CN106606484A - L-oxiracetam particles with high dissolution and dispersion speed and preparation method thereof - Google Patents
L-oxiracetam particles with high dissolution and dispersion speed and preparation method thereof Download PDFInfo
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- CN106606484A CN106606484A CN201510705259.0A CN201510705259A CN106606484A CN 106606484 A CN106606484 A CN 106606484A CN 201510705259 A CN201510705259 A CN 201510705259A CN 106606484 A CN106606484 A CN 106606484A
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Abstract
The invention discloses L-oxiracetam particles with high dissolution and dispersion speed. The L-oxiracetam particles are characterized by being prepared from the following raw and auxiliary materials in parts by weight: about 1 part of L-oxiracetam, about 0.8-1.3 parts of mannitol, about 1.0-1.5 parts of microcrystalline cellulose, about 0.9-1.5 parts of sodium carboxymethylcellulose, about 1.1-1.5 parts of lactose, about 0.05-0.10 parts of talcum powder, about 0.7-1.5 parts of polyethylene glycol 4000, about 0.3-0.8 parts of hydroxypropyl methylcellulose, about 0.5-1.0 part of low-substituted hydroxypropyl cellulose, about 0.05-0.1 parts of polysorbate 80, and about 6-10 parts of 6-8% by weight of starch slurry. The L-oxiracetam particles prepared according to a method is small in powder layer quantity, uniform in particle size, good in flowability, and high in dissolution and dispersion speed; a wart angle is smaller than 33 degrees, the load difference is lower than 5%, and the dissolution and dispersion time of all the particles does not exceed 30 seconds; a storage process is high in stability; a product difficultly absorbs moisture to be caked, and the shelf life of the product is long and reaches 36 months; and a preparation process is simple and feasible, and is worthy of popularization.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to one kind leach fireballing levo-oxiracetam granule and its
Preparation method.
Background technology
Nootropics are that a kind of promotion learns also known as cereboactive drug, the new medicine for central nervous system of memory reinforcing.Promote
Intelligence medicine requires selection in cerebral cortex, with selection activation, protection and promotion damaged nerve cell functional rehabilitation
Feature.Different from other neurologic agents be a little their above-mentioned effect not by reticular system or olfactory bulb, but directly
Connect and act on cortex.Behavior is affected neither, also without calm excitation, therefore such medicine has caused the extensive pass of people
Note and interest, also grow with each passing day to the demand of such medicine.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) chemical entitled 4- hydroxyls -2- oxo -1- pyrroles
Alkyl acetamide, is that (compound is draped over one's shoulders the anti-hypoxia class nootropics that synthesized in 1974 first of Italian ISFS.P.A companies
It is exposed to US4118396), it is ring GABOB derivants, Phosphorylcholine and phosphatidyl ethanolamine synthesis can be promoted, promote brain generation
Thank, through blood brain barrier, have stimulation to specificity nervus centraliss road, intelligence and memory can be improved, to brain blood
Pipe disease, cerebral trauma, cerebroma, intracranial infection, brain degenerative disease etc. also have preferable curative effect, and the drug toxicity pole
It is low, without mutagenesis and carcinogenesis and genotoxicity.Giorgio et al. discloses oxiracetam in US4118396
Chemical constitution and preparation method, Chiodini et al. are disclosed in WO9306826A, and clinical effectiveness proves that S configurations are (left
Rotation) the drug effect of oxiracetam be better than R configurations (dextrorotation), oxiracetam and levo-oxiracetam structure are as follows.
Existing oxiracetam granule is primarily present that preparation process granule bisque is more, and particle diameter is wayward, stores process stabilization
Property it is poor, granule hygroscopicity is strong, and connecting block easy to stick, shelf life are short, and granule leaches the technical problems such as speed is slow.
The content of the invention
It is an object of the invention to provide a kind of size tunable, good stability, leaching fireballing levo-oxiracetam granule.
Another object of the present invention is to provide the preparation method of above-mentioned levo-oxiracetam granule.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam granule, it is, with levo-oxiracetam as raw material, to add a certain amount of filler, rectify
Taste agent, binding agent, lubricant, disintegrating agent, 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 carboxymethyl cellulose；It is described
Correctivess are sucrose, maltose, ethylmaltol, sucralose, sweet Flos Chrysanthemi, Sorbitol, Mannitol, glucose, A Si
One or more during handkerchief is smooth；Described adhesive is water, ethanol, sucrose, starch slurry, dextrin, carboxymethyl cellulose, poly- second
One or more in alkene pyrrolidone；The lubricant is Pulvis Talci, magnesium stearate, Polyethylene Glycol, stearic acid, stearic acid
Calcium, sodium lauryl sulphate, micropowder silica gel, magnesium oxide, one or more in paraffin；The disintegrating agent is low-substituted hydroxypropyl
One or more in base cellulose, polyoxyethylene sorbitan monoleate, carboxymethyl starch sodium, dried starch；The coating material is poly- second two
Alcohol 4000, polyethylene glycol 6000, hydroxypropyl cellulose, hypromellose, AEA, hydroxypropyl first
One or more in base cellulose phthalate.
The rational prescription proportioning of inventor, coordinates specific preparation method, above-mentioned levo-oxiracetam grain diameter can be caused uniformly may be used
Control, storage process is difficult moisture absorption, is difficult that adhesion caking, product stability are good, and shelf life is long, and it is fast that granule leaches speed；
Above-mentioned levo-oxiracetam granule, it is characterised in that it is obtained by the supplementary material of following weight proportion：Left-handed Aura west
Smooth 1 part, 0.8～1.3 part of Mannitol, 1.0～1.5 parts of Microcrystalline Cellulose, 0.9～1.5 part of sodium carboxymethyl cellulose, Lactose
1.1～1.5 parts, 0.05～0.10 part of Pulvis Talci, 0.7～1.5 part of Macrogol 4000,0.3～0.8 part of hypromellose,
0.5～1.0 part of low-substituted hydroxypropyl cellulose, 0.05～0.1 part of polyoxyethylene sorbitan monoleate, the starch slurry that mass fraction is 6%～8%
6～10 parts；Take the levo-oxiracetam of recipe quantity, Mannitol, Microcrystalline Cellulose, sodium carboxymethyl cellulose, Lactose, low
Replace hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate to be placed in Universalpulverizer, crushed 100 mesh sieves, and be placed in wet granulation
In machine, the starch slurry that mass fraction is 6%～8% is added, start granulator (installing 18 mesh nylon mesh), start granulation；
Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, start drying, drying time is 50～55 minutes；
Macrogol 4000, the hypromellose of recipe quantity are taken, add water the coating solution for making that quality volume fraction is 8%～10%,
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；Will
Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50～60rpm of spouting velocity, and atomizing pressure is
0.8～1.0bar, continues air intake and is dried, 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 granulate；The Pulvis Talci of recipe quantity was crushed into 100 mesh
Sieve, in adding the granule after granulate, is obtained final product with three-dimensional motion mixer mixing 10min～20min.
Further, in order to further speed up the speed that leaches of levo-oxiracetam granule, stability is improved, extends shelf
Phase, a kind of levo-oxiracetam granule, it is characterised in that it is obtained by the supplementary material of following weight proportion：Left-handed Austria
1 part of La Xitan, 0.9～1.1 part of Mannitol, 1.1～1.3 parts of Microcrystalline Cellulose, 1.1～1.3 parts of sodium carboxymethyl cellulose,
1.2～1.4 parts of Lactose, 0.06～0.09 part of Pulvis Talci, 0.9～1.2 part of Macrogol 4000, hypromellose 0.5～0.7
Part, 0.6～0.9 part of low-substituted hydroxypropyl cellulose, 0.07～0.09 part of polyoxyethylene sorbitan monoleate, mass fraction are 6%～8%
6～10 parts of starch slurry；Take the levo-oxiracetam of recipe quantity, Mannitol, Microcrystalline Cellulose, sodium carboxymethyl cellulose,
Lactose, low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate are placed in Universalpulverizer, are crushed 100 mesh sieves, and are placed in
In wet granulator, the starch slurry that mass fraction is 6%～8% is added, starts granulator (installing 18 mesh nylon mesh),
Start granulation；Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, starts drying, and drying time is
50～55 minutes；Macrogol 4000, the hypromellose of recipe quantity are taken, is added water and is made quality volume fraction and be
8%～10% coating solution, it is standby；Above-mentioned dry particl is put in fluid bed, hot-air is passed through, is allowed to suspension fluidization,
Bed temperature is 40～50 DEG C；Coating solution is continuously added to into fluid bed by the nozzle atomization of fluid bed, spouting velocity is set
50～60rpm, atomizing pressure are 0.8～1.0bar, continue air intake and are dried, after solution continues heating 10～15 minutes after having sprayed
Stop heating, cooling discharging；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve granulate；By recipe quantity
Pulvis Talci crushed 100 mesh sieves, in adding the granule after granulate, with three-dimensional motion mixer mixing 10min～20min
Obtain final product.
A kind of preparation method for leaching fireballing levo-oxiracetam granule, it is characterised in that it is to make as follows
：
1. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, filler, correctivess, disintegrating agent 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, is placed in wet granulator, is added binding agent, start granulator
(installing 18 mesh nylon mesh), starts granulation；
3. it is dried：Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, starts drying；Observe at any time
Granule boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause granule coking or gelatinizing, and drying time is 50～55
Minute, it is ensured that pellet moisture≤3%；
4. coating：
(1) preparation of coating solution：The coating material of recipe quantity is taken, add water the coating solution for making that mass fraction is 8%～10%,
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 heating after having sprayed 10～15 minutes
Discharging, obtains final product coated granule；
5. granulate, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve granulate, ambient temperature is controlled
Less than 25 DEG C, relative humidity is below 50%；
6. total mixed：Lubricant was crushed into 100 mesh sieves, in adding the granule after granulate, was mixed with three-dimensional motion mixer
10min～20min；
7. bag in：Packed with particles packing machine, packing specification is set as 1g/ bags, below 25 DEG C of ambient temperature of control,
Below relative humidity 50%, obtain final product.
The present invention has following beneficial effect：
Levo-oxiracetam granule bisque amount of the present invention is few, and grain diameter is homogeneous, good fluidity, and not sub- angle is less than 33 °,
Content uniformity is less than 5%, and granule leaches speed soon, and granule all leached the time not over 30 seconds, stores process stabilization
Property it is good, product be difficult the moisture absorption caking, shelf life be up to 36 months, preparation process is simple is feasible, and worth market pushes away
Extensively.
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
One kind leaches fireballing levo-oxiracetam granule, is obtained according to the following steps：
Preparation process：
1. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, Mannitol, Microcrystalline Cellulose, carboxymethyl cellulose
Sodium, Lactose, low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate are placed in Universalpulverizer, crush 100 mesh sieves,
It is standby；
2. pelletize：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, is added starch slurry, start granulator
(installing 18 mesh nylon mesh), starts granulation；
3. it is dried：Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, starts drying；Observe at any time
Granule boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause granule coking or gelatinizing, and drying time is 50～55
Minute, it is ensured that pellet moisture≤3%；
4. coating：
(1) preparation of coating solution：Macrogol 4000, the hypromellose of recipe quantity are taken, is added water and is made mass fraction and be
8%～10% coating solution, 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 heating after having sprayed 10～15 minutes
Discharging, obtains final product coated granule；
5. granulate, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve granulate, ambient temperature is controlled
Less than 25 DEG C, relative humidity is below 50%；
6. total mixed：Pulvis Talci was crushed into 100 mesh sieves, in adding the granule after granulate, was mixed with three-dimensional motion mixer
10min～20min；
7. bag in：Packed with particles packing machine, packing specification is set as 1g/ bags, below 25 DEG C of ambient temperature of control,
Below relative humidity 50%, obtain final product.
Test one：Granule is stopped sub- angle and is determined
1. test material：Sample after the completion of always mixing in 1 preparation process of embodiment
2. test method：Embodiment 1 it is total it is mixed after the completion of, respectively in upper, middle and lower of three-dimensional motion mixer, left and right
Each point separately sampled measure angle of repose, judge its mobility；
3. result of the test：
4. conclusion (of pressure testing)：Can be seen that by upper table result of the test, five measurements are respectively less than 33 ° angle of repose, show particle flow
Property is good.
Test two：Content uniformity
1. test material：10 bags of particulate samples obtained in Example 1, shine《Chinese Pharmacopoeia》Version two is attached within 2010
Content uniformity inspection under record granule item.
2. algoscopy：Take 10 bags of test sample, the weight of the weighed every bag of content of difference, per bag of weight and sign loading amount
Compare.
3. result of the test：Content uniformity inspection result see the table below：
4. conclusion (of pressure testing)：This product content uniformity can be seen that by upper table result of the test and be respectively less than ± 5%, it was demonstrated that content uniformity is steady
Fixed, content uniformity is little.
Test three：A kind of levo-oxiracetam granule stability experiment of the present invention
Experiment material：
Levo-oxiracetam granule：It is obtained for embodiment 1.
Acceleration study method：By levo-oxiracetam granule obtained in embodiment 1 by listing packaging, put in 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：Character, 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 keep stable, and this product stability is preferable.
Long-term experiment method：By levo-oxiracetam granule obtained in embodiment 1 by listing packaging, put,
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：Character, moisture, granularity, melting, relevant material, content, microbial limit
Long term test stability is recorded：
Long term test shows：36 months character 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 effect duration is minimum 36 months, long term test is still during continuing to investigate.
Test four：Dissolution test
1. test material：Levo-oxiracetam granule obtained in embodiment 1；
2. test method：10 bags of levo-oxiracetam granule obtained in Example 1, are placed in 100ml beakers, plus
Enter the purified water that 50ml temperature is 25 DEG C, static, observation all leaches the required time；
3. result of the test see the table below：
| Test number | 1# | 2# | 3# | 4# | 5# |
| Leach the time (min) | 25 seconds | 22 seconds | 21 seconds | 26 seconds | 23 seconds |
| Test number | 6# | 7# | 8# | 9# | 10# |
| Leach the time (min) | 27 seconds | 22 seconds | 23 seconds | 26 seconds | 26 seconds |
4. conclusion (of pressure testing)：Can be seen that by upper table result of the test, repeatedly measurement granule leaches the time less than 30 seconds, it was demonstrated that press
It is fast that granule obtained in of the invention leaches speed.
Embodiment 2
One kind leaches fireballing levo-oxiracetam granule, is obtained according to the following steps：
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, granule is carried out respectively and is stopped
Sub- angle measure, content uniformity inspection, sample stability are tested and leach timing, and measurement result table is tested at not sub- angle
Bright this product mobility of particle is good, and not sub- angle is less than 33 °, and content uniformity test shows this product content uniformity less than 5%, this
Product loading amount is stable, controllable, and dissolution test result shows that repeatedly determining this product leaches the time respectively less than 30 seconds, therefore this product energy
Leach rapidly, stability test result shows to accelerate June sample quality stable, long-term 36 months steady qualities, therefore this
At least 36 months product effect duration.
Embodiment 3
One kind leaches fireballing levo-oxiracetam granule, is obtained according to the following steps：
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, granule is carried out respectively and is stopped
Sub- angle measure, content uniformity inspection, sample stability are tested and leach timing, and measurement result table is tested at not sub- angle
Bright this product mobility of particle is good, and not sub- angle is less than 33 °, and content uniformity test shows this product content uniformity less than 5%, this
Product loading amount is stable, controllable, and dissolution test result shows that repeatedly determining this product leaches the time respectively less than 30 seconds, therefore this product energy
Leach rapidly, stability test result shows to accelerate June sample quality stable, long-term 36 months steady qualities, therefore this
At least 36 months product effect duration.
Embodiment 4-6：One kind leaches fireballing levo-oxiracetam granule, 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 | 1.1 part | 1.0 part | 0.9 part |
| Microcrystalline Cellulose | 1.1 part | 1.2 part | 1.3 part |
| Sodium carboxymethyl cellulose | 1.3 part | 1.2 part | 1.1 part |
| Lactose | 1.4 part | 1.3 part | 1.2 part |
| Pulvis Talci | 0.08 part | 0.07 part | 0.09 part |
| Macrogol 4000 | 1.1 part | 1.0 part | 0.9 part |
| Hypromellose | 0.5 part | 0.6 part | 0.7 part |
| Low-substituted hydroxypropyl cellulose | 0.9 part | 0.8 part | 0.7 part |
| Polyoxyethylene sorbitan monoleate | 0.07 part | 0.08 part | 0.09 part |
| Mass fraction is 6% starch slurry | 7 parts | 8 parts | 9 parts |
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, granule is carried out respectively and is stopped
Timing is tested and leached to sub- angle measure, content uniformity inspection, sample stability, and embodiment 4,5,6 stops sub- angle
Test measurement result shows that embodiment mobility of particle is good, and not sub- angle is less than 33 °, the examination of 4,5,6 content uniformity of embodiment
Test and show this product content uniformity less than 5%, this product loading amount is stable, controllable, 4,5,6 dissolution test result table of embodiment
Bright multiple measure this product leaches the time respectively less than 30 seconds, therefore this product can be leached rapidly, the examination of 4,5,6 stability of embodiment
Test result to show to accelerate June sample quality stable, long-term 36 months steady qualities, therefore at least 36 months this product effect duration.
Claims (3)
1. one kind leaches fireballing levo-oxiracetam granule, it is characterised in that it is by the supplementary material of following weight proportion
And following steps are obtained：1 part or so of levo-oxiracetam, 0.8～1.3 part or so of Mannitol, Microcrystalline Cellulose 1.0～1.5
Part or so, 0.9～1.5 part or so of sodium carboxymethyl cellulose, 1.1～1.5 parts or so of Lactose, 0.05～0.10 part of Pulvis Talci are left
The right side, 0.7～1.5 part or so of Macrogol 4000,0.3～0.8 part or so of hypromellose, low substituted hydroxy-propyl fiber
0.5～1.0 part or so of element, 0.05～0.1 part or so of polyoxyethylene sorbitan monoleate, 6～10 parts of the starch slurry that mass fraction is 6%～8%
Left and right；Take the levo-oxiracetam of recipe quantity, Mannitol, Microcrystalline Cellulose, sodium carboxymethyl cellulose, Lactose, low take
It is placed in Universalpulverizer for hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate, crushed 100 mesh sieves, and be placed in wet granulator
In, the starch slurry that mass fraction is 6%～8% is added, is started granulator (installing 18 mesh nylon mesh), is started granulation；
Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, start drying, drying time is 50～55 minutes；
Macrogol 4000, the hypromellose of recipe quantity are taken, add water the coating solution for making that quality volume fraction is 8%～10%,
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；Will
Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50～60rpm of spouting velocity, and atomizing pressure is
0.8～1.0bar, continues air intake and is dried, 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 granulate；The Pulvis Talci of recipe quantity was crushed into 100 mesh
Sieve, in adding the granule after granulate, is obtained final product with three-dimensional motion mixer mixing 10min～20min.
2. levo-oxiracetam granule as claimed in claim 1, it is characterised in that it is by the original of following weight proportion
Adjuvant and following steps are obtained：1 part or so of levo-oxiracetam, 0.9～1.1 part or so of Mannitol, Microcrystalline Cellulose 1.1～1.3
Part or so, 1.1～1.3 parts or so of sodium carboxymethyl cellulose, 1.2～1.4 parts or so of Lactose, 0.06～0.09 part of Pulvis Talci are left
The right side, 0.9～1.2 part or so of Macrogol 4000,0.5～0.7 part or so of hypromellose, low substituted hydroxy-propyl fiber
0.6～0.9 part or so of element, 0.07～0.09 part or so of polyoxyethylene sorbitan monoleate, the starch slurry 6～10 that mass fraction is 6%～8%
Part or so；Take the levo-oxiracetam of recipe quantity, Mannitol, Microcrystalline Cellulose, sodium carboxymethyl cellulose, Lactose, low
Replace hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate to be placed in Universalpulverizer, crushed 100 mesh sieves, and be placed in wet granulation
In machine, the starch slurry that mass fraction is 6%～8% is added, start granulator (installing 18 mesh nylon mesh), start granulation；
Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, start drying, drying time is 50～55 minutes；
Macrogol 4000, the hypromellose of recipe quantity are taken, add water the coating solution for making that quality volume fraction is 8%～10%,
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；Will
Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50～60rpm of spouting velocity, and atomizing pressure is
0.8～1.0bar, continues air intake and is dried, 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 granulate；The Pulvis Talci of recipe quantity was crushed into 100 mesh
Sieve, in adding the granule after granulate, is obtained final product with three-dimensional motion mixer mixing 10min～20min.
3. a kind of preparation method for leaching fireballing levo-oxiracetam granule as claimed in claim 1 or 2, which is special
Levy and be, it is obtained as follows：
A. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, filler, correctivess, disintegrating agent 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, is placed in wet granulator, is added binding agent, start granulator
(installing 18 mesh nylon mesh), starts granulation；
C. it is dried：Wet granular is put in fluid bed, hotbed temperature sets 50 DEG C～70 DEG C, starts drying；Observe at any time
Granule boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause granule coking or gelatinizing, and drying time is 50～55
Minute, it is ensured that pellet moisture≤3%；
D. coating：
The preparation of D (1) coating solution：The coating material of recipe quantity is taken, add water the coating solution for making that mass fraction is 8%～10%,
It is standby；
D (2) coating process：Above-mentioned dry particl is put in fluid bed, hot-air is passed through, is allowed to suspension fluidization, 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 heating after having sprayed 10～15 minutes,
Cooling discharging, obtains final product coated granule；
E. granulate, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve granulate, ambient temperature is controlled
Less than 25 DEG C, relative humidity is below 50%；
F. it is total mixed：Lubricant was crushed into 100 mesh sieves, in adding the granule after granulate, was mixed with three-dimensional motion mixer
10min～20min；
G. interior bag：Packed with particles packing machine, packing specification is set as 1g/ bags, below 25 DEG C of ambient temperature of control,
Below relative humidity 50%, obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510705259.0A CN106606484A (en) | 2015-10-27 | 2015-10-27 | L-oxiracetam particles with high dissolution and dispersion speed and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510705259.0A CN106606484A (en) | 2015-10-27 | 2015-10-27 | L-oxiracetam particles with high dissolution and dispersion speed and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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