CN106619524A - Good-stability sinistral oxiracetam and preparation method thereof - Google Patents
Good-stability sinistral oxiracetam and preparation method thereof Download PDFInfo
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Abstract
The invention discloses good-stability sinistral oxiracetam granules which are characterized by being prepared from the following raw materials and auxiliary materials in parts by weight: about 1 part of sinistral oxiracetam, about 0.7-1.3 parts of mannitol, about 0.5-1.0 part of microcrystalline cellulose, about 0.7-1.2 parts of sodium carboxymethylcellulose, about 0.8-1.3 parts of lactose, about 0.07-0.12 part of magnesium stearate, about 0.8-1.5 part of polyethylene glycol 4000, about 0.6-1.1 parts of hydroxypropyl methylcellulose, about 5-12 parts of a 50-70% ethanol solution, about 1-6 parts of cane sugar and about 0.02-0.06 part of ethyl maltol. The good-stability sinistral oxiracetam granules disclosed by the invention are good in storage stability, not liable to moisten or cake, good in taste, acceptable by most patients, simple and feasible in preparation process and worthy of market popularization, and the product shelf life is as long as 36 months.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of levo-oxiracetam particle of good stability and its system
Preparation Method.
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 itself without direct vasoactive, also without in
Pivot excitation, the impact to ability of learning and memory is a kind of lasting facilitation.
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 synthesis can be promoted, 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 configurations (left-handed)
The drug effect of Oxiracetam is better than R configurations (dextrorotation), and Oxiracetam and levo-oxiracetam structure are as follows.
Existing levo-oxiracetam particle is primarily present that storage process stability is poor, and particle hygroscopicity is strong, connecting block easy to stick,
Shelf life is short, and particle mouthfeel is poor, the technical problem such as is difficult to be easily accepted by the patient.
The content of the invention
It is an object of the invention to provide a kind of good stability, levo-oxiracetam particle in good taste.
Another object of the present invention is to provide the preparation method of above-mentioned levo-oxiracetam particle.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam particle, it is, with levo-oxiracetam as raw material, to add a certain amount of filler, rectify
Taste agent, adhesive, lubricant, disintegrant, coating material are obtained；Wherein described filler be starch, lactose, dextrin,
One or more in Icing Sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose, glucose, sodium carboxymethylcellulose；It is described
Flavouring is sucrose, maltose, ethylmaltol, Sucralose, sweet stevia rebaudianum, sorbierite, mannitol, glucose, A Si
One or more during handkerchief is smooth；Described adhesive is water, ethanol, sucrose, starch slurry, dextrin, carboxymethylcellulose calcium, poly- second
One or more in alkene pyrrolidone；The lubricant is talcum powder, magnesium stearate, polyethylene glycol, stearic acid, stearic acid
One or more in calcium, lauryl sodium sulfate, superfine silica gel powder, magnesia, paraffin；The disintegrant is low-substituted hydroxypropyl
One or more in base cellulose, polyoxyethylene sorbitan monoleate, sodium carboxymethyl starch, dried starch；The coating material is poly- second two
Alcohol 4000, Macrogol 6000, hydroxypropyl cellulose, Hydroxypropyl methylcellulose, AEA, hydroxypropyl first
One or more in base cellulose phthalate.
Inventor has found in research process, the compound coating material of Macrogol 4000 and Hydroxypropyl methylcellulose composition,
The certain auxiliary material of cooperation and specific preparation method, can cause above-mentioned levo-oxiracetam particle to be difficult moisture absorption, not easy to stick
Connecting block, product stability are good, and shelf life is long, and particle is delicious；The good levo-oxiracetam particle of aforementioned stable,
Characterized in that, it is obtained by the supplementary material of following weight proportion：1 part of levo-oxiracetam, mannitol 0.7～1.3
Part, 0.5～1.0 part of microcrystalline cellulose, 0.7～1.2 part of sodium carboxymethylcellulose, 0.8～1.3 part of lactose, magnesium stearate
0.07～0.12 part, 0.8～1.5 part of Macrogol 4000,0.6～1.1 part of Hydroxypropyl methylcellulose, volume fraction be 50%～70%
5～12 parts of ethanol solution, 1～6 part of sucrose, 0.02～0.06 part of ethylmaltol；Take levo-oxiracetam, mannitol,
Microcrystalline cellulose, sodium carboxymethylcellulose, lactose, sucrose, ethylmaltol are placed in Universalpulverizer, crush 100
It is placed in after mesh sieve in wet granulator, adds adhesive, start granulator (installing 24 mesh nylon mesh), starts granulation；
Obtained wet granular is put in air dry oven, setting temperature 50 C～60 DEG C drying time is 120min～150min,
So that particle water content≤3% (weight/mass percentage composition)；Coating material is taken, is added water and is made quality volume fraction for 6%～9%
Coating solution, it is standby；Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40～50
℃；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity, atomization is set
Pressure is 0.8～1.0bar, continues air intake and is dried, and solution stops heating, cooling after continuing to heat 10～15 minutes after having sprayed
Discharging, obtains final product coated granule.
Further, in order to further improve the mouthfeel of levo-oxiracetam particle, granule stability is improved, extends shelf
Phase；Above-mentioned levo-oxiracetam particle, it is characterised in that it is obtained by the supplementary material of following weight proportion：Left-handed Austria
1 part of La Xitan, 0.8～1.1 part of mannitol, 0.6～0.9 part of microcrystalline cellulose, 0.8～1.1 part of sodium carboxymethylcellulose,
0.9～1.2 part of lactose, 0.09～0.11 part of magnesium stearate, 0.9～1.3 part of Macrogol 4000, Hydroxypropyl methylcellulose 0.8～1.0
Part, 7～10 parts of ethanol solution, 2～5 parts of sucrose, 0.03～0.05 part of the ethylmaltol that volume fraction is 50%～70%；
Take levo-oxiracetam, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose, sucrose, ethylmaltol to put
In Universalpulverizer, crushed and be placed in after 100 mesh sieves in wet granulator, added adhesive, started granulator (peace
Fill 24 mesh nylon mesh), start granulation；Obtained wet granular is put in air dry oven, temperature 50 C～60 DEG C are set
Drying time is 120min～150min so that particle water content≤3% (weight/mass percentage composition)；Coating material is taken, plus
Water makes the coating solution that quality volume fraction is 6%～9%, standby；Above-mentioned dry particl is put in fluid bed, heat is passed through
Air, is allowed to suspension fluidization, and bed temperature is 40～50 DEG C；Coating solution is continuously added to into fluidisation by the nozzle atomization of fluid bed
Bed, setting 50～60rpm of spouting velocity, atomizing pressure is 0.8～1.0bar, continues air intake and is dried, and solution continues after having sprayed
Heating stops heating after 10～15 minutes, and cooling discharging obtains final product coated granule.
The preparation method of the levo-oxiracetam particle of a kind of good stability, it is characterised in that it is prepared as follows
's：
1. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, filler, flavouring, disintegrant and be placed in omnipotent powder
In broken machine, 100 mesh sieves were crushed, it is standby；
2. pelletize：Gained mixed-powder after pre-treatment is taken, in being placed in wet granulator, adhesive is added, starts granulator
(installing 24 mesh nylon mesh), starts granulation；
3. it is dried：It is by temperature 50 C～60 DEG C drying time in wet granular input air dry oven, is arranged
120min～150min so that particle water content≤3% (weight/mass percentage composition)；
4. coating：
(1) configuration of coating solution：The coating material of recipe quantity is taken, add water the coating solution for making that quality volume fraction is 6%～9%,
It is standby；
(2) coating process：Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40～50
℃；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity, atomization is set
Pressure is 0.8～1.0bar, continues air intake and is dried, and solution stops heating, cooling after continuing to heat 10～15 minutes after having sprayed
Discharging, obtains final product coated granule；
5. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, is sieved whole grain with 24 mesh nylon mesh, control environment
Below 25 DEG C of temperature, relative humidity is below 50%；
6. total mixed：Lubricant was crushed into 100 mesh sieves, in adding the particle after whole grain, was mixed with three-dimensional motion mixer
10min～20min；
7. bag in：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control,
Below relative humidity 50%, obtain final product.
The present invention has following beneficial effect：
Obtained levo-oxiracetam particle of the invention has storage process stability good, and product is difficult moisture absorption caking, product
Shelf life is up to 36 months, in good taste, can be received by most of patient, and preparation process is simple is feasible, is worth market
Promote.
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 made to the inventive method, step or condition or replacement belong to the scope of the present invention.
Embodiment 1
A kind of levo-oxiracetam particle of good stability, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Mannitol | 0.8 part |
| Microcrystalline cellulose | 0.6 part |
| Sodium carboxymethylcellulose | 0.8 part |
| Lactose | 0.9 part |
| Magnesium stearate | 0.09 part |
| Macrogol 4000 | 0.9 part |
| Hydroxypropyl methylcellulose | 0.8 part |
| Sucrose | 2 parts |
| Ethylmaltol | 0.03 part |
| The ethanol solution of volume fraction 50% | 7 parts |
Make 1000 bags
Preparation process：
1. supplementary material pre-treatment：Take levo-oxiracetam, mannitol, microcrystalline cellulose, the carboxymethylcellulose calcium of recipe quantity
Sodium, lactose, sucrose, ethylmaltol are placed in Universalpulverizer, crush 100 mesh sieves, standby；
2. pelletize：Gained mixed-powder after pre-treatment is taken, in being placed in wet granulator, the volume fraction 50% of recipe quantity is added
Ethanol solution, start granulator (install 24 mesh nylon mesh), start granulation；
3. it is dried：It is by temperature 50 C～60 DEG C drying time in wet granular input air dry oven, is arranged
120min～150min so that particle water content≤3% (weight/mass percentage composition)；
4. coating：
(1) configuration of coating solution：Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, is added water and is made quality volume integral
Number is 6%～9% coating solution, standby；
(2) coating process：Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40～50
℃；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity, atomization is set
Pressure is 0.8～1.0bar, continues air intake and is dried, and solution stops heating, cooling after continuing to heat 10～15 minutes after having sprayed
Discharging, obtains final product coated granule；
5. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, is sieved whole grain with 24 mesh nylon mesh, control environment
Below 25 DEG C of temperature, relative humidity is below 50%；
6. total mixed：Magnesium stearate was crushed into 100 mesh sieves, it is mixed with three-dimensional motion mixer in adding the particle after whole grain
Close 10min～20min；
7. bag in：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control,
Below relative humidity 50%, obtain final product.
Test one：Taste, mouthfeel market survey
A kind of levo-oxiracetam particle of good stability of the present invention is through specific supplementary material compatibility, through multiple seasoning
Make, with excellent taste, taste is fragrant and sweet, can be received by extensive patients.
Method：The random selection people of crowd 1000 of more than 10 years old, carries out taste trial test, will now taste result statistics as follows
Table：
Levo-oxiracetam particle taste application form
| It is very good | Preferably | Typically | Difference |
| 638 | 169 | 152 | 41 |
It can be seen from taste tastes market survey, this product is easy to be received by extensive patients, according to incompletely statistics, feels taste
Road is extraordinary to account for the 63.8% of whole crowd, thinks that taste is reasonable and accounts for 16.9%, feel taste it is general account for 15.2%,
Think that distasteful accounts for 4.1%.Therefore this product have it is in good taste, the characteristics of easily acceptance by extensive patients colony.
Test two：A kind of levo-oxiracetam granule stability experiment of good stability of the present invention
Experiment material：
Levo-oxiracetam particle：It is obtained for embodiment 1.
Acceleration study method：By levo-oxiracetam particle obtained in embodiment 1 by listing packaging, in putting Acceleration study case,
Certain hour is sampled, and investigation project is tested.
Acceleration study temperature：40±2℃
Acceleration study humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：Proterties, moisture, granularity, melting, 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 stable, and this product stability is preferable.
Long-term experiment method：By levo-oxiracetam particle obtained in embodiment 1 by listing packaging, put and keep sample for a long time in case,
Certain hour is sampled, and investigation project is tested.
Long-term experiment temperature：25±2℃
Long-term experiment humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24,36 months
Inspection target：Proterties, moisture, granularity, melting, relevant material, content, microbial limit
Long term test stability is recorded：
Long term test shows：36 months proterties of this product long term test, moisture, granularity, melting, relevant material, contain
Amount, microbial limit without significant changes, meet every relevant regulations of production quality standard draft.This product is long-term
36 months steady qualities of test, therefore this product term of validity is minimum 36 months, long term test is still during continuing to investigate.
Embodiment 2
A kind of levo-oxiracetam particle of good stability, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Mannitol | 1.1 part |
| Microcrystalline cellulose | 0.9 part |
| Sodium carboxymethylcellulose | 1.1 part |
| Lactose | 1.2 part |
| Magnesium stearate | 0.11 part |
| Macrogol 4000 | 1.3 part |
| Hydroxypropyl methylcellulose | 1.0 part |
| Sucrose | 5 parts |
| Ethylmaltol | 0.05 part |
| The ethanol solution of volume fraction 50% | 10 parts |
Make 1000 bags
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, taste mouth is carried out respectively
Sense market survey and sample stability test, it is in good taste that taste mouthfeel market survey shows that this product has, easily by vast trouble
The characteristics of person colony receives；Stability test result shows to accelerate June sample quality to stablize, long-term 36 months quality
It is stable, therefore this product term of validity at least 36 months.
Embodiment 3
A kind of levo-oxiracetam particle of good stability, is obtained according to the following steps：
| Composition | Consumption |
| Levo-oxiracetam | 1 part |
| Mannitol | 0.9 part |
| Microcrystalline cellulose | 0.8 part |
| Sodium carboxymethylcellulose | 1.0 part |
| Lactose | 1.1 part |
| Magnesium stearate | 0.10 part |
| Macrogol 4000 | 1.1 part |
| Hydroxypropyl methylcellulose | 0.9 part |
| Sucrose | 3 parts |
| Ethylmaltol | 0.04 part |
| The ethanol solution of volume fraction 70% | 8 parts |
Make 1000 bags
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, taste mouth is carried out respectively
Sense market survey and sample stability test, it is in good taste that taste mouthfeel market survey shows that this product has, easily by vast trouble
The characteristics of person colony receives；Stability test result shows to accelerate June sample quality to stablize, long-term 36 months quality
It is stable, therefore this product term of validity at least 36 months.
Embodiment 4-6：The levo-oxiracetam particle that a kind of stability is acted charitably, 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 |
| Mannitol | 1.0 part | 0.9 part | 0.8 part |
| Microcrystalline cellulose | 0.6 part | 0.7 part | 0.8 part |
| Sodium carboxymethylcellulose | 1.1 part | 1.0 part | 0.9 part |
| Lactose | 1.0 part | 1.1 part | 1.2 part |
| Magnesium stearate | 0.10 part | 0.10 part | 0.10 part |
| Macrogol 4000 | 1.2 part | 1.1 part | 1.0 part |
| Hydroxypropyl methylcellulose | 1.0 part | 0.9 part | 0.9 part |
| Sucrose | 3 parts | 3 parts | 3 parts |
| Ethylmaltol | 0.03 part | 0.04 part | 0.05 part |
| The ethanol of volume fraction 60% | 9 parts | 8 parts | 8 parts |
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, by embodiment 4,5,
6 carry out respectively the market survey of taste mouthfeel and sample stability test, and taste mouthfeel market survey result shows embodiment
4th, 5,6 have it is in good taste, the characteristics of easily acceptance by extensive patients colony；The stability test of embodiment 4,5,6 is tied
Fruit shows to accelerate June sample quality to stablize, long-term 36 months steady qualities, therefore the sample obtained by embodiment 4,5,6
The product term of validity at least 36 months.
Claims (3)
1. the levo-oxiracetam particle of a kind of good stability, it is characterised in that it is by the supplementary material of following weight proportion
And following steps are obtained：About 1 part of levo-oxiracetam, about 0.7～1.3 part of mannitol, about 0.5～1.0 part of microcrystalline cellulose,
About 0.7～1.2 part of sodium carboxymethylcellulose, about 0.8～1.3 part of lactose, about 0.07～0.12 part of magnesium stearate, polyethylene glycol
4000 about 0.8～1.5 parts, about 0.6～1.1 part of Hydroxypropyl methylcellulose, the ethanol solution about 5～12 that volume fraction is 50%～70%
Part, about 1～6 part of sucrose, about 0.02～0.06 part of ethylmaltol；Take levo-oxiracetam, mannitol, microcrystalline cellulose
Element, sodium carboxymethylcellulose, lactose, sucrose, ethylmaltol are placed in Universalpulverizer, after crushing 100 mesh sieves
In being placed in wet granulator, adhesive is added, start granulator (installing 24 mesh nylon mesh), start granulation；To be obtained
Wet granular input air dry oven in, settings temperature 50 C～60 DEG C drying time be 120min～150min so that
Grain water content≤3% (weight/mass percentage composition)；Coating material is taken, add water the coating for making that quality volume fraction is 6%～9%
Liquid, it is standby；Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40～50 DEG C；
Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity, atomizing pressure is set
For 0.8～1.0bar, continue air intake and be dried, solution has sprayed and stopped heating after rear continuation is heated 10～15 minutes, cooling discharging,
Obtain final product coated granule.
2. levo-oxiracetam particle as claimed in claim 1, it is characterised in that it is by the original of following weight proportion
Auxiliary material and following steps are obtained：About 1 part of levo-oxiracetam, about 0.8～1.1 part of mannitol, microcrystalline cellulose about 0.6～0.9
Part, about 0.8～1.1 part of sodium carboxymethylcellulose, about 0.9～1.2 part of lactose, about 0.09～0.11 part of magnesium stearate, poly- second
About 0.9～1.3 part of glycol 4000, about 0.8～1.0 part of Hydroxypropyl methylcellulose, the ethanol solution that volume fraction is 50%～70%
About 7～10 parts, about 2～5 parts of sucrose, about 0.03～0.05 part of ethylmaltol；Take levo-oxiracetam, mannitol, micro-
Crystalline cellulose, sodium carboxymethylcellulose, lactose, sucrose, ethylmaltol are placed in Universalpulverizer, crush 100
It is placed in after mesh sieve in wet granulator, adds adhesive, start granulator (installing 24 mesh nylon mesh), starts granulation；
Obtained wet granular is put in air dry oven, setting temperature 50 C～60 DEG C drying time is 120min～150min,
So that particle water content≤3% (weight/mass percentage composition)；Coating material is taken, is added water and is made quality volume fraction for 6%～9%
Coating solution, it is standby；Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40～50
℃；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity, atomization is set
Pressure is 0.8～1.0bar, continues air intake and is dried, and solution stops heating, cooling after continuing to heat 10～15 minutes after having sprayed
Discharging, obtains final product coated granule.
3. the preparation method of the levo-oxiracetam particle of a kind of good stability as claimed in claim 1 or 2, its feature
It is that it is obtained as follows：
A. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, filler, flavouring, disintegrant and be placed in omnipotent powder
In broken machine, 100 mesh sieves were crushed, it is standby；
B. pelletize：Gained mixed-powder after pre-treatment is taken, in being placed in wet granulator, adhesive is added, starts granulator
(installing 24 mesh nylon mesh), starts granulation；
C. it is dried：It is by temperature 50 C～60 DEG C drying time in wet granular input air dry oven, is arranged
120min～150min so that particle water content≤3% (weight/mass percentage composition)；
D. coating：
The configuration of D (1) coating solution：The coating material of recipe quantity is taken, add water the coating for making that quality volume fraction is 6%～9%
Liquid, it is standby；
D (2) coating process：Above-mentioned dry particl is put in fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is
40～50 DEG C；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, 50～60rpm of spouting velocity is set,
Atomizing pressure is 0.8～1.0bar, continues air intake and is dried, and solution stops heating after continuing to heat 10～15 minutes after having sprayed,
Cooling discharging, obtains final product coated granule；
E. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, is sieved whole grain with 24 mesh nylon mesh, control environment
Below 25 DEG C of temperature, relative humidity is below 50%；
F. always mix：Lubricant was crushed into 100 mesh sieves, in adding the particle after whole grain, was mixed with three-dimensional motion mixer
10min～20min；
G. interior bag：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control,
Below relative humidity 50%, obtain final product.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109692167A (en) * | 2017-10-23 | 2019-04-30 | 重庆润泽医药有限公司 | The pharmaceutical composition and preparation method thereof for treating cognition dysfunction |
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| CN101288648A (en) * | 2008-06-16 | 2008-10-22 | 石药集团欧意药业有限公司 | Easy-to-administrate oxiracetam granular formulation and preparation method |
| 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 |
| CN102579386A (en) * | 2012-03-19 | 2012-07-18 | 北京德众万全药物技术开发有限公司 | Stable oxiracetam preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109692167A (en) * | 2017-10-23 | 2019-04-30 | 重庆润泽医药有限公司 | The pharmaceutical composition and preparation method thereof for treating cognition dysfunction |
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