CN106619527A - (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide granules realizing rapid dissolution and preparation method thereof - Google Patents
(S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide granules realizing rapid dissolution and preparation method thereof Download PDFInfo
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- CN106619527A CN106619527A CN201510705313.1A CN201510705313A CN106619527A CN 106619527 A CN106619527 A CN 106619527A CN 201510705313 A CN201510705313 A CN 201510705313A CN 106619527 A CN106619527 A CN 106619527A
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Abstract
The invention provides (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide granules realizing rapid dissolution. The (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide granules are prepared from the following raw materials and auxiliary materials in parts by weight: about 1 part of (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide, about 1.5-1.9 parts of mannitol, about 0.8-1.2 parts of microcrystalline cellulose, about 0.6-1.0 part of sodium carboxymethylcellulose, about 0.6-1.3 parts of lactose, about 0.08-0.15 part of magnesium stearate, about 1.0-1.5 parts of polyethylene glycol 4000, about 0.5-0.9 part of hydroxypropyl methylcellulose, about 1.2-1.6 parts of low-substituted hydroxypropyl cellulose, about 0.12-0.18 part of polysorbate 80, about 0.8-1.3 parts of sorbitol, and about 5-12 parts of ethanol solution with the volume fraction being 50%-70%. The (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide granules prepared by adopting the method provided by the invention have good granule content uniformity, the RSD of contents of a plurality of points is smaller than 1%, the dissolution speed is high, the time consumed for completely dissolving the granules is shorter than 30 seconds, during the storage process, the stability is good, the product has small possibility of moisture absorption and caking, the shelf life of the product is as long as 36 months, and in addition, the preparation process is simple and feasible, and suitable for market promotion.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of to leach the fast oxo -1- pyrroles of (S) -4- hydroxyls -2
Alkyl acetamide particle and preparation method thereof.
Background technology
Cereboactive drug is a kind of new medicine for central nervous system for promoting study, strengthening memory also known as cereboactive drug.Promote
Intelligence medicine requires selection index system 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 network or olfactory bulb, but directly
Connect and act on cortex.Behavior is neither affected, 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-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.
The existing oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 is primarily present main ingredient and is difficult to be well mixed, and content is equal
Even property is poor, and preparation process particle bisque is more, and particle diameter is wayward, and storage process stability is poor, and particle hygroscopicity is strong,
Connecting block easy to stick, shelf life is short, and particle leaches speed slowly, etc. technical problem.
The content of the invention
It is an object of the invention to provide one kind is leached soon, the OXo-1-pyrrolidine acetyl of (S) -4- hydroxyls -2 of good stability
Amine particle.
Another object of the present invention is to provide the preparation side of the above-mentioned oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2
Method.
The purpose of the present invention is realized by following technical measures：
A kind of oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 in good taste, it is with the oxygen of (S) -4- hydroxyls -2
Generation -1- pyrrolidine acetamides are raw material, add a certain amount of filler, flavouring, adhesive, lubricant, disintegrant,
Coating material is obtained；Wherein described filler is starch, lactose, dextrin, Icing Sugar, calcium sulfate, sucrose, mannitol, crystallite
One or more in cellulose, glucose, sodium carboxymethylcellulose, sorbierite；The flavouring be sucrose, maltose,
Ethylmaltol, Sucralose, stevia rebaudianum are sweet, one or more in sorbierite, mannitol, glucose, aspartame；Institute
Adhesive is stated for the one kind or many in water, ethanol, sucrose, starch slurry, dextrin, carboxymethylcellulose calcium, polyvinylpyrrolidone
Kind；The lubricant is talcum powder, magnesium stearate, polyethylene glycol, stearic acid, calcium stearate, lauryl sodium sulfate, micro-
One or more in powder silica gel, magnesia, paraffin；The disintegrant be low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate,
One or more in sodium carboxymethyl starch, dried starch；The coating material be Macrogol 4000, Macrogol 6000,
One kind in hydroxypropyl cellulose, Hydroxypropyl methylcellulose, AEA, hydroxypropyl methyl cellulose phthalate
Or it is various.
The rational prescription proportioning of inventor, coordinates specific preparation method, can cause the above-mentioned OXo-1-pyrrolidine of (S) -4- hydroxyls -2
Acetamide particle main ingredient in preparation process is well mixed, and content uniformity is good, and product storage process is difficult moisture absorption, is difficult
Adhesion caking, good stability, shelf life is long, and it is fast that particle leaches speed；It is above-mentioned to leach the fast oxo of (S) -4- hydroxyls -2
- 1- pyrrolidine acetamide particles, it is characterised in that it is obtained by the supplementary material of following weight proportion：(S) -4- hydroxyls -2
1 part of oxo-1-pyrrolidine ethanamide, 1.5～1.9 parts of mannitol, 0.8～1.2 part of microcrystalline cellulose, carboxymethylcellulose calcium
0.6～1.0 part of sodium, 0.6～1.3 part of lactose, 0.08～0.15 part of magnesium stearate, 1.0～1.5 parts of Macrogol 4000, hydroxyl
Third 0.5～0.9 part of methylcellulose, 1.2～1.6 parts of low-substituted hydroxypropyl cellulose, 0.12～0.18 part of polyoxyethylene sorbitan monoleate, mountain
0.8～1.3 part of pears alcohol, 5～12 parts of the ethanol solution that volume fraction is 50%～70%；Take the oxo -1- of (S) -4- hydroxyls -2
Pyrrolidine acetamide is dissolved in ethanol solution, standby；Separately take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose,
Lactose, low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate, sorbierite are placed in Universalpulverizer, crush 100 mesh
It is placed in after sieve in wet granulator, adds the previously processed good oxo-1-pyrrolidine ethanamide ethanol of (S) -4- hydroxyls -2 molten
Liquid, starts granulator (installing 24 mesh nylon mesh), starts granulation；Wet granular is put in air dry oven, temperature is set
50 DEG C～60 DEG C drying times of degree are 120min～150min so that particle water content≤3% (weight/mass percentage composition)；Take
The Macrogol 4000 and Hydroxypropyl methylcellulose of recipe quantity, add water the coating solution for making that mass fraction is 6%～9%, 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；By coating solution
Fluid bed is continuously added to 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 has sprayed and stopped heating after rear continuation is heated 10～15 minutes, cooling discharging,
Obtain final product coated granule.
Further, in order that the drug content of the oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 evenly,
Leach speed faster；The above-mentioned oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2, it is characterised in that it is by under
The supplementary material of row weight proportion is obtained：(S) 1 part of -2 oxo-1-pyrrolidine ethanamide of -4- hydroxyls, 1.6～1.8 parts of mannitol,
0.9～1.2 part of microcrystalline cellulose, 0.8～1.0 part of sodium carboxymethylcellulose, 0.8～1.2 part of lactose, magnesium stearate 0.10～0.13
Part, 1.1～1.3 parts of Macrogol 4000,0.5～0.7 part of Hydroxypropyl methylcellulose, low-substituted hydroxypropyl cellulose 1.3～1.5
Part, 0.15～0.17 part of polyoxyethylene sorbitan monoleate, 0.9～1.2 part of sorbierite, the ethanol solution 6～9 that volume fraction is 50%～70%
Part；Take the oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 to be dissolved in ethanol solution, it is standby；Separately take mannitol, micro-
Crystalline cellulose, sodium carboxymethylcellulose, lactose, low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate, sorbierite are placed in
In Universalpulverizer, crushed and be placed in after 100 mesh sieves in wet granulator, added previously processed good (S) -4- hydroxyls
- 2 oxo-1-pyrrolidine ethanamide ethanol solutions, start granulator (installing 24 mesh nylon mesh), start granulation；By wet
In grain input air dry oven, setting temperature 50 C～60 DEG C drying time is 120min～150min so that particle is aqueous
≤ 3% (weight/mass percentage composition) of amount；The Macrogol 4000 and Hydroxypropyl methylcellulose of recipe quantity are taken, is added water and is made quality
Fraction is 6%～9% coating solution, standby；Above-mentioned dry particl is put in fluid bed, hot-air is passed through, is allowed to suspend
Fluidisation, bed temperature is 40～50 DEG C；Coating solution is continuously added to into fluid bed, setting whitewashing speed by the nozzle atomization of fluid bed
50～60rpm of degree, atomizing pressure is 0.8～1.0bar, continues air intake and is dried, and solution continues to heat 10～15 minutes after having sprayed
Stop heating afterwards, cooling discharging obtains final product coated granule.
A kind of preparation method for leaching the fast oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2, it is characterised in that
It is obtained as follows：
1. supplementary material pre-treatment：The oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 for taking recipe quantity is dissolved in recipe quantity
It is standby in adhesive；Separately take filler, flavouring, disintegrant to be placed in Universalpulverizer, crush 100 mesh sieves,
It is standby；
2. pelletize：Gained auxiliary material mixed-powder after pre-treatment is taken, in being placed in wet granulator, is added processed good (S)
The oxo-1-pyrrolidine ethanamide solution of -4- hydroxyls -2, 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：
The oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 has granule content uniformity good obtained in the present invention, many
Content RSD of individual point is less than 1%, leaches speed soon, and particle all leached the time less than 30 seconds, stored process stability
Good, product is difficult moisture absorption caking, and shelf life is up to 36 months, and preparation process is simple is feasible, is worth marketing.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be that following examples are served only for
The present invention is further described, it is impossible to be interpreted as limiting the scope of the invention, without departing substantially from spirit of the invention
In the case of essence, the modification made to the inventive method, step or condition or replacement belong to the scope of the present invention.
Embodiment 1
A kind of oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 for leaching, is obtained according to the following steps：
Preparation process：
1. supplementary material pre-treatment：The oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 for taking recipe quantity is dissolved in ethanol,
It is standby；Separately take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose, low substituted carboxymethyl cellulose, poly- mountain
Pear ester 80, sorbierite is placed in Universalpulverizer, crushes 100 mesh sieves, standby；
2. pelletize：Gained mixed accessories powder after pre-treatment is taken, in being placed in wet granulator, is added previously processed good (S)
The oxo-1-pyrrolidine ethanamide ethanol solution of -4- hydroxyls -2, 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：Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, is added water and is made mass fraction and be
6%～9% 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 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：Content uniformity
1. test material：Sample after the completion of always mixing in the preparation process of embodiment 1
2. test method：After the completion of embodiment 1 is always mixed, respectively in upper, middle and lower of three-dimensional motion mixer, left and right
The separately sampled 5g of each point, according to content assaying method content detection is carried out, and calculates content RSD of each sample point,
Evaluate whether to be well mixed；
3. result of the test：
4. conclusion (of pressure testing)：Can be seen that by upper table result of the test, this product content uniformity is good, RSD is less than 1%
Test two：Leach timing
1. test material：The oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 obtained in embodiment 1；
2. test method：10 bags of -2 oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls obtained in Example 1,
In being placed in 100ml beakers, the purified water that 50ml temperature is 25 DEG C is added, it is static, needed for observation is all leached
The time wanted；
3. result of the test see the table below：
| Test number | 1# | 2# | 3# | 4# | 5# |
| Leach the time (min) | 22 seconds | 26 seconds | 23 seconds | 18 seconds | 21 seconds |
| Test number | 6# | 7# | 8# | 9# | 10# |
| Leach the time (min) | 25 seconds | 27 seconds | 22 seconds | 21 seconds | 27 seconds |
4. conclusion (of pressure testing)：Can be seen that by upper table result of the test, repeatedly measurement particle leaches the time less than 30 seconds, it was demonstrated that press
It is fast that obtained particle of the invention leaches speed.
Test three：The present invention is a kind of to leach the fast oxo-1-pyrrolidine ethanamide granule stability of (S) -4- hydroxyls -2 experiment
Experiment material：(S) the oxo-1-pyrrolidine ethanamide particle of -4- hydroxyls -2：It is obtained for embodiment 1.
Acceleration study method：By the oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 obtained in embodiment 1 by listing
Packaging, in putting Acceleration study case, 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, 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 the oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 obtained in embodiment 1 by listing
Packaging, puts and keep sample for a long time in case, certain hour sampling, 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
It is a kind of to leach the fast oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2, it 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, content is carried out respectively equal
Even property is determined, leaches timing and sample stability test, and content uniformity test result shows that this product content is uniform
Property it is good, content RSD of each point particle is less than 1% after it is total mixed, and leaching timing, to show that this product leaches speed fast, many
Individual sample leaches the time and is respectively less than 30 seconds, and stability test result shows to accelerate June sample quality to stablize, long-term 36
Month steady quality, therefore this product term of validity at least 36 months, taste investigation shows that this product is delicious, easily by most of patient
Received.
Embodiment 3
It is a kind of to leach the fast oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2, it 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, content is carried out respectively equal
Even property is determined, leaches timing and sample stability test, and content uniformity test result shows that this product content is uniform
Property it is good, content RSD of each point particle is less than 1% after it is total mixed, and leaching timing, to show that this product leaches speed fast, many
Individual sample leaches the time and is respectively less than 30 seconds, and stability test result shows to accelerate June sample quality to stablize, long-term 36
Month steady quality, therefore this product term of validity at least 36 months, taste investigation shows that this product is delicious, easily by most of patient
Received.
Embodiment 4-6：A kind of oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 in good taste, by following weight
Supplementary material be prepared, preparation method is with embodiment 1：
| Embodiment | 4 | 5 | 6 |
| (S) oxo -1- of -4- hydroxyls -2 | 1 part | 1 part | 1 part |
| Pyrrolidine acetamide | |||
| Mannitol | 1.8 part | 1.7 part | 1.6 part |
| Microcrystalline cellulose | 1.0 part | 1.1 part | 1.2 part |
| Sodium carboxymethylcellulose | 1.0 part | 0.9 part | 0.8 part |
| Lactose | 1.1 part | 1.2 part | 1.0 part |
| Magnesium stearate | 0.12 part | 0.11 part | 0.12 part |
| Macrogol 4000 | 1.1 part | 1.2 part | 1.3 part |
| Hydroxypropyl methylcellulose | 0.7 part | 0.6 part | 0.5 part |
| Low-substituted hydroxypropyl cellulose | 1.3 part | 1.4 part | 1.5 part |
| Polyoxyethylene sorbitan monoleate | 0.17 part | 0.16 part | 0.15 part |
| Sorbierite | 0.10 part | 0.11 part | 0.12 part |
| The ethanol of volume fraction 60% | 7 parts | 9 parts | 8 parts |
Preparation process：It is obtained according to the preparation technology of embodiment 1.By the test method of embodiment 1, content is carried out respectively equal
Even property is determined, leaches timing and sample stability test, the content uniformity test result table of embodiment 4,5,6
Bright this product content uniformity is good, and content RSD of its total mixed rear each point particle is respectively less than 1%, and embodiment 4,5,6 is leached
It is fast that timing shows that this product leaches speed, and multiple samples leach the time and are respectively less than 30 seconds, and embodiment 4,5,6 is stablized
Property result of the test show to accelerate June sample quality to stablize, long-term 36 months steady qualities, therefore this product term of validity at least 36
Individual month, taste investigation showed that this product is delicious, was easily received by most of patient.
Claims (3)
1. it is a kind of to leach the fast oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2, it is characterised in that it is by under
The supplementary material and following steps of row weight proportion is obtained：(S) about 1 part of the oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, sweet
About 1.5～1.9 parts of alcohol of dew, about 0.8～1.2 part of microcrystalline cellulose, about 0.6～1.0 part of sodium carboxymethylcellulose, lactose about 0.6～1.3
Part, about 0.08～0.15 part of magnesium stearate, about 1.0～1.5 parts of Macrogol 4000, Hydroxypropyl methylcellulose about 0.5～0.9
Part, about 1.2～1.6 parts of low-substituted hydroxypropyl cellulose, about 0.12～0.18 part of polyoxyethylene sorbitan monoleate, sorbierite about 0.8～1.3
Part, about 5～12 parts of the ethanol solution that volume fraction is 50%～70%；Take the OXo-1-pyrrolidine acetyl of (S) -4- hydroxyls -2
Amine solvent is standby in ethanol solution；Separately take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose, low take
Be placed in Universalpulverizer for hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate, sorbierite, crushed be placed in after 100 mesh sieves it is wet
In method granulator, the previously processed good oxo-1-pyrrolidine ethanamide ethanol solution of (S) -4- hydroxyls -2 is added, start system
Grain machine (installs 24 mesh nylon mesh), starts granulation；Wet granular is put in air dry oven, temperature 50 C～60 are set
DEG C drying time is 120min～150min so that particle water content≤3% (weight/mass percentage composition)；Take the poly- of recipe quantity
Ethylene glycol 4000 and Hydroxypropyl methylcellulose, add water the coating solution for making that mass fraction is 6%～9%, standby；Will be above-mentioned dry
In particle input fluid bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature is 40～50 DEG C；By coating solution by 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, is continued
Air intake is dried, and solution stops heating after continuing to heat 10～15 minutes after having sprayed, and cooling discharging obtains final product coated granule.
2. the oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 as claimed in claim 1, it is characterised in that it
It is to be obtained by the supplementary material and following steps of following weight proportion：(S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 about 1
Part, about 1.6～1.8 parts of mannitol, about 0.9～1.2 part of microcrystalline cellulose, about 0.8～1.0 part of sodium carboxymethylcellulose, breast
About 0.8～1.2 part of sugar, about 0.10～0.13 part of magnesium stearate, about 1.1～1.3 parts of Macrogol 4000, Hydroxypropyl methylcellulose
About 0.5～0.7 part, about 1.3～1.5 parts of low-substituted hydroxypropyl cellulose, about 0.15～0.17 part of polyoxyethylene sorbitan monoleate, sorb
About 0.9～1.2 part of alcohol, about 6～9 parts of the ethanol solution that volume fraction is 50%～70%；Take the oxo -1- of (S) -4- hydroxyls -2
Pyrrolidine acetamide is dissolved in ethanol solution, standby；Separately take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose,
Lactose, low-substituted hydroxypropyl cellulose, polyoxyethylene sorbitan monoleate, sorbierite are placed in Universalpulverizer, crush 100 mesh
It is placed in after sieve in wet granulator, adds the previously processed good oxo-1-pyrrolidine ethanamide ethanol of (S) -4- hydroxyls -2 molten
Liquid, starts granulator (installing 24 mesh nylon mesh), starts granulation；Wet granular is put in air dry oven, temperature is set
50 DEG C～60 DEG C drying times of degree are 120min～150min so that particle water content≤3% (weight/mass percentage composition)；Take
The Macrogol 4000 and Hydroxypropyl methylcellulose of recipe quantity, add water the coating solution for making that mass fraction is 6%～9%, 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；By coating solution
Fluid bed is continuously added to 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 has sprayed and stopped heating after rear continuation is heated 10～15 minutes, cooling discharging,
Obtain final product coated granule.
3. it is a kind of as claimed in claim 1 or 2 to leach the fast oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2
Preparation method, it is characterised in that it is obtained as follows：
A. supplementary material pre-treatment：The oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2 for taking recipe quantity is dissolved in recipe quantity
It is standby in adhesive；Separately take filler, flavouring, disintegrant to be placed in Universalpulverizer, crush 100 mesh sieves,
It is standby；
B. pelletize：Gained auxiliary material mixed-powder after pre-treatment is taken, in being placed in wet granulator, is added processed good (S)
The oxo-1-pyrrolidine ethanamide solution of -4- hydroxyls -2, 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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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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