CN107510664A - A kind of levo-oxiracetam particle and preparation method thereof - Google Patents
A kind of levo-oxiracetam particle and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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Abstract
A kind of levo-oxiracetam particle, it is characterised in that it is made by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 0.5 ~ 1.0 part of L cysteines, 0.7 ~ 1.3 part of mannitol, 0.5 ~ 1.2 part of microcrystalline cellulose, 1.0 ~ 1.5 parts of sodium carboxymethylcellulose, 1.1 ~ 1.5 parts of lactose, 0.12 ~ 0.16 part of talcum powder, 0.6 ~ 1.2 part of Macrogol 4000,0.7 ~ 1.3 part of hydroxypropyl methylcellulose, 8 ~ 15 parts of the starch slurry that quality volume fraction is 6% ~ 8%；It is smaller according to levo-oxiracetam particulate production impurity incrementss produced by the present invention, its increments is only 0.03%, product bisque amount is few, grain diameter is homogeneous, good fluidity, and not sub- angle is less than 37 °, content uniformity is less than 5%, it is good to store process stability, product is not easy moisture absorption caking, and shelf life is up to 24 months.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of levo-oxiracetam particle and preparation method thereof.
Background technology
Oxiracetam (oxiracetam, CAS No.：62613-82-5) the entitled Esomeprazole of chemistry,
The anti anoxia class cereboactive drug (compound is disclosed in US4118396) synthesized first in 1974 for Italian ISFS.P.A companies,
It is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promotes brain metabolism, it is right through blood-brain barrier
Specific nervous centralis road has stimulation, can improve intelligence and memory, to cerebrovascular disease, brain trauma, brain tumor, encephalic
Infection, brain degenerative disease etc. also have the effect of preferable, and the drug toxicity is extremely low, no mutagenesis and carcinogenesis and reproduction
Toxicity.Giorgio et al. discloses the chemical constitution and preparation method, Chiodini et al. of Oxiracetam in US4118396
Disclosed in WO9306826A, it is (right that clinical effectiveness proves that the drug effect of the Oxiracetam of S configurations (left-handed) is better than R configurations
Rotation), Oxiracetam and levo-oxiracetam structure are as follows.
Existing Oxiracetam particle is primarily present in preparation process that impurity increase is larger, particle bisque is more, and particle diameter is difficult to control, storage
It is poor to deposit process stability, particle hygroscopicity is strong, connecting block easy to stick, the technical problems such as shelf life is short.
The content of the invention
It is an object of the invention to provide the good levo-oxiracetam particle of a kind of size tunable, stability.
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：
The good levo-oxiracetam particle of a kind of stability, it is characterised in that it is using levo-oxiracetam as raw material, is added
A certain amount of filler, flavouring, adhesive, lubricant, coating material are made；Wherein described filler be starch, lactose,
One in dextrin, Icing Sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose, glucose, sodium carboxymethylcellulose, Cys
Kind is a variety of；The flavouring is sweet sucrose, maltose, ethylmaltol, Sucralose, stevia rebaudianum, sorbierite, mannitol, grape
One or more in sugar, aspartame；Described adhesive is water, ethanol, sucrose, starch slurry, dextrin, carboxymethyl cellulose, poly-
One or more in vinylpyrrolidone；The lubricant be talcum powder, magnesium stearate, polyethylene glycol, stearic acid, calcium stearate,
One or more in lauryl sodium sulfate, superfine silica gel powder, magnesia, paraffin；The coating material is Macrogol 4000, poly- second
In glycol 6000, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene acetaldehyde diethyl ester, hydroxypropyl methyl cellulose phthalate
It is one or more.
Inventor has found that specific supplementary product kind coordinates specific prescription consumption proportion relation in research process, then coordinate it is special
Preparation method, it may be such that impurity incrementss are smaller in above-mentioned levo-oxiracetam particulate production, product is not easy moisture absorption, is not easy
Adhesion caking, grain diameter are uniform, and content uniformity is small, and product stability is good, shelf life length；Above-mentioned levo-oxiracetam particle,
Characterized in that, it is made according to the following steps by the supplementary material of following weight proportion：1 part of levo-oxiracetam, the Guang ammonia of L- half
0.5~1.0 part of acid, 0.7~1.3 part of mannitol, 0.5~1.2 part of microcrystalline cellulose, 1.0~1.5 parts of sodium carboxymethylcellulose, lactose
1.1~1.5 parts, 0.12~0.16 part of talcum powder, 0.6~1.2 part of Macrogol 4000,0.7~1.3 part of hydroxypropyl methylcellulose, quality
Volume fraction is 6%~8% 8~15 parts of starch slurry；Take the levo-oxiracetam of recipe quantity, Cys, mannitol, micro-
Crystalline cellulose, sodium carboxymethylcellulose, lactose are placed in Universalpulverizer, after crushed 100 mesh sieves, are placed in wet granulator
In, the starch slurry that mass fraction is 6%~8% is added, starts granulator (18 mesh nylon mesh of installation), starts to pelletize；By wet
In grain input fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying, and drying time is 50~55 minutes；Take recipe quantity
Macrogol 4000, hydroxypropyl methylcellulose, add water be made quality volume fraction be 8%~10% coating solution, it is standby；Will be upper
State in dry particl input fluid bed, be passed through hot-air, be allowed to suspension fluidization, bed temperature is 40~50 DEG C；Coating solution is passed through into fluidisation
The nozzle atomization of bed is continuously added to fluid bed, sets 50~60rpm of spouting velocity, and atomizing pressure is 0.8~1.0bar, continues air intake
Dry, solution stops heating, cooling discharging after continuing heating after having sprayed 10~15 minutes；Coated granule is placed in crushing and pelletizing machine
In, with 20 mesh sieve whole grains；The talcum powder of recipe quantity be crushed into 100 mesh sieves, added in the particle after whole grain, with three-dimensional
Movement mixer mixing 10min~20min is produced.
In order to further improve the stability of levo-oxiracetam particle, Shelf-life, a kind of levo-oxiracetam particle, its
It is characterised by, it is made by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 0.7~0.9 part of Cys,
0.9~1.2 part of mannitol, 0.7~1.0 part of microcrystalline cellulose, 1.1~1.3 parts of sodium carboxymethylcellulose, 1.2~1.4 parts of lactose, cunning
0.13~0.15 part of stone flour, 0.7~1.1 part of Macrogol 4000,0.8~1.2 part of hydroxypropyl methylcellulose, quality volume fraction are 6%~8%
10~13 parts of starch slurry；Take levo-oxiracetam, Cys, mannitol, microcrystalline cellulose, the carboxymethyl of recipe quantity
Sodium cellulosate, lactose are placed in Universalpulverizer, after crushed 100 mesh sieves, are placed in wet granulator, add mass fraction
For 6%~8% starch slurry, start granulator (18 mesh nylon mesh of installation), start to pelletize；Wet granular is put into fluid bed,
Hotbed temperature sets 50 DEG C~70 DEG C, starts drying, and drying time is 50~55 minutes；Take recipe quantity Macrogol 4000,
Hydroxypropyl methylcellulose, add water that the coating solution that quality volume fraction is 8%~10% is made, it is standby；Above-mentioned dry particl is put into and fluidized
In bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature is 40~50 DEG C；Coating solution is continuous by the nozzle atomization of fluid bed
Fluid bed is added, sets 50~60rpm of spouting velocity, atomizing pressure is 0.8~1.0bar, continues air intake and dries, after solution has sprayed
Stop heating, cooling discharging after continuing heating 10~15 minutes；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieves
Whole grain；The talcum powder of recipe quantity be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion mixer
10min~20min is produced.
A kind of preparation method of levo-oxiracetam particle, it is characterised in that it is obtained as follows：
1. supplementary material pre-treatment：Take the levo-oxiracetam, filler, flavouring of recipe quantity to be placed in Universalpulverizer, crush
100 mesh sieves are crossed, it is standby；
2. granulation：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adds adhesive, starts granulator (installation
18 mesh nylon mesh), start to pelletize；
3. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Particle boiling is observed at any time
Situation, air blast situation are risen, prevents the particle-bonded ceramic the bottom of a pan, causes particle coking or gelatinization, drying time is 50~55 minutes, is protected
Demonstrate,prove pellet moisture≤3%；
4. coating：
(1) configuration of coating solution：The coating material of recipe quantity is taken, adds water that the solution that quality volume fraction is 8%~10% is made, it is standby
With；
(2) coating process：Above-mentioned dry particl is put into fluid bed, is passed through hot-air, is allowed to suspension fluidization, bed temperature is 40~50
℃；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50~60rpm of spouting velocity, atomizing pressure is
0.8~1.0bar, continue air intake and dry, solution stops heating after continuing heating after having sprayed 10~15 minutes, cooling discharging, produces bag
Clothing particle；
5. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, 25 DEG C of control environment temperature with
Under, relative humidity is below 50%；
It is 6. total mixed：Lubricant be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion mixer
10min~20min；
Wrapped in 7.：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature, relatively
Below humidity 50%, produce.
The present invention has following beneficial effect：
Levo-oxiracetam particulate production impurity incrementss of the present invention are smaller, and its increments is only 0.03%, product bisque amount
Few, grain diameter is homogeneous, good fluidity, and not sub- angle is less than 37 °, and content uniformity is less than 5%, and storage process stability is good, production
Product are not easy moisture absorption caking, and shelf life is up to 24 months, preparation technology simple possible, is worth marketing.
Embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be following examples be served only for this
Invention is further described, it is impossible to limiting the scope of the invention is interpreted as, without departing substantially from spirit of the invention and essence
In the case of, the modifications or substitutions made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：
1. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, Cys, mannitol, microcrystalline cellulose, carboxylic first
Base sodium cellulosate, lactose are placed in Universalpulverizer, crushed 100 mesh sieves, standby；
2. granulation：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adds the starch slurry that mass fraction is 6%,
Start granulator (18 mesh nylon mesh of installation), start to pelletize；
3. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Particle boiling is observed at any time
Situation, air blast situation are risen, prevents the particle-bonded ceramic the bottom of a pan, causes particle coking or gelatinization, drying time is 50~55 minutes, is protected
Demonstrate,prove pellet moisture≤3%；
4. coating：
(1) configuration of coating solution：Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity are taken, adds water that quality volume fraction is made to be
8%~10% solution, it is standby；
(2) coating process：Above-mentioned dry particl is put into fluid bed, is passed through hot-air, is allowed to suspension fluidization, bed temperature is 40~50
℃；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50~60rpm of spouting velocity, atomizing pressure is
0.8~1.0bar, continue air intake and dry, solution stops heating after continuing heating after having sprayed 10~15 minutes, cooling discharging, produces bag
Clothing particle；
5. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, 25 DEG C of control environment temperature with
Under, relative humidity is below 50%；
It is 6. total mixed：Talcum powder be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion mixer
10min~20min；
Wrapped in 7.：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature, relatively
Below humidity 50%, produce.
Experiment one：Particle stops sub- angle measure
1. test material：Sample after the completion of always being mixed in the preparation process of embodiment 1
2. test method：After the completion of embodiment 1 is always mixed, respectively in the upper, middle and lower of three-dimensional motion mixer, left and right each point
Separately sampled measure angle of repose, judges its mobility；
3. result of the test：
4. conclusion (of pressure testing)：It can be seen that by upper table result of the test, five times measurement angle of repose is respectively less than 36 °, shows that mobility of particle is good.
Experiment two：Content uniformity
1. test material：10 bags of particulate samples made from Example 1, shine《Chinese Pharmacopoeia》Two annex of version in 2010
Content uniformity inspection under granula item.
2. determination method：The weight of 10 bags of test sample, respectively weighed every bag of content is taken, every bag of weight is compared with sign loading amount.
3. result of the test：Content uniformity inspection result see the table below：
4. conclusion (of pressure testing)：This product content uniformity is respectively less than ± 4% it can be seen from upper table result of the test, it was demonstrated that and content uniformity is stable,
Content uniformity is small.
Experiment three：A kind of levo-oxiracetam particle prescription of the present invention is on the increased influence of preparation process impurity
1. experiment material：
Levo-oxiracetam particulate samples：Prepared by embodiment 1.
Levo-oxiracetam control sample：To lack the sample obtained by Cys on the basis of the prescription of embodiment 1, its
Preparation technology is the same as embodiment 1.
2. experimental method：In the preparation process of embodiment 1, levo-oxiracetam bulk drug and levo-oxiracetam particle are determined respectively
The relevant material of finished product, observation levo-oxiracetam particle impurity in preparation process increase situation.Meanwhile take and lack the Guangs of L- half
The prescription of the embodiment 1 of propylhomoserin is prepared by the preparation method of embodiment 1 as control prescription, equally determines left-handed Aura respectively
The relevant material of western smooth bulk drug and levo-oxiracetam finished granule, observe levo-oxiracetam particle impurity in preparation process
Increase situation.
3. experimental result see the table below：
4. experiment conclusion：The prescription of embodiment 1, coordinate specific preparation method, relevant material increase is only 0.03%, hence it is evident that excellent
In control sample.
Experiment four：A kind of levo-oxiracetam granule stability experiment of the present invention
Experiment material：
Levo-oxiracetam particle：It is made for embodiment 1.
Acceleration study method：Levo-oxiracetam particle made from embodiment 1 is packed by listing, put in Acceleration study case, one
Fix time sampling, investigation project is tested.
Acceleration study temperature：40±2℃
Acceleration study humidity：RH75% ± 5%
Investigate the time：0th, 1,2,3, June
Inspection target：Character, moisture, granularity, melting, relevant material, content, microbial limit
Accelerated test stability records：
Acceleration study result shows：Acceleration sample in June is suitable with 0 month sample items Testing index quality, and it is real to show that this product accelerates
Test June, quality keeps stable, and this product stability is preferable.
Long-term experiment method：Levo-oxiracetam particle made from embodiment 1 is packed by listing, put in the long-term case that keeps sample, one
Fix time sampling, investigation project is tested.
Long-term experiment temperature：25±2℃
Long-term experiment humidity：RH60% ± 10%
Investigate the time：0th, 3,6,9,12,18,24 months
Inspection target：Character, moisture, granularity, melting, relevant material, content, microbial limit
Long term test stability records：
Long term test shows：It is 24 months characters of this product long term test, moisture, granularity, melting, relevant material, content, micro-
Biological limit meets every relevant regulations of production quality standard draft without significant changes.This product long term test 24 months
Steady quality, therefore minimum 24 months of this product term of validity, long term test is still during investigation is continued.
Embodiment 2
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Tested by the test method of embodiment 1, not sub- angle experiment
Measurement result shows that this product mobility of particle is good, and not sub- angle is less than 37 °, and content uniformity experiment shows that this product content uniformity is less than 5%,
This product loading amount is stable, controllable, and stability test result shows that acceleration sample quality in June is stable, long-term 24 months steady qualities,
Therefore this product term of validity at least 24 months, the product prescription result of the test that influences increased on preparation process impurity show this product preparation process
Impurity incrementss are smaller, and relevant material only increases by 0.02% in preparation process.
Embodiment 3
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Tested by the test method of embodiment 1, not sub- angle experiment
Measurement result shows that this product mobility of particle is good, and not sub- angle is less than 35 °, and content uniformity experiment shows that this product content uniformity is less than 4%,
This product loading amount is stable, controllable, and stability test result shows that acceleration sample quality in June is stable, long-term 24 months steady qualities,
Therefore this product term of validity at least 24 months, the product prescription result of the test that influences increased on preparation process impurity show this product preparation process
Impurity incrementss are smaller, and relevant material only increases by 0.03% in preparation process.
Embodiment 4-6：A kind of levo-oxiracetam particle, is prepared by the supplementary material of following weight, the same embodiment of preparation method
1：
| Embodiment | 4 | 5 | 6 |
| Levo-oxiracetam | 1 part | 1 part | 1 part |
| Cys | 0.9 part | 0.8 part | 0.7 part |
| Mannitol | 1.0 part | 1.1 part | 1.0 part |
| Microcrystalline cellulose | 0.9 part | 0.8 part | 0.9 part |
| Sodium carboxymethylcellulose | 1.1 part | 1.2 part | 1.3 part |
| Lactose | 1.4 part | 1.3 part | 1.2 part |
| Talcum powder | 0.13 part | 0.14 part | 0.15 part |
| Macrogol 4000 | 1.0 part | 0.9 part | 0.8 part |
| Hydroxypropyl methylcellulose | 0.9 part | 1.0 part | 1.1 part |
| Mass fraction is 7% starch slurry | 11 parts | 12 parts | 12 parts |
Preparation process：It is made according to the preparation technology of embodiment 1.Sample obtained by embodiment 4,5,6 presses the examination of embodiment 1
Proved recipe method is tested, and the product of embodiment 4,5,6 stops sub- angle experiment measurement result and shows that this product mobility of particle is good, not sub- angle
Respectively lower than 37 °, 36 °, 36 °, content uniformity experiment shows that the product content uniformity of embodiment 4,5,6 is respectively less than 5%,
This product loading amount is stable, controllable, and the stability test result of embodiment 4,5,6 shows to accelerate sample quality in June stable, for a long time
24 months quality are stable, therefore this product term of validity at least 24 months, and the product prescription of embodiment 4,5,6 is to preparation process impurity
Increased influence result of the test shows that this product preparation process impurity incrementss are smaller, there is the sample of embodiment 4,5,6 in preparation process
Close material only increases by 0.03%, 0.02%, 0.03% respectively.
Claims (3)
1. a kind of levo-oxiracetam particle, it is characterised in that it is made according to the following steps by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 0.5 ~ 1.0 part of Cys, 0.7 ~ 1.3 part of mannitol, 0.5 ~ 1.2 part of microcrystalline cellulose, 1.0 ~ 1.5 parts of sodium carboxymethylcellulose, 1.1 ~ 1.5 parts of lactose, 0.12 ~ 0.16 part of talcum powder, 0.6 ~ 1.2 part of Macrogol 4000,0.7 ~ 1.3 part of hydroxypropyl methylcellulose, 8 ~ 15 parts of the starch slurry that quality volume fraction is 6% ~ 8%；Levo-oxiracetam, Cys, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, the lactose of recipe quantity is taken to be placed in Universalpulverizer; after crushed 100 mesh sieves; it is placed in wet granulator, adds the starch slurry that mass fraction is 6% ~ 8%, start granulator（18 mesh nylon mesh are installed）, start to pelletize；Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C ~ 70 DEG C, starts drying, and drying time is 50 ~ 55 minutes；Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity are taken, adds water that the coating solution that quality volume fraction is 8% ~ 10% is made, it is standby；Above-mentioned dry particl is put into fluid bed, is passed through hot-air, is allowed to suspension fluidization, bed temperature is 40 ~ 50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50 ~ 60rpm of spouting velocity, atomizing pressure is 0.8 ~ 1.0bar, continues air intake and dries, and solution stops heating, cooling discharging after continuing heating after having sprayed 10 ~ 15 minutes；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；The talcum powder of recipe quantity be crushed into 100 mesh sieves, add in the particle after whole grain, produced with three-dimensional motion mixer mixing 10min ~ 20min.
2. a kind of levo-oxiracetam particle as claimed in claim 1, it is characterised in that it is made according to the following steps by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 0.7 ~ 0.9 part of Cys, 0.9 ~ 1.2 part of mannitol, 0.7 ~ 1.0 part of microcrystalline cellulose, 1.1 ~ 1.3 parts of sodium carboxymethylcellulose, 1.2 ~ 1.4 parts of lactose, 0.13 ~ 0.15 part of talcum powder, 0.7 ~ 1.1 part of Macrogol 4000,0.8 ~ 1.2 part of hydroxypropyl methylcellulose, 10 ~ 13 parts of the starch slurry that quality volume fraction is 6% ~ 8%；Levo-oxiracetam, Cys, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, the lactose of recipe quantity is taken to be placed in Universalpulverizer; after crushed 100 mesh sieves; it is placed in wet granulator, adds the starch slurry that mass fraction is 6% ~ 8%, start granulator（18 mesh nylon mesh are installed）, start to pelletize；Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C ~ 70 DEG C, starts drying, and drying time is 50 ~ 55 minutes；Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity are taken, adds water that the coating solution that quality volume fraction is 8% ~ 10% is made, it is standby；Above-mentioned dry particl is put into fluid bed, is passed through hot-air, is allowed to suspension fluidization, bed temperature is 40 ~ 50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50 ~ 60rpm of spouting velocity, atomizing pressure is 0.8 ~ 1.0bar, continues air intake and dries, and solution stops heating, cooling discharging after continuing heating after having sprayed 10 ~ 15 minutes；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；The talcum powder of recipe quantity be crushed into 100 mesh sieves, add in the particle after whole grain, produced with three-dimensional motion mixer mixing 10min ~ 20min.
3. the preparation method of levo-oxiracetam particle as claimed in claim 1 or 2, it is characterised in that it is obtained as follows：
A. supplementary material pre-treatment：Take the levo-oxiracetam, filler, flavouring of recipe quantity to be placed in Universalpulverizer, crushed 100 mesh sieves, it is standby；
B. pelletize：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adds adhesive, starts granulator（18 mesh nylon mesh are installed）, start to pelletize；
C. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C ~ 70 DEG C, starts drying；Particle boiling situation, air blast situation are observed at any time, prevents the particle-bonded ceramic the bottom of a pan, causes particle coking or gelatinization, and drying time is 50 ~ 55 minutes, ensures pellet moisture≤3%；
D. it is coated：
The configuration of D (1) coating solutions：The coating material of recipe quantity is taken, adds water that the solution that quality volume fraction is 8% ~ 10% is made, it is standby；
D (2) coating process：Above-mentioned dry particl is put into fluid bed, is passed through hot-air, is allowed to suspension fluidization, bed temperature is 40 ~ 50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50 ~ 60rpm of spouting velocity, atomizing pressure is 0.8 ~ 1.0bar, continues air intake and dries, and solution stops heating after continuing heating after having sprayed 10 ~ 15 minutes, cooling discharging, produces coated granule；
E. whole grain, sub-sieve:Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, controlled below 25 DEG C of environment temperature, relative humidity is below 50%；
F. it is total mixed：Lubricant be crushed into 100 mesh sieves, added in the particle after whole grain, with three-dimensional motion mixer mixing 10min ~ 20min；
G. interior bag：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature, relative humidity produces below 50%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610424868.3A CN107510664B (en) | 2016-06-15 | 2016-06-15 | Levo-oxiracetam particle and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610424868.3A CN107510664B (en) | 2016-06-15 | 2016-06-15 | Levo-oxiracetam particle and preparation method thereof |
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| Publication Number | Publication Date |
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| CN107510664A true CN107510664A (en) | 2017-12-26 |
| CN107510664B CN107510664B (en) | 2020-09-01 |
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| CN113412925A (en) * | 2021-07-02 | 2021-09-21 | 福建泉州味中皇食品有限公司 | Bagged food powder not prone to caking and production equipment thereof |
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| 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 |
| CN103599083A (en) * | 2013-12-06 | 2014-02-26 | 重庆东泽医药科技发展有限公司 | Levo-oxiracetam slow-release tablet and preparation method thereof |
| CN104739796A (en) * | 2013-12-27 | 2015-07-01 | 重庆东泽医药科技发展有限公司 | An oxiracetam tablet and a preparing method thereof |
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| 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 |
| CN103599083A (en) * | 2013-12-06 | 2014-02-26 | 重庆东泽医药科技发展有限公司 | Levo-oxiracetam slow-release tablet and preparation method thereof |
| CN104739796A (en) * | 2013-12-27 | 2015-07-01 | 重庆东泽医药科技发展有限公司 | An oxiracetam tablet and a preparing method thereof |
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| CN113412925A (en) * | 2021-07-02 | 2021-09-21 | 福建泉州味中皇食品有限公司 | Bagged food powder not prone to caking and production equipment thereof |
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