CN106902091A - A kind of delicious levo-oxiracetam effervescent tablet and preparation method thereof - Google Patents
A kind of delicious levo-oxiracetam effervescent tablet and preparation method thereof Download PDFInfo
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- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
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- 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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- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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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 delicious levo-oxiracetam effervescent tablet, it is obtained by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 5 ~ 9 parts of tartaric acid, 5 ~ 9 parts of sodium acid carbonate, 0.3 ~ 0.8 part of sodium chloride, 0.45 ~ 1.2 part of Macrogol 6000,0.8 ~ 1.3 part of Macrogol 4000,2 ~ 7 parts of dextrin, 0.3 ~ 0.8 part of Sucralose, 0.2 ~ 0.7 part of peppermint oil, 0.1 ~ 0.6 part of strawberry essence, volume fraction are 15 ~ 25 parts of 70% ~ 90% ethanol solution；It is good according to mobility of particle in levo-oxiracetam effervescent tablet preparation process obtained in the present invention, not sub- angle be less than 35 °, tableting processes will not sticking, tablet weight variation be less than 3%, finished product aerogenesis is fast, disintegration rate is fast, and disintegration time limited is no more than 30 seconds, delicious, easily received by most of patient, shelf life is up to 24 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 delicious levo-oxiracetam effervescent tablet and its system
Preparation Method.
Background technology
Oxiracetam was listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Note
Penetrate liquid, 1g/5ml.Domestic at present only have oxiracetam capsule and parenteral solution listing, and main active used be it is outer
Raceme.Caused by Ye Lei etc. mentions levo-oxiracetam to alcoholism in the A patents of Publication No. CN 103735545
The promoting wakening of stupor is obvious, and dextrorotation Oxiracetam is not acted on substantially, and the awake effect of above-mentioned rush of levo-oxiracetam is
2 times of racemization Oxiracetam；Levo-oxiracetam is notable to the promoting wakening of stupor caused by wound, anesthesia.Open peak etc.
It is traumatic caused by levo-oxiracetam is disclosed in the patent of the A of Publication No. CN 103599101 to hydraulic pressure and freely falling body
Brain injury in rats learning and memory cognition dysfunction improves significantly, and its drug effect is far above dextrorotation Oxiracetam.
And 200mg/kg levo-oxiracetams are suitable with the effect of 400mg/kg Oxiracetams.Pharmacokinetic study results show：
Levo-oxiracetam and dextrorotation Oxiracetam are in beasle dog body without obvious chiral inversion.Beasle dog single intravenous injection gives
The main pharmacokinetic parameters of levo-oxiracetam nothing is substantially poor in blood plasma after left-handed and 2 multiple doses racemization Oxiracetam
It is different.The result of the tests such as safe pharmacology, anxious poison malicious, long show, under isodose level, levo-oxiracetam and Aura
It is western smooth to animal subject or the toxicity no significant difference of cell.Above-mentioned preclinical result of study shows, levo-oxiracetam
It is the main active that drug effect is played in Oxiracetam body, this product is used alone can reduce Clinical practice dosage, reduces latent
Toxicity.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) chemical entitled 4- hydroxyls -2- OXo-1-pyrrolidine second
Acid amides, is that (compound is disclosed in the anti anoxia class cereboactive drug that synthesized first in 1974 of Italian ISFS.P.A companies
US4118396), it is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promotes brain metabolism,
Through blood-brain barrier, have stimulation to specific nervous centralis road, intelligence and memory can be improved, to cerebrovascular disease,
Brain trauma, brain tumor, intracranial infection, brain degenerative disease etc. also have preferable curative effect, and the drug toxicity is extremely low, nothing
Mutagenesis and carcinogenesis and genotoxicity.Giorgio et al. discloses the chemistry knot of Oxiracetam in US4118396
Structure and preparation method, Chiodini et al. are disclosed in WO9306826A, and clinical effectiveness proves S's configurations (left-handed)
The drug effect of Oxiracetam is better than R configurations (dextrorotation), and Oxiracetam and levo-oxiracetam structure are as follows.
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, taste is poor, is difficult the technology such as to receive by many patients
Problem.
The content of the invention
It is an object of the invention to provide a kind of delicious, levo-oxiracetam effervescent tablet that disintegration is fast.
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 delicious, levo-oxiracetam effervescent tablet that disintegration is fast, 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, sorbierite, mannitol, glucose, aspartame, peppermint oil, strawberry essence, apple fragrant
One or more in any of several broadleaf plants, peach flavor, chocolate 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 and product is delicious；Above-mentioned 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, tartaric acid
5~9 parts, 5~9 parts of sodium acid carbonate, 0.3~0.8 part of sodium chloride, 0.45~1.2 part of Macrogol 6000, Macrogol 4000
0.8~1.3 part, 2~7 parts of dextrin, 0.3~0.8 part of Sucralose, 0.2~0.7 part of peppermint oil, 0.1~0.6 part of strawberry essence,
Volume fraction is 15~25 parts of 70%~90% ethanol solution；The dextrin for taking recipe quantity is placed in and mills, and the quality such as adds
Purified water, mixing of milling adds the peppermint oil and strawberry essence of recipe quantity in operating process, continue to mill 10~20 minutes,
Take out, be placed in air dry oven, 40 DEG C~50 DEG C dryings of drying temperature to moisture is set and is taken out less than 3%, be placed in omnipotent
In pulverizer, levo-oxiracetam, tartaric acid, the Sucralose of recipe quantity, co-grinding, after crossing 100 mesh sieves are added
Mixed-powder is collected, mixed-powder is placed in adhesive is added in wet granulator, started granulator and (18 mesh Buddhist nuns are installed
Dragon sieve), granulation obtains sour phase particle, standby；Sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, omnipotent crushing is placed in
Crushed in machine, mixed-powder is collected after crossing 100 mesh sieves, it is standby；By the Macrogol 6000 of recipe quantity, polyethylene glycol
4000 heating fusings, set 40~45 DEG C of fusion temperature, after Macrogol 6000 and Macrogol 4000 melt, plus
Enter the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride, be uniformly mixed, be placed in Universalpulverizer after cooling, crush,
Cross after 100 mesh sieves to be placed in and adhesive is added in wet granulator, start granulator (installing 18 mesh nylon mesh), granulation,
Alkali phase particle is obtained, it is standby.
Further, in order to improve mobility of particle in levo-oxiracetam effervescent tablet tableting processes, disintegration time is accelerated,
So that finished product taste is more preferably, a kind of levo-oxiracetam effervescent tablet, it is characterised in that it is by the original of following weight proportion
Auxiliary material is obtained：1 part of levo-oxiracetam, 6~8 parts of tartaric acid, 6~8 parts of sodium acid carbonate, 0.5~0.7 part of sodium chloride,
0.75~1.05 part of Macrogol 6000 (sodium chloride: Macrogol 6000=2: 3), 0.9~1.1 part of Macrogol 4000,
3~5 parts of dextrin, 0.4~0.6 part of Sucralose, 0.3~0.5 part of peppermint oil, 0.2~0.5 part of strawberry essence, volume fraction
For 18~23 parts of 70%~90% ethanol solution；The dextrin for taking recipe quantity is placed in and mills, and the purified water of quality such as adds,
Mill mixing, the peppermint oil and strawberry essence of recipe quantity added in operating process, continue to mill 10~20 minutes, take out,
It is placed in air dry oven, 45 DEG C of dryings of drying temperature to moisture is set and is taken out less than 3%, is placed in Universalpulverizer,
Levo-oxiracetam, tartaric acid, the Sucralose of recipe quantity, co-grinding is added to collect mixed powder after crossing 100 mesh sieves
End, mixed-powder is placed in adhesive is added in wet granulator, starts granulator (installing 18 mesh nylon mesh), is pelletized,
Sour phase particle is obtained, it is standby；Sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in Universalpulverizer and is crushed, cross 100
Mixed-powder is collected after mesh sieve, it is standby；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing, if
Determine 42 DEG C of fusion temperature, after after Macrogol 6000 and Macrogol 4000 fusing, add above-mentioned sodium acid carbonate and chlorination
The mixed-powder of sodium, is uniformly mixed, and is placed in Universalpulverizer after cooling, crushes, and is placed in after 100 mesh sieves excessively wet
Adhesive is added in method granulator, starts 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 delicious levo-oxiracetam effervescent tablet, it is characterised in that it is prepared as follows
's：
1. the dextrin for taking recipe quantity is placed in and mills, and the purified water of quality, mixing of milling, addition in operating process such as adds
The peppermint oil and strawberry essence of recipe quantity, continue to mill 10~20 minutes, take out, and are placed in air dry oven, set dry
Dry temperature 45 C drying to moisture takes out less than 3%, is placed in Universalpulverizer, the levo-oxiracetam of addition recipe quantity,
Tartaric acid, Sucralose, co-grinding collect mixed-powder after crossing 100 mesh sieves, and mixed-powder is placed in into wet granulation
Adhesive is added in machine, starts granulator (installing 18 mesh nylon mesh), granulation obtains sour phase particle, standby；
2. sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in Universalpulverizer and is crushed, collected after crossing 100 mesh sieves
Mixed-powder, it is standby；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing, fusion temperature is set
42 DEG C, after after Macrogol 6000 and Macrogol 4000 fusing, add the mixed powder of above-mentioned sodium acid carbonate and sodium chloride
End, is uniformly mixed, and is placed in Universalpulverizer after cooling, crushes, and is placed in wet granulator after crossing 100 mesh sieves
Adhesive is added, starts 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 20 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 °, tableting processes
Will not sticking, tablet weight variation is less than 3%, and finished product aerogenesis is fast, and disintegration rate is fast, and disintegration time limited is no more than 30 seconds, taste
It is good, easily received by most of patient, shelf life is up to 24 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 delicious levo-oxiracetam effervescent tablet, is obtained according to the following steps：
Preparation process：
1. the dextrin for taking recipe quantity is placed in and mills, and the purified water of quality, mixing of milling, addition in operating process such as adds
The peppermint oil and strawberry essence of recipe quantity, continue to mill 10~20 minutes, take out, and are placed in air dry oven, set dry
Dry temperature 45 C drying to moisture takes out less than 3%, is placed in Universalpulverizer, the levo-oxiracetam of addition recipe quantity,
Tartaric acid, Sucralose, co-grinding collect mixed-powder after crossing 100 mesh sieves, and mixed-powder is placed in into wet granulation
Adhesive is added in machine, starts granulator (installing 18 mesh nylon mesh), granulation obtains sour phase particle, standby；
2. sodium acid carbonate, the sodium chloride mixing of recipe quantity are taken, is placed in Universalpulverizer and is crushed, collected after crossing 100 mesh sieves
Mixed-powder, it is standby；By the Macrogol 6000 of recipe quantity, Macrogol 4000 heating fusing, fusion temperature is set
42 DEG C, after after Macrogol 6000 and Macrogol 4000 fusing, add the mixed powder of above-mentioned sodium acid carbonate and sodium chloride
End, is uniformly mixed, and is placed in Universalpulverizer after cooling, crushes, and is placed in wet granulator after crossing 100 mesh sieves
Adhesive is added, starts 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 20 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：Disintegration time limited
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) | 26 | 23 | 27 | 23 | 25 |
| Sample number into spectrum | 6# | 7# | 8# | 9# | 10# |
| Disintegration time | 23 | 26 | 21 | 28 | 22 |
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：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 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：24 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
24 months steady qualities of experiment, therefore minimum 24 months of this product term of validity, long term test is still during continuing to investigate.
Experiment five：Taste, mouthfeel market survey
A kind of levo-oxiracetam effervescent tablet in good taste of the present invention is by specific supplementary material compatibility, by multiple seasoning
It is made, with excellent taste, taste is fragrant and sweet, can be received by many patients.
Method：The people of crowd 1000 of random selection more than 10 years old, carries out taste trial test, will now taste result statistics as follows
Table：
Levo-oxiracetam effervescent tablet taste application form
| It is very good | Preferably | Typically | Difference |
| 689 | 117 | 135 | 59 |
It can be seen from taste tastes market survey, this product is easy to be received by many patients, according to incompletely statistics, feels taste
Road is extraordinary to account for the 68.9% of whole crowd, feel taste it is relatively good account for 11.7%, feel taste it is general account for 13.5%,
Think that distasteful accounts for 5.9%.Therefore this product have it is in good taste, easily the characteristics of received by many patients colony.
Embodiment 2
A kind of delicious levo-oxiracetam effervescent tablet, is obtained according to the following steps：
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 check and sample stability experiment that measurement result table is tested at not sub- angle
Bright this product mobility of particle is good, and not sub- angle is less than 35 °, and tablet weight variation experiment shows that this product tablet weight variation, less than 2%, collapses
Solution overtime check result shows that this product disintegration time is respectively less than 30 seconds, and stability test result shows to accelerate 6 lunar sample qualities
Amount stabilization, long-term 24 months steady qualities, therefore this product term of validity at least 24 months, mouthfeel the survey showed that this product mouthful
Feel, easily received by many patients.
Embodiment 3
A kind of delicious levo-oxiracetam effervescent tablet, is obtained according to the following steps：
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 check and sample stability experiment that measurement result table is tested at not sub- angle
Bright this product mobility of particle is good, and not sub- angle is less than 34 °, and tablet weight variation experiment shows that this product tablet weight variation, less than 3%, collapses
Solution overtime check result shows that this product disintegration time is respectively less than 30 seconds, and stability test result shows to accelerate 6 lunar sample qualities
Amount stabilization, long-term 24 months steady qualities, therefore this product term of validity at least 24 months, mouthfeel the survey showed that this product mouthful
Feel, easily received by many patients.
Embodiment 4-6：A kind of delicious levo-oxiracetam effervescent tablet, is prepared by the supplementary material of following weight,
Preparation method is with embodiment 1：
| Embodiment | 4 | 5 | 6 |
| Levo-oxiracetam | 1 part | 1 part | 1 part |
| Tartaric acid | 6 parts | 7 parts | 8 parts |
| Sodium acid carbonate | 6 parts | 7 parts | 8 parts |
| Sodium chloride | 0.7 part | 0.6 part | 0.5 part |
| Macrogol 6000 | 1.05 parts | 0.9 part | 0.75 part |
| Macrogol 4000 | 1.1 parts | 1.0 parts | 0.9 part |
| Dextrin | 5 parts | 4 parts | 3 parts |
| Sucralose | 0.6 part | 0.5 part | 0.4 part |
| Peppermint oil | 0.4 | 0.4 | 0.4 |
| Strawberry essence | 0.4 | 0.3 | 0.4 |
| The ethanol solution of volume fraction 80% | 19 parts | 20 parts | 21 parts |
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, by embodiment 4,5,
6 carry out particle respectively stops sub- angle measure, tablet weight variation inspection, disintegration time limited inspection and sample stability experiment, implements
The prepared product of example 4,5,6 is stopped sub- angle experiment measurement result and shows that this product mobility of particle is good, and not sub- angle is respectively less than 35 °,
The experiment of the tablet weight variation of embodiment 4,5,6 shows this product tablet weight variation less than 3%, the inspection of the disintegration time limited of embodiment 4,5,6
The fruit that comes to an end shows that this product disintegration time is respectively less than 30 seconds, and the stability test result of embodiment 4,5,6 shows to accelerate June
Sample quality stabilization, long-term 24 months steady qualities, therefore this product term of validity at least 24 months, 4,5,6 mouthfuls of embodiment
The survey showed that this product is in good taste for sense, is easily received by many patients.
Claims (3)
1. a kind of delicious levo-oxiracetam effervescent tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：1 part or so of levo-oxiracetam, 5 ~ 9 parts or so of tartaric acid, 5 ~ 9 parts or so of sodium acid carbonate, 0.3 ~ 0.8 part or so of sodium chloride, 0.45 ~ 1.2 part or so of Macrogol 6000,0.8 ~ 1.3 part or so of Macrogol 4000,2 ~ 7 parts or so of dextrin, 0.3 ~ 0.8 part or so of Sucralose, 0.2 ~ 0.7 part or so of peppermint oil, 0.1 ~ 0.6 part or so of strawberry essence, volume fraction are 15 ~ 25 parts or so of 70% ~ 90% ethanol solution；The dextrin for taking recipe quantity is placed in and mills; the purified water of the quality such as addition; mill mixing; the peppermint oil and strawberry essence of recipe quantity are added in operating process; continue to mill 10 ~ 20 minutes; take out; it is placed in air dry oven; set 40 DEG C ~ 50 DEG C dryings of drying temperature to moisture to be taken out less than 3%, be placed in Universalpulverizer, add levo-oxiracetam, tartaric acid, the Sucralose of recipe quantity; co-grinding; 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：1 part or so of levo-oxiracetam, 6 ~ 8 parts or so of tartaric acid, 6 ~ 8 parts or so of sodium acid carbonate, 0.5 ~ 0.7 part or so of sodium chloride, 0.75 ~ 1.05 part or so of Macrogol 6000（Sodium chloride：Macrogol 6000=2:3）, 0.9 ~ 1.1 part or so of Macrogol 4000,3 ~ 5 parts or so of dextrin, 0.4 ~ 0.6 part or so of Sucralose, 0.3 ~ 0.5 part or so of peppermint oil, 0.2 ~ 0.5 part or so of strawberry essence, volume fraction be 18 ~ 23 parts or so of 70% ~ 90% ethanol solution；The dextrin for taking recipe quantity is placed in and mills; the purified water of the quality such as addition; mill mixing; the peppermint oil and strawberry essence of recipe quantity are added in operating process; continue to mill 10 ~ 20 minutes; take out; it is placed in air dry oven; set 45 DEG C of dryings of drying temperature to moisture to be taken out less than 3%, be placed in Universalpulverizer, add levo-oxiracetam, tartaric acid, the Sucralose of recipe quantity; co-grinding; 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. the dextrin for taking recipe quantity is placed in and mills; the purified water of the quality such as addition; mill mixing; the peppermint oil and strawberry essence of recipe quantity are added in operating process; continue to mill 10 ~ 20 minutes; take out; it is placed in air dry oven; set 45 DEG C of dryings of drying temperature to moisture to be taken out less than 3%, be placed in Universalpulverizer, add levo-oxiracetam, tartaric acid, the Sucralose of recipe quantity; co-grinding; 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. 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；
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 20 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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| CN201510946685.3A CN106902091A (en) | 2015-12-17 | 2015-12-17 | A kind of delicious levo-oxiracetam effervescent tablet and preparation method thereof |
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| CN201510946685.3A CN106902091A (en) | 2015-12-17 | 2015-12-17 | A kind of delicious levo-oxiracetam effervescent tablet and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2044216A5 (en) * | 1969-05-12 | 1971-02-19 | Ile De France | Effervescent tablets prepd by aqueous - granulation |
| 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 |
| 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 |
| CN103301114A (en) * | 2012-03-07 | 2013-09-18 | 辽宁亿灵科创生物医药科技有限公司 | Oxiracetam medicinal composition, and preparation method and application thereof |
-
2015
- 2015-12-17 CN CN201510946685.3A patent/CN106902091A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2044216A5 (en) * | 1969-05-12 | 1971-02-19 | Ile De France | Effervescent tablets prepd by aqueous - granulation |
| 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 |
| 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 |
| CN103301114A (en) * | 2012-03-07 | 2013-09-18 | 辽宁亿灵科创生物医药科技有限公司 | Oxiracetam medicinal composition, and preparation method and application thereof |
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Application publication date: 20170630 |