CN106902092A - A kind of disintegration is fast（S）Oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 and preparation method thereof - Google Patents
A kind of disintegration is fast（S）Oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 and preparation method thereof Download PDFInfo
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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
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Abstract
It is a kind of（S）The pyrrolidine acetamide effervescent tablet of 4 hydroxyl, 2 oxo 1, it is obtained by following supplementary material：（S）1 part of 4 hydroxyl, 2 oxo, 1 pyrrolidine acetamide, 5 ~ 9 parts of tartaric acid, 5 ~ 9 parts of sodium acid carbonate, 0.2 ~ 0.7 part of sodium chloride, 0.3 ~ 1.05 part of Macrogol 6000,5 ~ 10 parts of dextrin, 0.7 ~ 1.2 part of Sucralose, 0.3 ~ 0.8 part of peppermint oil, 0.3 ~ 0.8 part of strawberry essence, volume fraction are 30% ~ 50% 18 ~ 25 parts of ethanol solution, 3 ~ 5 parts of sodium carboxymethylcellulose, 6 ~ 12 parts of microcrystalline cellulose；According to obtained in the present invention（S）The pyrrolidine acetamide effervescent tablet tableting processes of 4 hydroxyl, 2 oxo 1 will not sticking, finished product aerogenesis is fast, and disintegration is fast, and storage process is difficult moisture absorption and goes bad, it is easy to preserves, this product is in good taste, is easily received by most of patient, shelf life is 30 months.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of fast oxo -1- pyrroles of (S) -4- hydroxyls -2 of disintegration
Alkyl acetamide effervescent tablet and preparation method thereof.
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.
The existing oxo-1-pyrrolidine ethanamide effervescent formulation of (S) -4- hydroxyls -2 be primarily present the easy sticking of tableting processes, into
Product aerogenesis is slow, disintegration is slow, and easily the moisture absorption is rotten and cause stability poor during product storage, and shelf life is short, finished product mouth
Sense is poor, is difficult the technical problem such as to receive by many patients.
The content of the invention
It is an object of the invention to provide a kind of OXo-1-pyrrolidine acetyl of (S) -4- hydroxyls -2 for being disintegrated fast, good stability
Amine effervescent tablet.
Preparation another object of the present invention is to provide the above-mentioned oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2
Method.
The purpose of the present invention is realized by following technical measures：
It is a kind of to be disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, it is characterised in that it is with (S)
The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 be raw material, add a certain amount of acid source, alkali source, adhesive, lubricant,
Filler, flavouring are obtained；Wherein described acid source is in citric acid, tartaric acid, fumaric acid, adipic acid, malic acid
It is a kind of；The alkali source is the one kind in sodium carbonate, sodium acid carbonate, potassium carbonate, saleratus, calcium carbonate；The bonding
Agent is one or more in water, ethanol, sucrose, starch slurry, dextrin, copolyvidone VA64 (PVP/VA64)；It is described
Lubricant is talcum powder, magnesium stearate, Macrogol 4000, Macrogol 6000, stearic acid, calcium stearate, dodecyl
One or more in sodium sulphate, superfine silica gel powder, magnesia, paraffin；Filler is starch, lactose, dextrin, Icing Sugar, sulphur
One or more in sour calcium, sucrose, mannitol, microcrystalline cellulose, glucose, sodium carboxymethylcellulose, sodium chloride；It is described
Flavouring is sucrose, maltose, ethylmaltol, Sucralose, sweet stevia rebaudianum, sorbierite, mannitol, glucose, A Si
One or more in Pa Tan, peppermint oil, strawberry essence, apple banana, peach flavor, chocolate essence.
Inventor has found in research process, suitable supplementary product kind and specific supplementary material consumption proportion relation, then matches somebody with somebody
Special preparation method is closed, the oxo-1-pyrrolidine ethanamide effervescent tablet tableting processes of above-mentioned (S) -4- hydroxyls -2 is may be such that not
Meeting sticking, finished product aerogenesis is fast, and disintegration is fast, and product storage process is difficult the moisture absorption, and good stability, finished product is in good taste；It is above-mentioned
(S) the oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2, it is characterised in that it is by the former auxiliary of following weight proportion
Material is obtained：(S) 1 part of -2 oxo-1-pyrrolidine ethanamide of -4- hydroxyls, 5~9 parts of tartaric acid, 5~9 parts of sodium acid carbonate,
It is 0.2~0.7 part of sodium chloride, 0.3~1.05 part of Macrogol 6000,5~10 parts of dextrin, 0.7~1.2 part of Sucralose, thin
0.3~0.8 part of lotus oil, 0.3~0.8 part of strawberry essence, 18~25 parts of ethanol solution, the carboxylic that volume fraction is 30%~50%
3~5 parts of sodium carboxymethylcellulose pyce, 6~12 parts of microcrystalline cellulose；The dextrin for taking recipe quantity is placed in and mills, and the quality such as adds
Purified water, mixing of milling, in operating process add recipe quantity peppermint oil and strawberry essence, continue to mill 10~20 points
Clock, takes out, and is placed in air dry oven, sets 40 DEG C~50 DEG C dryings of drying temperature to moisture and is taken out less than 3%, is placed in
In Universalpulverizer, add the oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 of recipe quantity, tartaric acid, Sucralose,
Sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mixed-powder is collected after crossing 100 mesh sieves, and mixed-powder is placed in
Adhesive is added in wet granulator, starts granulator (installing 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 Universalpulverizer and is crushed, mixed powder is collected after crossing 100 mesh sieves
End, it is standby；The Macrogol 6000 of recipe quantity is heated into fusing, 40~45 DEG C of fusion temperature is set, polyethylene glycol is treated
After 6000 fusings, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, be uniformly mixed, be placed in after cooling omnipotent
In pulverizer, crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator, start granulator and (install 18
Mesh nylon mesh), granulation obtains alkali phase particle, standby.
In order to further speed up the oxo-1-pyrrolidine ethanamide Effervescent tablet disintegration aerogenesis speed of (S) -4- hydroxyls -2, improve into
Product stability, extends shelf life so that finished product taste is more preferable, the OXo-1-pyrrolidine second of one kind (S) -4- hydroxyls -2
Acid amides effervescent tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：(S) oxo -1- of -4- hydroxyls -2
1 part of pyrrolidine acetamide, 6~8 parts of tartaric acid, 6~8 parts of sodium acid carbonate, 0.3~0.5 part of sodium chloride, Macrogol 6000
0.45~0.75 part (sodium chloride: Macrogol 6000=2: 3), 7~9 parts of dextrin, 0.9~1.1 part of Sucralose, peppermint
0.5~0.7 part of oil, 0.5~0.8 part of strawberry essence, 19~23 parts of ethanol solution, the carboxylic first that volume fraction is 30%~50%
3~5 parts of base sodium cellulosate, 7~10 parts of microcrystalline cellulose；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, 45 DEG C of dryings of drying temperature to moisture is set and is taken out less than 3%, be placed in omnipotent crushing
In machine, the oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2, tartaric acid, Sucralose, the carboxymethyl of recipe quantity are added
Sodium cellulosate, microcrystalline cellulose co-grinding, 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；Take place
The sodium acid carbonate of side's amount, sodium chloride mixing, are placed in Universalpulverizer and crush, and mixed-powder is collected after crossing 100 mesh sieves,
It is standby；The Macrogol 6000 of recipe quantity is heated into fusing, 42 DEG C of fusion temperature is set, treats that Macrogol 6000 melts
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.
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 for being disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, it is characterised in that
It is obtained as follows：
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, adds (the S) -4- hydroxyls -2 of recipe quantity
Oxo-1-pyrrolidine ethanamide, tartaric acid, Sucralose, sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mistake
Mixed-powder is collected after 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；
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；The Macrogol 6000 of recipe quantity is heated into fusing, 42 DEG C of fusion temperature is set, poly- second two is treated
After alcohol 6000 melts, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, be uniformly mixed, be placed in after cooling
In Universalpulverizer, crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator, start granulator and (install
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：(S) the oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 is packed with Aluminium-coating Packer, setting packaging rule
Lattice are 6 sheet panels, and below 25 DEG C of environment temperature of control, below 30%, packaging is obtained final product relative humidity.
The present invention has following beneficial effect：
The present invention is a kind of be disintegrated fast oxo-1-pyrrolidine ethanamide effervescent tablet tableting processes of (S) -4- hydroxyls -2 will not sticking,
Finished product aerogenesis is fast, and disintegration rate is fast, and not over 30 seconds, product storage process was difficult moisture absorption and goes bad disintegration time, easily
In preservation, and this product is in good taste, is easily received by most of patient, and shelf life is 30 months, preparation technology
Simple possible, 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
It is a kind of to be disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, it is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 1 part |
| Tartaric acid | 6 parts |
| Sodium acid carbonate | 6 parts |
| Sodium chloride | 0.3 part |
| Macrogol 6000 | 0.45 part |
| Dextrin | 7 parts |
| Sucralose | 0.9 part |
| Peppermint oil | 0.5 part |
| Strawberry essence | 0.5 part |
| Volume fraction is 30% ethanol | 19 parts |
| Sodium carboxymethylcellulose | 3 parts |
| Microcrystalline cellulose | 7 parts |
It is made 1000
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, adds (the S) -4- hydroxyls -2 of recipe quantity
Oxo-1-pyrrolidine ethanamide, tartaric acid, Sucralose, sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mistake
Mixed-powder is collected after 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；
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；The Macrogol 6000 of recipe quantity is heated into fusing, 42 DEG C of fusion temperature is set, poly- second two is treated
After alcohol 6000 melts, the mixed-powder of above-mentioned sodium acid carbonate and sodium chloride is added, be uniformly mixed, be placed in after cooling
In Universalpulverizer, crush, be placed in after 100 mesh sieves excessively and adhesive is added in wet granulator, start granulator and (install
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：(S) the oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 is packed with Aluminium-coating Packer, setting packaging rule
Lattice are 6 sheet panels, and below 25 DEG C of environment temperature of control, below 30%, packaging is obtained final product relative humidity.
Experiment one：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 1.9% and 2.5%, thus product moisture absorption weightening compared with
It is small, it is easy to preserve.
Experiment two：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) | 21 | 26 | 22 | 19 | 28 |
| Sample number into spectrum | 6# | 7# | 8# | 9# | 10# |
| Disintegration time | 25 | 23 | 21 | 26 | 23 |
4. conclusion (of pressure testing)：From upper table result of the test, the oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2 collapses
The solution time is respectively less than 30s.
Experiment three：Stability experiment
Experiment material：
(S) the oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2：For embodiment 1 is obtained.
Acceleration study method：By the oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2 obtained in embodiment 1 by upper
City is packed, and puts in Acceleration study case, and 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：The oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 obtained in embodiment 1 is packed by listing,
Put in the long-term case that keeps sample, 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.
Experiment four：Taste, mouthfeel market survey
The oxo-1-pyrrolidine ethanamide effervescent tablet of the present invention (S) -4- hydroxyls -2 be by specific supplementary material compatibility, it is various to rectify
Taste agent coordinates and is made, and 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：
(S) the oxo-1-pyrrolidine ethanamide effervescent tablet taste application form of -4- hydroxyls -2
| It is very good | Preferably | Typically | Difference |
| 591 | 158 | 132 | 119 |
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 59.1% of whole crowd, feel taste it is relatively good account for 15.8%, feel taste it is general account for 13.2%,
Think that distasteful accounts for 11.9%.Therefore this product have it is in good taste, easily the characteristics of received by many patients colony.
Embodiment 2
It is a kind of to be disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, it is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 1 part |
| Tartaric acid | 8 parts |
| Sodium acid carbonate | 8 parts |
| Sodium chloride | 0.5 part |
| Macrogol 6000 | 0.75 part |
| Dextrin | 9 parts |
| Sucralose | 1.1 parts |
| Peppermint oil | 0.7 part |
| Strawberry essence | 0.8 part |
| Volume fraction is 50% ethanol | 23 parts |
| Sodium carboxymethylcellulose | 5 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, moisture absorption increasing is carried out respectively
Resurveying, fixed, disintegration time limited is checked, sample stability experiment and mouthfeel are investigated, and relative humidity 75% places 10 days products
Moisture absorption rate of body weight gain is 1.6%, and it is 2.3% that relative humidity 92.5% places 10 days product moisture absorption rates of body weight gain, shows that finished product is difficult
Moisture absorption, disintegration time limited inspection result shows that this product disintegration time is respectively less than 30 seconds, and stability test result shows acceleration 6
Month sample quality stabilization, long-term 30 months steady qualities, therefore this product term of validity at least 30 months, mouthfeel investigation result table
Bright this product is in good taste, is easily received by many patients.
Embodiment 3
It is a kind of to be disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, it is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 1 part |
| Tartaric acid | 7 parts |
| Sodium acid carbonate | 7 parts |
| Sodium chloride | 0.4 part |
| Macrogol 6000 | 0.6 part |
| Dextrin | 8 parts |
| Sucralose | 1.0 parts |
| Peppermint oil | 0.6 part |
| Strawberry essence | 0.7 part |
| Volume fraction is 40% ethanol | 21 parts |
| Sodium carboxymethylcellulose | 4 parts |
| Microcrystalline cellulose | 8 parts |
It is made 1000
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, moisture absorption increasing is carried out respectively
Resurveying, fixed, disintegration time limited is checked, sample stability experiment and mouthfeel are investigated, and relative humidity 75% places 10 days products
Moisture absorption rate of body weight gain is 1.8%, and it is 2.4% that relative humidity 92.5% places 10 days product moisture absorption rates of body weight gain, shows that finished product is difficult
Moisture absorption, disintegration time limited inspection result shows that this product disintegration time is respectively less than 30 seconds, and stability test result shows acceleration 6
Month sample quality stabilization, long-term 30 months steady qualities, therefore this product term of validity at least 30 months, mouthfeel investigation result table
Bright this product is in good taste, is easily received by many patients.
Embodiment 4-6：It is a kind of to be disintegrated the fast oxo-1-pyrrolidine ethanamide effervescent tablet of (S) -4- hydroxyls -2, by following heavy
The supplementary material of amount is prepared, and preparation method is with embodiment 1：
Preparation process：Preparation technology according to embodiment 1 is obtained.By the test method of embodiment 1, moisture absorption increasing is carried out respectively
Resurveying, fixed, disintegration time limited is checked, sample stability experiment and mouthfeel are investigated, and embodiment 4,5,6 is in relative humidity 75%
Place 10 days product moisture absorption rates of body weight gain and be respectively 1.6%, 1.5%, 1.8%, embodiment 4,5,6 is in relative humidity 92.5%
Place 10 days product moisture absorption rates of body weight gain and be respectively 2.3%, 2.1%, 2.6%, show that finished product is difficult moisture absorption, embodiment 4,5,
6 disintegration time limited inspection results show that this product disintegration time is respectively less than 30 seconds, the stability test result table of embodiment 4,5,6
Bright acceleration June sample quality stabilization, long-term 30 months steady qualities, therefore this product term of validity at least 30 months, embodiment
4th, the survey showed that this product is in good taste for 5,6 mouthfeels, is easily received by many patients.
Claims (3)
1. a kind of disintegration is fast（S）The oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2, it is characterised in that it is obtained by the supplementary material of following weight proportion：（S）1 part of -2 oxo-1-pyrrolidine ethanamide of -4- hydroxyls, 5 ~ 9 parts of tartaric acid, 5 ~ 9 parts of sodium acid carbonate, 0.2 ~ 0.7 part of sodium chloride, 0.3 ~ 1.05 part of Macrogol 6000,5 ~ 10 parts of dextrin, 0.7 ~ 1.2 part of Sucralose, 0.3 ~ 0.8 part of peppermint oil, 0.3 ~ 0.8 part of strawberry essence, volume fraction are 30% ~ 50% 18 ~ 25 parts of ethanol solution, 3 ~ 5 parts of sodium carboxymethylcellulose, 6 ~ 12 parts of microcrystalline cellulose；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, continues to mill 10 ~ 20 minutes, taken 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 recipe quantity（S）The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, tartaric acid, Sucralose, sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mixed-powder is collected after crossing 100 mesh sieves, mixed-powder is placed in adhesive is added in wet granulator, starts 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；The Macrogol 6000 of recipe quantity is heated into fusing; 40 ~ 45 DEG C of fusion temperature of setting; after after Macrogol 6000 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. as claimed in claim 1（S）The oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2, it is characterised in that it is obtained by the supplementary material of following weight proportion：（S）1 part of -2 oxo-1-pyrrolidine ethanamide of -4- hydroxyls, 6 ~ 8 parts of tartaric acid, 6 ~ 8 parts of sodium acid carbonate, 0.3 ~ 0.5 part of sodium chloride, 0.45 ~ 0.75 part of Macrogol 6000（Sodium chloride：Macrogol 6000=2:3）, 7 ~ 9 parts of dextrin, 0.9 ~ 1.1 part of Sucralose, 0.5 ~ 0.7 part of peppermint oil, 0.5 ~ 0.8 part of strawberry essence, volume fraction for 30% ~ 50% 19 ~ 23 parts of ethanol solution, 3 ~ 5 parts of sodium carboxymethylcellulose, 7 ~ 10 parts of microcrystalline cellulose；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, continues to mill 10 ~ 20 minutes, taken 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 recipe quantity（S）The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, tartaric acid, Sucralose, sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mixed-powder is collected after crossing 100 mesh sieves, mixed-powder is placed in adhesive is added in wet granulator, starts 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；The Macrogol 6000 of recipe quantity is heated into fusing; 42 DEG C of fusion temperature of setting; after after Macrogol 6000 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. as claimed in claim 1 or 2（S）The preparation method of the oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -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, continues to mill 10 ~ 20 minutes, taken 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 recipe quantity（S）The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, tartaric acid, Sucralose, sodium carboxymethylcellulose, microcrystalline cellulose co-grinding, mixed-powder is collected after crossing 100 mesh sieves, mixed-powder is placed in adhesive is added in wet granulator, starts 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；The Macrogol 6000 of recipe quantity is heated into fusing; 42 DEG C of fusion temperature of setting; after after Macrogol 6000 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：（S）The oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 is packed with Aluminium-coating Packer, sets packing specification as 6 sheet panels, and below 25 DEG C of environment temperature of control, below 30%, packaging is obtained final product relative humidity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510946805.XA CN106902092A (en) | 2015-12-17 | 2015-12-17 | A kind of disintegration is fast（S）Oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510946805.XA CN106902092A (en) | 2015-12-17 | 2015-12-17 | A kind of disintegration is fast（S）Oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN106902092A true CN106902092A (en) | 2017-06-30 |
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|---|---|---|---|
| CN201510946805.XA Withdrawn CN106902092A (en) | 2015-12-17 | 2015-12-17 | A kind of disintegration is fast（S）Oxo-1-pyrrolidine ethanamide effervescent tablet of -4- hydroxyls -2 and preparation method thereof |
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| CN (1) | CN106902092A (en) |
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 CN201510946805.XA patent/CN106902092A/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 |