetam, tartaric acid, dextrin, sucrose, sodium carboxymethylcellulose, the microcrystalline cellulose mixing of recipe quantity are taken; it is placed in Universalpulverizer, crushes, mixed-powder is collected after crossing 100 mesh sieves; mixed-powder is placed in adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains sour phase particle, standby；
B. Macrogol 6000, the Macrogol 4000 heating fusing of recipe quantity are taken; 42 DEG C of fusion temperature of setting; after after Macrogol 6000 and Macrogol 4000 fusing; add the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride; it is uniformly mixed, is placed in Universalpulverizer after cooling, crushes; cross after 100 mesh sieves to be placed in and adhesive is added in wet granulator, start granulator（18 mesh nylon mesh are installed）, granulation obtains alkali phase particle, standby；
C. in sour phase wet granular, alkali phase wet granular being put into air dry oven respectively, 40 DEG C ~ 50 DEG C of design temperature, control relative humidity is less than 30%, starts drying；Particle situation is observed at any time, and drying time is 120 ~ 150 minutes, it is ensured that pellet moisture≤2%；
D. whole grain, sub-sieve:Sour phase particle is mixed with alkali phase particle and is placed in crushing and pelletizing machine, with 24 mesh sieve whole grains, below 25 DEG C of environment temperature of control, relative humidity is below 30%；
E. compressing tablet：Tablet press machine pressure, adjustment sheet weight are set, compressing tablet is controlled below 25 DEG C of environment temperature, and relative humidity is below 30%；
F. interior bag：Packed with Aluminium-coating Packer with levo-oxiracetam effervescent tablet, set packing specification as 6 sheet panels, below 25 DEG C of environment temperature of control, below 30%, packaging is obtained final product relative humidity.
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|---|---|---|---|---|
| US20060142182A1 (en) * | 2004-12-27 | 2006-06-29 | Miller Landon C | Piracetam and piracetam analog conjugate and a pharmaceutical composition for treatment of neuronal disorders |
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid preparation with levo-oxiracetam as active component |
| US20130059900A1 (en) * | 2010-05-21 | 2013-03-07 | Chao You | Crystal form i of (s)-4-hydroxy-2-oxo-1-pyrrolidine acetamide, preparing method and use thereof |
-
2015
- 2015-12-17 CN CN201510946329.1A patent/CN106890157A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060142182A1 (en) * | 2004-12-27 | 2006-06-29 | Miller Landon C | Piracetam and piracetam analog conjugate and a pharmaceutical composition for treatment of neuronal disorders |
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid preparation with levo-oxiracetam as active component |
| US20130059900A1 (en) * | 2010-05-21 | 2013-03-07 | Chao You | Crystal form i of (s)-4-hydroxy-2-oxo-1-pyrrolidine acetamide, preparing method and use thereof |
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