CN107510665A - Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof - Google Patents
Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof Download PDFInfo
- Publication number
- CN107510665A CN107510665A CN201610427591.XA CN201610427591A CN107510665A CN 107510665 A CN107510665 A CN 107510665A CN 201610427591 A CN201610427591 A CN 201610427591A CN 107510665 A CN107510665 A CN 107510665A
- Authority
- CN
- China
- Prior art keywords
- parts
- oxiracetam
- levo
- ethanol
- recipe quantity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- 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
-
- 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
-
- 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
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Botany (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
A kind of good levo-oxiracetam particle of content uniformity, it is made by following supplementary material：1 part of levo-oxiracetam, 1.2 ~ 1.8 parts of mannitol, 0.8 ~ 1.3 part of microcrystalline cellulose, 0.7 ~ 1.3 part of sodium carboxymethylcellulose, 0.9 ~ 1.5 part of lactose, 0.8 ~ 1.4 part of sorbierite, 0.13 ~ 0.18 part of talcum powder, 1.1 ~ 1.8 parts of Macrogol 4000,0.9 ~ 1.7 part of hydroxypropyl methylcellulose, 2 ~ 7 parts of the ethanol that volume fraction is 30% ~ 50%, 1.2 ~ 1.8 parts of honey, 8 ~ 13 parts of the ethanol that volume fraction is 70% ~ 90%；According to levo-oxiracetam particle pelletization produced by the present invention will not adhesion screen cloth, be easy to pelletize, product bisque amount is few, and grain diameter is homogeneous, good fluidity, not sub- angle is less than 36 °, and content uniformity is less than ± 5%, and granule content uniformity is good, the content RSD of multiple points is less than 2%, it is good to store process stability, product is not easy moisture absorption caking, and shelf life is up to 24 months, preparation technology simple possible, it is worth marketing.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of good levo-oxiracetam particle of content uniformity
And preparation method thereof.
Background technology
Oxiracetam (S-oxiracetam) is a kind of hydroxy-amino-butyric acid of synthesis (BABOB) cyclic derivatives, is only used
In central nervous system, cerebral cortex, hippocampus are mainly distributed on, has activation, protection or the functional rehabilitation for promoting nerve cell, changes
The mnemonic learning function of kind disturbance of intelligence patient, and medicine also acts in itself without direct vasoactive without central excitation,
Influence to ability of learning and memory is a kind of lasting facilitation.
The medicine listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Parenteral solution, 5ml
∶1g.It is domestic at present there was only oxiracetam capsule and parenteral solution listing, and main active used is racemic modification.Ye Lei
Deng mentioning levo-oxiracetam in the A patents of Publication No. CN 103735545 to the promoting wakening gone into a coma caused by alcoholism
Substantially, and dextrorotation Oxiracetam does not act on substantially, the above-mentioned rush of levo-oxiracetam wake up that effect is racemization Oxiracetam 2
Times；Levo-oxiracetam is notable to the promoting wakening of stupor caused by wound, anesthesia.Peak etc. is opened in Publication No. CN
Levo-oxiracetam is disclosed in 103599101 A patent to the study note of traumatic brain injury rat caused by hydraulic pressure and freely falling body
Recall cognition dysfunction to improve significantly, its drug effect is far above dextrorotation Oxiracetam.And the left-handed Auras of 200mg/kg
It is western smooth suitable with the effect of 400mg/kg Oxiracetams.Pharmacokinetic study results are shown：Levo-oxiracetam and dextrorotation are difficult to understand
La Xitan is in beasle dog body without obvious chiral inversion.It is difficult to understand that beasle dog single intravenous injection gives left-handed and 2 multiple doses racemizations
The equal no significant difference of the main pharmacokinetic parameters of levo-oxiracetam in blood plasma after La Xitan.The examinations such as safe pharmacology, anxious malicious, long poison
Test result to show, under isodose level, levo-oxiracetam is with Oxiracetam to the toxicity of animal subject or cell without bright
Significant difference is different.Above-mentioned preclinical result of study shows that levo-oxiracetam is the chief active that drug effect is played in Oxiracetam body
Composition, this product, which is used alone, can reduce Clinical practice dosage, reduce potential toxicity.
Existing levo-oxiracetam particle is primarily present the easy adhesion screen cloth of pelletization, granulation difficulty, mixed process main ingredient
Be not easy to be well mixed, content lack of homogeneity, preparation process particle bisque is more, and particle diameter is difficult to control, storage process stability compared with
Difference, 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 levo-oxiracetam particle that a kind of content uniformity is good, stability is good.
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 content uniformity, it is characterised in that it is using levo-oxiracetam as original
Material, adds a certain amount of filler, flavouring, adhesive, lubricant, coating material and is made；Wherein described filler is shallow lake
Powder, lactose, dextrin, Icing Sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose, glucose, sodium carboxymethylcellulose, sorbierite
In one or more；The flavouring is sweet sucrose, maltose, ethylmaltol, Sucralose, stevia rebaudianum, sorbierite, sweet dew
One or more in alcohol, glucose, aspartame；Described adhesive is water, ethanol, sucrose, starch slurry, dextrin, carboxymethyl
One or more in cellulose, polyvinylpyrrolidone, honey；The lubricant is talcum powder, magnesium stearate, poly- second two
One or more in alcohol, stearic acid, calcium stearate, lauryl sodium sulfate, superfine silica gel powder, magnesia, paraffin；The coating
Material is Macrogol 4000, Macrogol 6000, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene acetaldehyde diethylamine second
One or more in ester, hydroxypropyl methyl cellulose phthalate.
Inventor has found that rational prescription proportion relation coordinates specific supplementary material processing mode again in research process, can
So that above-mentioned levo-oxiracetam particle pelletization is easy to pelletize, will not adhesion screen cloth, product is not easy moisture absorption, will not adhesion knot
Block, grain diameter are uniform, and content uniformity is small, and product stability is good, and shelf life length, main ingredient is easier to mix, and content uniformity is good；On
State the good levo-oxiracetam particle of content uniformity, it is characterised in that it is made by the supplementary material of following weight proportion：It is left
Revolve 1 part of Oxiracetam, 1.2~1.8 parts of mannitol, 0.8~1.3 part of microcrystalline cellulose, 0.7~1.3 part of sodium carboxymethylcellulose,
0.9~1.5 part of lactose, 0.8~1.4 part of sorbierite, 0.13~0.18 part of talcum powder, 1.1~1.8 parts of Macrogol 4000, hydroxyl
2~7 parts of the ethanol, 1.2~1.8 parts of honey, volume fraction that third 0.9~1.7 part of methylcellulose, volume fraction are 30%~50%
For 70%~90% 8~13 parts of ethanol；The honey of recipe quantity is taken, is placed in iron pan, adds the purifying of 2 times of parts by weight of honey
Water, stir, be heated to 100~105 DEG C, be incubated 20~25 minutes, take out, with 80 mesh screens, take filtrate, add after letting cool
Enter the ethanol of volume fraction 70%~90% of recipe quantity, stirring and dissolving is standby；The levo-oxiracetam of recipe quantity is taken, at addition
The volume fraction just measured dissolves for 30%~50% ethanol solution, standby；Separately take mannitol, microcrystalline cellulose, carboxymethyl cellulose
Plain sodium, lactose, sorbierite are placed in Universalpulverizer, are placed in after crushed 100 mesh sieves in wet granulator, add above-mentioned processing
Good levo-oxiracetam ethanol solution and previous ready honey ethanol solution, start granulator (18 mesh nylon of installation
Sieve), 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 Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity, add water be made quality volume fraction for 8%~
10% coating solution, 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℃；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, sets 50~60rpm of spouting velocity, atomization pressure
Power 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, added
Enter in the particle after whole grain, produced with three-dimensional motion mixer mixing 10min~20min.
Further, in order that obtaining above-mentioned levo-oxiracetam granule content evenly, stability is more preferable, and shelf life is more
It is long, a kind of levo-oxiracetam particle, it is characterised in that it is made by the supplementary material of following weight proportion：Left-handed Aura west
Smooth 1 part, 1.5~1.7 parts of mannitol, 0.9~1.2 part of microcrystalline cellulose, 0.8~1.1 part of sodium carboxymethylcellulose, lactose 1.1
~1.3 parts, 0.9~1.2 part of sorbierite, 0.15~0.17 part of talcum powder, 1.3~1.5 parts of Macrogol 4000, hypromellose
3~6 parts of ethanol that 1.1~1.5 parts of element, volume fraction are 30%~50%, 1.5~1.7 parts of honey, volume fraction is 70%~
9~12 parts of 90% ethanol；The honey of recipe quantity is taken, is placed in iron pan, adds the purified water of 2 times of parts by weight of honey, stirring is equal
It is even, 100~105 DEG C are heated to, is incubated 20~25 minutes, is taken out, with 80 mesh screens, is taken filtrate, recipe quantity is added after letting cool
The ethanol of volume fraction 70%~90%, stirring and dissolving is standby；The levo-oxiracetam of recipe quantity is taken, adds the body of recipe quantity
Fraction dissolves for 30%~50% ethanol solution, standby；Separately take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, breast
Sugar, sorbierite are placed in Universalpulverizer, are placed in after crushed 100 mesh sieves in wet granulator, add the above-mentioned left side handled well
Oxiracetam ethanol solution and previous ready honey ethanol solution are revolved, starts granulator (18 mesh nylon mesh of installation), starts
Granulation；Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying, and drying time is 50~55 points
Clock；Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity are taken, adds water that the coating that quality volume fraction is 8%~10% is made
Liquid, 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；Will bag
Clothing liquid 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, continue air intake and dry, solution stops heating, cooling discharging after continuing heating after having sprayed 10~15 minutes；Will coating
Grain 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, after adding whole grain
Particle in, produced with three-dimensional motion mixer mixing 10min~20min.
The preparation method of the good levo-oxiracetam particle of a kind of content uniformity, it is characterised in that it is by following step
It is rapid obtained：
1. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs
Mix uniformly, be heated to 100~105 DEG C, be incubated 20~25 minutes, take out, with 80 mesh screens, take filtrate, body is added after letting cool
Fraction is 70%~90% ethanol, and stirring and dissolving is standby；
2. supplementary material pre-treatment：The volume fraction for taking the levo-oxiracetam addition recipe quantity of recipe quantity is 30%~50%
Ethanol dissolves, and obtains levo-oxiracetam ethanol solution, standby；The filler of recipe quantity, flavouring is taken to be placed in Universalpulverizer,
100 mesh sieves are crushed, it is standby；
3. granulation：Gained mixed accessories powder and levo-oxiracetam ethanol solution after pre-treatment are taken, is placed in wet granulation
In machine, adhesive is added, starts granulator (18 mesh nylon mesh of installation), starts to pelletize；
4. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Observe at any time
Particle boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause particle coking or gelatinization, and drying time is 50~55 points
Clock, ensure pellet moisture≤3%；
5. coating：
(1) configuration of coating solution：The coating material of recipe quantity is taken, it is 8%~10% to add water that quality volume fraction is made
Solution, it is standby；
(2) coating process：Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature 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, atomization
Pressure is 0.8~1.0bar, continues air intake and dries, and solution stops heating after continuing heating after having sprayed 10~15 minutes, cools down out
Material, produces coated granule；
6. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, controls environment temperature
Less than 25 DEG C, relative humidity is below 50%；
It is 7. 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 8.：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature,
Below relative humidity 50%, produce.
The present invention has following beneficial effect：
Levo-oxiracetam particle pelletization of the present invention will not adhesion screen cloth, be easy to pelletize, product bisque amount is few, particle
Uniform particle diameter, good fluidity, not sub- angle are less than 36 °, and content uniformity is less than ± 5%, and granule content uniformity is good, and multiple points contain
Measure RSD and be less than 2%, storage process stability is good, and product is not easy moisture absorption caking, and shelf life is up to 24 months, preparation technology
Simple possible, it is worth marketing.
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 only used
It is further described in the present invention, it is impossible to limiting the scope of the invention is interpreted as, without departing substantially from spirit of the invention
In the case of essence, 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 good levo-oxiracetam particle of content uniformity, is made according to the following steps：
Preparation process：
1. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs
Mix uniformly, be heated to 100~105 DEG C, be incubated 20~25 minutes, take out, with 80 mesh screens, take filtrate, body is added after letting cool
Fraction is 70%~90% ethanol, and stirring and dissolving is standby；
2. supplementary material pre-treatment：The volume fraction for taking the levo-oxiracetam addition recipe quantity of recipe quantity is 30%~50%
Ethanol dissolves, and obtains levo-oxiracetam ethanol solution, standby；Take the mannitol, microcrystalline cellulose, carboxymethyl cellulose of recipe quantity
Sodium, lactose, sorbierite are placed in Universalpulverizer, crushed 100 mesh sieves, standby；
3. granulation：Gained mixed accessories powder and levo-oxiracetam ethanol solution after pre-treatment are taken, is placed in wet granulation
In machine, previously ready honey ethanol solution is added, starts granulator (18 mesh nylon mesh of installation), starts to pelletize；
4. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Observe at any time
Particle boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause particle coking or gelatinization, and drying time is 50~55 points
Clock, ensure pellet moisture≤3%；
5. coating：
(1) configuration of coating solution：Macrogol 4000, the hydroxypropyl methylcellulose of recipe quantity are taken, adds water that quality volume is made
Fraction is 8%~10% solution, standby；
(2) coating process：Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature 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, atomization
Pressure is 0.8~1.0bar, continues air intake and dries, and solution stops heating after continuing heating after having sprayed 10~15 minutes, cools down out
Material, produces coated granule；
6. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, controls environment temperature
Less than 25 DEG C, relative humidity is below 50%；
It is 7. total mixed：The talcum powder of recipe quantity be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion
Conjunction machine mixing 10min~20min；
Wrapped in 8.：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature,
Below relative humidity 50%, produce.
In pelletization, observation understands that the pelletization of embodiment 1 does not find the situation of adhesion screen cloth, and product is easy to make
Grain.
In order to be better understood from the present invention, having for invention medicine is expanded on further below by way of stability test of the present invention
Beneficial effect, rather than limitation of the present invention.
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 particle flow
Property is good.
Experiment two：Content uniformity
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 5g, content detection is carried out according to content assaying method, the content RSD of each sample point is calculated, evaluates whether to be well mixed；
3. result of the test：
4. conclusion (of pressure testing)：It can be seen that by upper table result of the test, this product content uniformity is good, and RSD is less than 2%
Experiment three：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 with indicating loading amount phase
Compare.
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 loading amount is poor
Different stabilization, content uniformity are small.
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, puts Acceleration study case
In, certain 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
Record：
Acceleration study result shows：Acceleration sample in June is suitable with 0 month sample items Testing index quality, shows that this product adds
Speed is tested June, and quality keeps stable, and this product stability is preferable.
Long-term experiment method：Levo-oxiracetam particle made from embodiment 1 is packed by listing, puts the long-term case that keeps sample
In, certain 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
Month 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 good levo-oxiracetam particle of content uniformity, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Observation product pelletization does not find showing for adhesion screen cloth
As product is easy to pelletize.Tested by the test method of embodiment 1, not sub- angle experiment measurement result shows this product particle stream
Dynamic property is good, and not sub- angle is less than 35 °, and content uniformity test result shows that this product content uniformity is good, its total mixed rear each point particle
Content RSD be less than 1%, content uniformity experiment shows that this product content uniformity is less than ± 5%, and this product loading amount is stable, controllable, stable
Property result of the test show to accelerate June sample quality stable, long-term 24 months steady qualities, therefore this product term of validity at least 24 months.
Embodiment 3
A kind of good levo-oxiracetam particle of content uniformity, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Observation product pelletization does not find showing for adhesion screen cloth
As product is easy to pelletize.Tested by the test method of embodiment 1, not sub- angle experiment measurement result shows this product particle stream
Dynamic property is good, and not sub- angle is less than 35 °, and content uniformity test result shows that this product content uniformity is good, its total mixed rear each point particle
Content RSD be less than 2%, content uniformity experiment shows that this product content uniformity is less than ± 4%, and this product loading amount is stable, controllable, stable
Property result of the test show to accelerate June sample quality stable, long-term 24 months steady qualities, therefore this product term of validity at least 24 months.
Embodiment 4-6：The good levo-oxiracetam particle of a kind of content uniformity, by the supplementary material preparation of following weight
, preparation method is the same as embodiment 1：
| Embodiment | 4 | 5 | 6 |
| Levo-oxiracetam | 1 part | 1 part | 1 part |
| Mannitol | 1.7 part | 1.6 part | 1.5 part |
| Microcrystalline cellulose | 1.0 part | 1.1 part | 1.0 part |
| Sodium carboxymethylcellulose | 1.0 part | 0.9 part | 1.0 part |
| Lactose | 1.2 part | 1.3 part | 1.1 part |
| Sorbierite | 1.1 part | 1.0 part | 1.1 part |
| Talcum powder | 0.17 part | 0.16 part | 0.15 part |
| Macrogol 4000 | 1.3 part | 1.4 part | 1.5 part |
| Hydroxypropyl methylcellulose | 1.2 part | 1.3 part | 1.4 part |
| Volume fraction is 40% ethanol | 5 parts | 4 parts | 5 parts |
| Honey | 1.5 part | 1.6 part | 1.7 part |
| Volume fraction is 80% ethanol | 10 parts | 10 parts | 10 parts |
Preparation process：It is made according to the preparation technology of embodiment 1.The observation product pelletization of embodiment 4,5,6 does not find to glue
The even phenomenon of screen cloth, therefore product is easy to pelletize.Tested by the test method of embodiment 1, the sample of embodiment 4,5,6 stops sub- angle
Experiment measurement result shows that this product mobility of particle is good, and not sub- angle is respectively lower than 35 °, 34 °, 35 °, and the sample of embodiment 4,5,6 contains
Amount uniformity test result shows that this product content uniformity is good, after it is total mixed content RSD of each point particle be respectively smaller than 2%,
1%th, 2%, the experiment of the sample content uniformity of embodiment 4,5,6 shows that this product content uniformity is respectively less than ± 4%, and this product loading amount is stable,
Controllable, the stability test result of embodiment 4,5,6 shows that acceleration sample quality in June is stable, long-term 24 months steady qualities, therefore this
The product term of validity at least 24 months.
Claims (3)
1. the good levo-oxiracetam particle of a kind of content uniformity, it is characterised in that it is by the former auxiliary of following weight proportion
Material is made according to the following steps：1 part of levo-oxiracetam, 1.2 ~ 1.8 parts of mannitol, 0.8 ~ 1.3 part of microcrystalline cellulose, carboxymethyl are fine
Tie up plain 0.7 ~ 1.3 part of sodium, 0.9 ~ 1.5 part of lactose, 0.8 ~ 1.4 part of sorbierite, 0.13 ~ 0.18 part of talcum powder, Macrogol 4000
1.1 ~ 1.8 parts, 0.9 ~ 1.7 part of hydroxypropyl methylcellulose, volume fraction be 30% ~ 50% 2 ~ 7 parts of ethanol, 1.2 ~ 1.8 parts of honey, body
Fraction is 70% ~ 90% 8 ~ 13 parts of ethanol；The honey of recipe quantity is taken, is placed in iron pan, adds the purifying of 2 times of parts by weight of honey
Water, stir, be heated to 100 ~ 105 DEG C, be incubated 20 ~ 25 minutes, take out, with 80 mesh screens, take filtrate, added after letting cool
The ethanol of volume fraction 70% ~ 90% of recipe quantity, stirring and dissolving are standby；The levo-oxiracetam of recipe quantity is taken, adds recipe quantity
Volume fraction dissolves for 30% ~ 50% ethanol solution, standby；It is another take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose,
Sorbierite is placed in Universalpulverizer, is placed in after crushed 100 mesh sieves in wet granulator, adds above-mentioned left-handed Austria handled well
La Xitan ethanol solutions and previous ready honey ethanol solution, 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；Take place
Macrogol 4000, the hydroxypropyl methylcellulose just measured, add water that the coating solution that quality volume fraction is 8% ~ 10% is made, it is standby；Will
In above-mentioned dry particl input fluid bed, hot-air is passed through, is 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 maintenance and operations
Dynamic mixer mixing 10min ~ 20min is produced.
2. levo-oxiracetam particle as claimed in claim 1, it is characterised in that it is by the supplementary material of following weight proportion
It is made according to the following steps：1 part of levo-oxiracetam, 1.5 ~ 1.7 parts of mannitol, 0.9 ~ 1.2 part of microcrystalline cellulose, carboxymethyl cellulose
Plain 0.8 ~ 1.1 part of sodium, 1.1 ~ 1.3 parts of lactose, 0.9 ~ 1.2 part of sorbierite, 0.15 ~ 0.17 part of talcum powder, Macrogol 4000
1.3 ~ 1.5 parts, 1.1 ~ 1.5 parts of hydroxypropyl methylcellulose, volume fraction be 30% ~ 50% 3 ~ 6 parts of ethanol, 1.5 ~ 1.7 parts of honey, body
Fraction is 70% ~ 90% 9 ~ 12 parts of ethanol；The honey of recipe quantity is taken, is placed in iron pan, adds the purifying of 2 times of parts by weight of honey
Water, stir, be heated to 100 ~ 105 DEG C, be incubated 20 ~ 25 minutes, take out, with 80 mesh screens, take filtrate, added after letting cool
The ethanol of volume fraction 70% ~ 90% of recipe quantity, stirring and dissolving are standby；The levo-oxiracetam of recipe quantity is taken, adds recipe quantity
Volume fraction dissolves for 30% ~ 50% ethanol solution, standby；It is another take mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose,
Sorbierite is placed in Universalpulverizer, is placed in after crushed 100 mesh sieves in wet granulator, adds above-mentioned left-handed Austria handled well
La Xitan ethanol solutions and previous ready honey ethanol solution, 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；Take place
Macrogol 4000, the hydroxypropyl methylcellulose just measured, add water that the coating solution that quality volume fraction is 8% ~ 10% is made, it is standby；Will
In above-mentioned dry particl input fluid bed, hot-air is passed through, is 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 maintenance and operations
Dynamic mixer mixing 10min ~ 20min is produced.
3. the preparation method of levo-oxiracetam particle as claimed in claim 1 or 2, it is characterised in that it is by following step
It is rapid obtained：
A. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, adds the purified water of 2 times of parts by weight of honey, stirring
Uniformly, 100 ~ 105 DEG C are heated to, is incubated 20 ~ 25 minutes, is taken out, with 80 mesh screens, is taken filtrate, volume integral is added after letting cool
Number is 70% ~ 90% ethanol, and stirring and dissolving is standby；
B. supplementary material pre-treatment：Take the volume fraction of the levo-oxiracetam addition recipe quantity of recipe quantity molten for 30% ~ 50% ethanol
Solution, obtains levo-oxiracetam ethanol solution, standby；Take the filler of recipe quantity, flavouring to be placed in Universalpulverizer, crushed
100 mesh sieves, it is standby；
C. pelletize：Gained mixed accessories powder and levo-oxiracetam ethanol solution after pre-treatment are taken, is placed in wet granulator,
Adhesive is added, starts granulator（18 mesh nylon mesh are installed）, start to pelletize；
D. 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 ensured
Pellet moisture≤3%；
E. it is coated：
The configuration of E (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
With；
E (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；
F. whole grain, sub-sieve:Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, controls 25 DEG C of environment temperature
Hereinafter, relative humidity is below 50%；
G. 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；
H. interior bag：Packed with particles packing machine, set packing specification as 1g/ bags, controlled below 25 DEG C of environment temperature, relatively
Below humidity 50%, produce.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610427591.XA CN107510665A (en) | 2016-06-15 | 2016-06-15 | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610427591.XA CN107510665A (en) | 2016-06-15 | 2016-06-15 | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107510665A true CN107510665A (en) | 2017-12-26 |
Family
ID=60720064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610427591.XA Withdrawn CN107510665A (en) | 2016-06-15 | 2016-06-15 | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107510665A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993006826A1 (en) * | 1991-10-08 | 1993-04-15 | Smithkline Beecham Farmaceutici S.P.A. | Composition comprising s-oxiracetame for use as nootropic |
| 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 |
| CN103599101A (en) * | 2013-11-08 | 2014-02-26 | 南京优科生物医药研究有限公司 | Application of levo-oxiracetam in preparation of medicine for treating memory and intelligence disturbance |
-
2016
- 2016-06-15 CN CN201610427591.XA patent/CN107510665A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993006826A1 (en) * | 1991-10-08 | 1993-04-15 | Smithkline Beecham Farmaceutici S.P.A. | Composition comprising s-oxiracetame for use as nootropic |
| 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 |
| CN103599101A (en) * | 2013-11-08 | 2014-02-26 | 南京优科生物医药研究有限公司 | Application of levo-oxiracetam in preparation of medicine for treating memory and intelligence disturbance |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107510657A (en) | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof | |
| CN107510665A (en) | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof | |
| CN106619526A (en) | Good-stability (S)-4-hydroxy-2 oxo-1-pyrrolidine acetamide granule and preparation method thereof | |
| CN107510684A (en) | Good levo-oxiracetam particle of a kind of content uniformity and preparation method thereof | |
| CN107510664A (en) | A kind of levo-oxiracetam particle and preparation method thereof | |
| CN107510679A (en) | A kind of content is uniform（S）Pyrrolidine acetamide particle of 4 hydroxyl, 2 oxo 1 and preparation method thereof | |
| CN107510685A (en) | Uniform oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 of a kind of content and preparation method thereof | |
| CN106943376B (en) | A kind of levo-oxiracetam particle and preparation method thereof | |
| CN107510672A (en) | Good oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 of a kind of stability and preparation method thereof | |
| CN106606485A (en) | Good taste levo S-oxiracetam particle and preparation method thereof | |
| CN107510667A (en) | A kind of stability is good（S）Oxo-1-pyrrolidine ethanamide particle of -4- hydroxyls -2 and preparation method thereof | |
| CN107510656A (en) | Good oxo-1-pyrrolidine ethanamide particle of (S) -4- hydroxyls -2 of a kind of stability and preparation method thereof | |
| CN106619529A (en) | Levorotatory oxiracetam granule with good content uniformity and preparation method thereof | |
| CN107510663A (en) | A kind of levo-oxiracetam particle in good taste and preparation method thereof | |
| CN107510674A (en) | A kind of levo-oxiracetam particle in good taste and preparation method thereof | |
| CN107510676A (en) | A kind of content is uniform（S）Pyrrolidine acetamide particle of 4 hydroxyl, 2 oxo 1 and preparation method thereof | |
| CN106943377A (en) | A kind of levo-oxiracetam particle and preparation method thereof | |
| CN107510677A (en) | A kind of levo-oxiracetam particle in good taste and preparation method thereof | |
| CN107510673A (en) | One kind leaches fireballing levo-oxiracetam particle and preparation method thereof | |
| CN106619525A (en) | (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide particles having uniform content, and preparation method thereof | |
| CN107510678A (en) | One kind leaches fireballing levo-oxiracetam particle and preparation method thereof | |
| CN107510681A (en) | It is a kind of（S）Pyrrolidine acetamide particle of 4 hydroxyl, 2 oxo 1 and preparation method thereof | |
| CN107510658A (en) | Oxo-1-pyrrolidine ethanamide particle of one kind (S) -4- hydroxyls -2 and preparation method thereof | |
| CN107510683A (en) | One kind leaches fireballing levo-oxiracetam particle and preparation method thereof | |
| CN106619523A (en) | (S)-4-hydroxy-dioxo-1-pyrrolidine acetamide particles and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20171226 |