CN108066292A - A kind of levo-oxiracetam oral disnitegration tablet and preparation method thereof - Google Patents
A kind of levo-oxiracetam oral disnitegration tablet and preparation method thereof Download PDFInfo
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- CN108066292A CN108066292A CN201610995917.9A CN201610995917A CN108066292A CN 108066292 A CN108066292 A CN 108066292A CN 201610995917 A CN201610995917 A CN 201610995917A CN 108066292 A CN108066292 A CN 108066292A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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Abstract
The present invention provides a kind of levo-oxiracetam oral disnitegration tablets, using levo-oxiracetam solid dispersions as active ingredient, levo-oxiracetam oral disnitegration tablet is prepared with pharmaceutically acceptable required excipient, can under the conditions of anhydrous (or the only a small amount of water presence) fater disintegration in oral cavity, enter alimentary canal with swallowing act, internal behavior is consistent with conventional tablet, is very suitable for the patient of dysphagia.Levo-oxiracetam disintegrated tablet prepared by the present invention basic disintegration of 35s disintegrations in oral cavity is complete, and stability is good and the hardness of the disintegrated tablet of preparation is in 30~40N, is very suitable for producing, transports, packs, storing；Preparation method is simple, with short production cycle without special installation, at low cost, is suitble to industrialized production.
Description
Technical field
The present invention relates to levo-oxiracetams, and in particular to a kind of levo-oxiracetam oral disnitegration tablet and its preparation side
Method.
Background technology
Levo-oxiracetam (S-Oxiracetam), chemical name are -2 oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls.
Research shows that it can promote the synthesis of Phosphorylcholine and phosphatidyl ethanolamine, promotes brain metabolism, through blood-brain barrier in specificity
Pivot nerve road spinosity swashs effect, the neurological functional recovery of patient is acted on it is apparent, to light moderate vascular dementia, senile silly
The curative effect of disease such as slow-witted and various cerebrovascular diseases, cerebral injury, intracranial infection are preferable.Its structure is as follows：
Levo-oxiracetam
Although levo-oxiracetam good effect, safe, its pharmaceutical preparation is still in development phase.On left-handed Austria
La Xitan preparation researches focus primarily upon oral formulations and two aspect of injection (comprising freeze drying powder injection).Injection, it is directly fast
Speed is into human body, the protection of no human body normal physiological barrier, if therefore dosage is improper or injection is too fast or drug quality presence is asked
Topic, it is possible that bringing harm to patient or even causing the consequence that can not be retrieved；In addition injection pain, cannot be by patient oneself
Administration, injection site, which lead to the problem of scleroma and be injected intravenously when vascular inflammation being caused all to be clinical practice, to be existed.Oral system
Agent (such as conventional tablet, capsule, sustained-release and controlled release piece, dispersible tablet), takes, carries, transports and stores and is all more convenient.However
Levo-oxiracetam is and in the majority with the elderly primarily directed to the more low patient of intelligence, and this kind of patient is usually for drug
Dysphagia takes oxiracetam capsule agent, conventional tablet is inconvenient.
Oral disnitegration tablet, can under the conditions of anhydrous in oral cavity fater disintegration, enter alimentary canal, internal row with swallowing act
To be consistent with conventional tablet.Compared with ordinary preparation, have it is convenient to take, absorb that fast, bioavilability is high, alimentary canal mucous membrane is pierced
Swash the advantages that property is small, receive significant attention.Chinese patent CN101766595A discloses a kind of levo-oxiracetam Orally disintegrating
Piece is made using auxiliary materials such as levo-oxiracetam raw material, sodium carboxymethyl starch, croscarmellose sodiums by adhesive of water.
It is found when repeating the patent, since levo-oxiracetam water solubility is fabulous, hygroscopicity is strong, and material holds in wet-granulation process
It is easily agglomerating, while most of material is sticked in granulation pot wall, is caused particle uneven, is increased the difficulty of granulation, it is difficult to obtain
Uniformly mixed and relatively narrow particle diameter distribution particle, and compressibility is poor, is unfavorable for preparation production.
The content of the invention
The defects of in order to overcome the prior art, according in a first aspect, it is an object of the invention to provide a kind of left-handed Auras
Western smooth oral disnitegration tablet.
Unless otherwise specified, number of the present invention is parts by weight, and the percentage is mass percent.
The object of the present invention is achieved like this：
A kind of levo-oxiracetam oral disnitegration tablet contains active ingredient and pharmaceutically acceptable required excipient；Institute
Active ingredient is stated as levo-oxiracetam solid dispersions, the excipient includes filler, disintegrant, lubricant or/and rectifys
Taste agent.
An embodiment according to the present invention, above-mentioned levo-oxiracetam oral disnitegration tablet, which contains levo-oxiracetam, to be consolidated
Body dispersion 0.8~14%, filler 55~70%, disintegrant 8~25%, lubricant 1~5%, corrigent 0.1~1%.
An embodiment according to the present invention, above-mentioned levo-oxiracetam solid dispersions are by levo-oxiracetam, load
Body and solvent are made；The carrier is succinic acid, beta-cyclodextrin, Macrogol 6000, polyvinylpyrrolidone, lactose, pool Lip river
The mixing of one or more of husky nurse 188, hydroxypropyl cellulose；The solvent is absolute ethyl alcohol, 95% ethyl alcohol, acetone, dichloro
The mixing of one or more of methane, ethyl acetate.
An embodiment according to the present invention, above-mentioned levo-oxiracetam solid dispersions are made by solvent method.
In order to improve the dissolution efficiency of levo-oxiracetam oral disnitegration tablet, an embodiment according to the present invention, on
Levo-oxiracetam solid dispersions are stated by 1 part of levo-oxiracetam, 1~12 part of carrier and 15~80 parts of solvents by solvent legal system
.
An embodiment according to the present invention, above-mentioned levo-oxiracetam solid dispersions by 1 part of levo-oxiracetam,
1~8 part of succinic acid and 15~50 parts of absolute ethyl alcohols are made by solvent method.
Or
An embodiment according to the present invention, above-mentioned levo-oxiracetam solid dispersions by 1 part of levo-oxiracetam,
3~12 parts of PLURONICS F87s and 30~80 parts of acetone are made by solvent method.
An embodiment according to the present invention, above-mentioned filler for cornstarch, amylum pregelatinisatum, microcrystalline cellulose,
The mixing of one or more of medicinal calcium carbonate, mannitol.
An embodiment according to the present invention, above-mentioned disintegrant is dried starch, sodium carboxymethyl starch, low substituted hydroxy-propyl
The mixing of one or more of cellulose, crosslinked polyvinylpyrrolidone, croscarmellose sodium.
An embodiment according to the present invention, above-mentioned lubricant are magnesium stearate, superfine silica gel powder, talcum powder, hydrogenation plant
The mixing of one or more of object oil.
An embodiment according to the present invention, above-mentioned corrigent for Sucralose, xylitol, acesulfame potassium, Aspartame,
The mixing of one or more of essence.
In order to control the disintegration time limited of levo-oxiracetam oral disnitegration tablet, an embodiment according to the present invention, on
Filler is stated as one or more compositions in amylum pregelatinisatum, microcrystalline cellulose, mannitol；Disintegrant low substituted hydroxy-propyl is fine
The mixture of plain, in crosslinked polyvinylpyrrolidone the one or both of dimension.
An embodiment according to the present invention, above-mentioned filler is amylum pregelatinisatum and mannitol mixture, wherein can
Pressure property starch：Weight ratio=1~3 of mannitol:1；Above-mentioned disintegrant is low-substituted hydroxypropyl cellulose and crosslinked polyethylene pyrrole
The mixture of pyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2~5:1.
Or
An embodiment according to the present invention, above-mentioned filler are amylum pregelatinisatum, microcrystalline cellulose and mannitol
Mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1~2 of mannitol:2~3：1；Above-mentioned disintegrant takes to be low
For hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinked polyethylene
The weight ratio of pyrrolidones is 1~3:1.
Or
An embodiment according to the present invention, above-mentioned filler is microcrystalline cellulose and mannitol mixture, wherein micro-
Crystalline cellulose：Weight ratio=2~5 of mannitol:1；Above-mentioned disintegrant is low-substituted hydroxypropyl cellulose and crosslinked polyethylene pyrrole
The mixture of pyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2~3:1.
To further enhance the production compliance of the present invention, an embodiment according to the present invention, above-mentioned left-handed Aura
Western smooth oral disnitegration tablet contains active ingredient and pharmaceutically acceptable required excipient；The active ingredient is left-handed Aura
Western smooth solid dispersions, the excipient include filler, disintegrant, lubricant or/and corrigent；The levo-oxiracetam
Solid dispersions are made by 1 part of levo-oxiracetam, 1~8 part of succinic acid and 20~50 parts of absolute ethyl alcohols by solvent method；It is described to fill out
Agent is filled for amylum pregelatinisatum and mannitol mixture, wherein amylum pregelatinisatum：Weight ratio=1~3 of mannitol:1；The disintegration
Agent is low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：It hands over
The weight ratio for joining polyvinylpyrrolidone is 2~5:1；The lubricant is superfine silica gel powder；The corrigent for Sucralose or
Aspartame.
To further enhance the production compliance of the present invention, an embodiment according to the present invention, above-mentioned left-handed Aura
Western smooth oral disnitegration tablet contains active ingredient and pharmaceutically acceptable required excipient；The active ingredient is left-handed Aura
Western smooth solid dispersions, the excipient include filler, disintegrant, lubricant or/and corrigent；The levo-oxiracetam
Solid dispersions are made by 1 part of levo-oxiracetam, 1~8 part of succinic acid and 20~40 parts of absolute ethyl alcohols by solvent method；It is described to fill out
Agent is filled for amylum pregelatinisatum, microcrystalline cellulose and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Mannitol
Weight ratio=1~2:2~3：1；The disintegrant is the mixing of low-substituted hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone
Object, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 1~3:1；The lubricant is micro mist
Silica gel；The corrigent is Aspartame.
For the production compliance of the enhancing present invention, an embodiment according to the present invention, above-mentioned levo-oxiracetam mouth
Cavity disintegrating tablet contains active ingredient and pharmaceutically acceptable required excipient；The active ingredient is consolidated for levo-oxiracetam
Body dispersion, the excipient include filler, disintegrant, lubricant or/and corrigent；The levo-oxiracetam solid point
Granular media is made by 1 part of levo-oxiracetam, 3~12 parts of PLURONICS F87s and 40~60 parts of acetone by solvent method；The filler
For microcrystalline cellulose and mannitol mixture, wherein microcrystalline cellulose：Weight ratio=2~5 of mannitol:1；The disintegrant is
The mixture of low-substituted hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinking is poly-
The weight ratio of vinylpyrrolidone is 2~3:1；The lubricant is superfine silica gel powder；The corrigent is Sucralose.
According to second aspect, it is an object of the invention to provide the preparation sides of above-mentioned levo-oxiracetam oral disnitegration tablet
Method.This method adds in filler, disintegrant, lubricant or/and corrigent tabletting system with levo-oxiracetam solid dispersions
.
An embodiment according to the present invention, the preparation method of levo-oxiracetam oral disnitegration tablet, using following step
Suddenly：
(1) solid dispersions are prepared
Levo-oxiracetam in solvent, stirs 5~25min with carrier uniform dissolution, and recycling design dry, pulverize, mistake
100 mesh sieves are to get solid dispersions.
(2) preparation of oral disnitegration tablet
By obtained levo-oxiracetam solid dispersions addition filler, 30~60% disintegrant (disintegrant that sieve
The 30~60% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
An embodiment according to the present invention, the preparation method of above-mentioned levo-oxiracetam oral disnitegration tablet, using such as
Lower step：
(1), solid dispersions are prepared
1 part of levo-oxiracetam and 1~8 part of succinic acid uniform dissolution in 20~50 parts of absolute ethyl alcohols, stirring 5~
25min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains levo-oxiracetam solid dispersions 0.8~14%, filler 55~70%, disintegrant 8
~25%, lubricant 1~5%, corrigent 0.1~1%；Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Advantageous effect：
The present invention provides a kind of levo-oxiracetam oral disnitegration tablet, can under the conditions of anhydrous (or only a small amount of water
In the presence of) fater disintegration in oral cavity, enter alimentary canal with swallowing act, internal behavior is consistent with conventional tablet, is very suitable for swallowing
Difficult patient.The present invention uses levo-oxiracetam solid dispersions as active ingredient and pharmaceutically acceptable required
Excipient prepares levo-oxiracetam oral disnitegration tablet, effectively solves levo-oxiracetam bulk pharmaceutical chemicals hygroscopicity and causes by force
Material is easily agglomerating in pelletization, and material is sticked in granulation pot wall, is caused the non-uniform technical problem of particle, is effectively ensured
Levo-oxiracetam oral disnitegration tablet produces compliance.The present invention by the further control of solid dispersions and excipient, from
And it is effectively guaranteed the disintegration time limited of Orally disintegrating so that the levo-oxiracetam disintegrated tablet of preparation 35s in oral cavity is disintegrated
Basic disintegration is complete, and stability is good and the hardness of the disintegrated tablet of preparation is in 30~40N, is very suitable for producing, transports, packs, storing up
It deposits.Oral disnitegration tablet prepared by the present invention, auxiliary material is cheap and easy to get, and preparation method is simple, with short production cycle without special installation,
It is at low cost, it is also very suitable for industrialized production；In short, the present invention has conspicuousness progress compared with the prior art.
Embodiment
The present invention is specifically described below by embodiment, it is necessary to which indicated herein is that following embodiment is only used
It is further described in the present invention, it is impossible to be interpreted as limiting the scope of the invention, person skilled in art can
Some nonessential modifications and adaptations are made to the present invention according to the invention described above content.The raw materials used in the present invention and reagent are equal
For commercial product.
First, oral disnitegration tablet prepares embodiment
Embodiment 1
(1), solid dispersions are prepared
1 part of levo-oxiracetam and 1~8 part of succinic acid uniform dissolution in 20~50 parts of absolute ethyl alcohols, stirring 5~
25min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 0.8~14% levo-oxiracetam solid dispersions, and 55~70% fillers (form sediment by compressibility
Powder and mannitol mixture, wherein amylum pregelatinisatum：Weight ratio=1~3 of mannitol:1), 8~25% disintegrants (low substitution
The mixture of hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinked polyethylene pyrrole
The weight ratio of pyrrolidone is 2~5:1), 1~5% lubricant (superfine silica gel powder), 0.1~1% corrigent (Sucralose or A Si
Ba Tian)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 2
(1) preparation of solid dispersions:
By 10g levo-oxiracetams and 50g succinic acids uniform dissolution in 350mL absolute ethyl alcohols, 20~22min is stirred,
With Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get left-handed Austria
La Xitan solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (8g) that step (1) sieving obtains are added in into filler (amylum pregelatinisatum 45g
With the mixture of mannitol 18g), 40~50% disintegrant (low-substituted hydroxypropyl cellulose 18g and crosslinked polyethylene pyrrolidines
The mixture of ketone 7g), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining
Disintegrant, corrigent (Aspartame 1g), lubricant (superfine silica gel powder 3g), it is tabletted.
Embodiment 3
(1) preparation of solid dispersions:
By 5g levo-oxiracetams and 40g succinic acids uniform dissolution in 250mL absolute ethyl alcohols, 20~22min is stirred, is used
Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get left-handed Aura
Western smooth solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (5g) that step (1) sieving obtains are added in into filler (amylum pregelatinisatum 35g
With the mixture of mannitol 30g), 40~50% disintegrant (low-substituted hydroxypropyl cellulose 22g and crosslinked polyethylene pyrrolidines
The mixture of ketone 5g), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining
Disintegrant, corrigent (Sucralose 0.5g), lubricant (superfine silica gel powder 2.5g), it is tabletted.
Embodiment 4
(1) preparation of solid dispersions:
By 3g levo-oxiracetams and 5g succinic acids uniform dissolution in 80mL absolute ethyl alcohols, 20~22min is stirred, with rotation
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get left-handed Aura west
Smooth solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (3g) that step (1) sieving obtains are added in into filler (amylum pregelatinisatum 50g
With the mixture of mannitol 20g), 40~50% disintegrant (low-substituted hydroxypropyl cellulose 20g and crosslinked polyethylene pyrrolidines
The mixture of ketone 5g), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining
Disintegrant, corrigent (Aspartame 0.5g), lubricant (superfine silica gel powder 1.5g), it is tabletted.
Embodiment 5
(1), solid dispersions are prepared
1 part of levo-oxiracetam and 1~8 part of succinic acid uniform dissolution in 20~40 parts of absolute ethyl alcohols, stirring 5~
25min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 0.8~14% levo-oxiracetam solid dispersions, and 55~70% fillers (form sediment by compressibility
Powder, microcrystalline cellulose and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1~2 of mannitol:2
~3：1), 8~25% disintegrants (low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low take
For hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 1~3:1), 1~5% lubricant (superfine silica gel powder), 0.1
~1% corrigent (Aspartame)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 6
(1), solid dispersions are prepared
4g levo-oxiracetams in 180mL absolute ethyl alcohols, stir 5~25min, with rotation with 6g succinic acids uniform dissolution
Evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 4g levo-oxiracetam solid dispersions, 65g fillers (amylum pregelatinisatum, microcrystalline cellulose
Element and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1 of mannitol:2：1), 25g disintegrants
(low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinking is poly-
The weight ratio of vinylpyrrolidone is 1:1), 5g lubricants (superfine silica gel powder), 1g corrigents (Aspartame)；
Specifically preparation process is：
The levo-oxiracetam solid dispersions that sieving is obtained add in filler, the 50% of disintegrant total amount, and use is anhydrous
Ethyl alcohol is wetting agent, and wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant and corrigent and profit
Lubrication prescription, it is tabletted.
Embodiment 7
(1), solid dispersions are prepared
6 parts of levo-oxiracetams and 7 parts of succinic acid uniform dissolutions stir 5~25min, with rotation in 35 parts of absolute ethyl alcohols
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 6g levo-oxiracetam solid dispersions, 68g fillers (amylum pregelatinisatum, microcrystalline cellulose
Element and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=2 of mannitol:3：1), 22g disintegrants
(low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinking is poly-
The weight ratio of vinylpyrrolidone is 3:1), 3g lubricants (superfine silica gel powder), 1g corrigents (Aspartame)；
Specifically preparation process is：
To sieve obtained levo-oxiracetam solid dispersions addition filler, the 40~50% of disintegrant total amount, use
Absolute ethyl alcohol is wetting agent, and wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant and corrigent
And lubricant, it is tabletted.
Embodiment 8
(1), solid dispersions are prepared
1 part of levo-oxiracetam and 8 parts of succinic acid uniform dissolutions stir 5~25min, with rotation in 40 parts of absolute ethyl alcohols
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 14g levo-oxiracetam solid dispersions, 56g fillers (amylum pregelatinisatum, microcrystalline cellulose
Element and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1 of mannitol:3：1), 25g disintegrants
(low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinking is poly-
The weight ratio of vinylpyrrolidone is 2:1), 4.5g lubricants (superfine silica gel powder), 0.5g corrigents (Aspartame)；
Specifically preparation process is：
The levo-oxiracetam solid dispersions that sieving is obtained add in filler, the 40% of disintegrant total amount), use is anhydrous
Ethyl alcohol is wetting agent, and wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant and corrigent and profit
Lubrication prescription, it is tabletted.
Embodiment 9
(1), solid dispersions are prepared
1 part of levo-oxiracetam and 3~12 parts of PLURONICS F87 uniform dissolutions in 40~60 parts of acetone, stirring 5~
25min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 0.8~14% levo-oxiracetam solid dispersions, 55~70% filler (microcrystalline celluloses
Element and mannitol mixture, wherein microcrystalline cellulose：Weight ratio=2~5 of mannitol:1), 8~25% disintegrants (low substitution
The mixture of hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinked polyethylene pyrrole
The weight ratio of pyrrolidone is 2~3:1), 1~5% lubricant (superfine silica gel powder), 0.1~1% corrigent (Sucralose)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 10
(2), solid dispersions are prepared
1 part of levo-oxiracetam and 8 parts of PLURONICS F87 uniform dissolutions stir 5~25min, with rotation in 50 parts of acetone
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 3g levo-oxiracetam solid dispersions, and (microcrystalline cellulose and mannitol mix 70g fillers
Close object, wherein microcrystalline cellulose：Weight ratio=5 of mannitol:1), (low-substituted hydroxypropyl cellulose and crosslinking are poly- for 23g disintegrants
The mixture of vinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 3:1),
3.2g lubricants (superfine silica gel powder), 0.8g corrigents (Sucralose)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 11
(3), solid dispersions are prepared
8g levo-oxiracetams in 350mL acetone, stir 5~25min, with rotation with 24g PLURONICS F87s uniform dissolution
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 8g levo-oxiracetam solid dispersions, and (microcrystalline cellulose and mannitol mix 68g fillers
Close object, wherein microcrystalline cellulose：Weight ratio=2 of mannitol:1), (low-substituted hydroxypropyl cellulose and crosslinking are poly- for 18g disintegrants
The mixture of vinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2:1),
5g lubricants (superfine silica gel powder), 1g corrigents (Sucralose)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 12
(4), solid dispersions are prepared
5g levo-oxiracetams in 250mL acetone, stir 5~25min, with rotation with 10g PLURONICS F87s uniform dissolution
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 5g levo-oxiracetam solid dispersions, and (microcrystalline cellulose and mannitol mix 65g fillers
Close object, wherein microcrystalline cellulose：Weight ratio=3 of mannitol:1), (low-substituted hydroxypropyl cellulose and crosslinking are poly- for 24g disintegrants
The mixture of vinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2:1),
5g lubricants (superfine silica gel powder), 1g corrigents (Sucralose)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Embodiment 13
(1) preparation of solid dispersions:
By 12g levo-oxiracetams and 12g beta-cyclodextrins uniform dissolution in 95% ethyl alcohol 300mL, stirring 20~
22min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Levo-oxiracetam solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (12g) that step (1) sieving obtains are added in into filler microcrystalline cellulose
60g, 40~50% disintegrant (disintegrant be sodium carboxymethyl starch 22g) are wetting agent with absolute ethyl alcohol, wet granulation mistake
100 mesh sieves, 30~45 DEG C of dryings, whole grain add in remaining disintegrant, corrigent (acesulfame potassium 1g), lubricant (talcum powder 5g), pressure
Piece is made.
Embodiment 14
(1) preparation of solid dispersions:
By 4g levo-oxiracetams and 8g polyvinylpyrrolidones uniform dissolution in 100mL acetone, stirring 20~
22min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Levo-oxiracetam solid dispersions.
(2) preparation of oral disnitegration tablet:
By the obtained levo-oxiracetam solid dispersions (4g) of step (1) sieving add in filler (cornstarch 50g and
The mixture of medicinal calcium carbonate 20g), 40~50% disintegrant (croscarmellose sodium), be moistening with absolute ethyl alcohol
Agent, wet granulation cross 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant, corrigent (essence 0.2g), lubricant
(magnesium stearate 1.8g), it is tabletted.
Embodiment 15
(1) preparation of solid dispersions:
By 3g levo-oxiracetams and 5g PLURONICS F87s uniform dissolution in 80mL dichloromethane, stirring 20~
22min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Levo-oxiracetam solid dispersions.
(2) preparation of oral disnitegration tablet:
By the obtained levo-oxiracetam solid dispersions (3g) of step (1) sieving add in filler (amylum pregelatinisatum),
40~50% disintegrant (crosslinked polyvinylpyrrolidone) is wetting agent with absolute ethyl alcohol, and wet granulation crosses 100 mesh sieves, 30
~45 DEG C of dryings, whole grain add in remaining disintegrant, corrigent (xylitol 0.5g), lubricant (superfine silica gel powder 1.5g), are pressed into
Piece.
Embodiment 16
(1) preparation of solid dispersions:
By 3g levo-oxiracetams and 5g lactose uniform dissolution in 80mL ethyl acetate, 20~22min is stirred, with rotation
Evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get levo-oxiracetam
Solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (3g) that step (1) sieving obtains are added in into filler (microcrystalline cellulose 50g
With the mixture of cornstarch 20g), 40~50% disintegrant (low-substituted hydroxypropyl cellulose), be moistening with absolute ethyl alcohol
Agent, wet granulation cross 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant, corrigent (Sucralose 0.5g), profit
Lubrication prescription (superfine silica gel powder 1.5g), it is tabletted.
Embodiment 17
(1) preparation of solid dispersions:
By 3g levo-oxiracetams and 5g hydroxypropyl celluloses uniform dissolution in 80mL absolute ethyl alcohols, stirring 20~
22min, with Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, cross 100 mesh sieves to get
Levo-oxiracetam solid dispersions.
(2) preparation of oral disnitegration tablet:
By the obtained levo-oxiracetam solid dispersions (3g) of step (1) sieving add in filler (microcrystalline cellulose),
40~50% disintegrant (mixture of dried starch 20g and crosslinked polyvinylpyrrolidone 5g), is wetting agent with absolute ethyl alcohol,
Wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegrant, corrigent (Aspartame 0.5g), lubrication
Agent (hydrogenated vegetable oil 1.5g), it is tabletted.
Embodiment 18
(1) preparation of solid dispersions:
By 4g levo-oxiracetams and 6g succinic acids uniform dissolution in 100mL absolute ethyl alcohols, 20~22min is stirred, is used
Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get left-handed Aura
Western smooth solid dispersions.
(2) preparation of oral disnitegration tablet:
The levo-oxiracetam solid dispersions (4g) that step (1) sieving obtains are added in into filler (amylum pregelatinisatum 48g
With the mixture of mannitol 20g), 40~50% disintegrant (low-substituted hydroxypropyl cellulose 19g and crosslinked polyethylene pyrrolidines
The mixture of ketone 6g), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining
Disintegrant, corrigent (Aspartame 0.5g), lubricant (superfine silica gel powder 2.5g), it is tabletted.
Embodiment 19
(1), solid dispersions are prepared
5g levo-oxiracetams in 250mL acetone, stir 5~25min, with rotation with 25g PLURONICS F87s uniform dissolution
Turn evaporimeter recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves to get solid dispersions.
(2), the preparation of oral disnitegration tablet
Oral disnitegration tablet contains 5g levo-oxiracetam solid dispersions, and (microcrystalline cellulose and mannitol mix 69g fillers
Close object, wherein microcrystalline cellulose：Weight ratio=3 of mannitol:1), (low-substituted hydroxypropyl cellulose and crosslinking are poly- for 21g disintegrants
The mixture of vinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2:1),
4g lubricants (superfine silica gel powder), 1g corrigents (Sucralose)；
Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant (disintegrant that sieve
The 40~50% of total amount), it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in surplus
Remaining disintegrant and corrigent and lubricant, it is tabletted.
Comparative example 1
By levo-oxiracetam 4g, amylum pregelatinisatum 48g, mannitol 20g, low-substituted hydroxypropyl cellulose 19g and crosslinking
Polyvinylpyrrolidone 6g physical mixeds are uniform, are wetting agent with absolute ethyl alcohol, and wet granulation crosses 100 mesh sieves, and 30~45 DEG C dry
Dry, whole grain adds in Aspartame 0.5g, superfine silica gel powder 2.5g, tabletted.
Comparative example 2
By levo-oxiracetam 3g, microcrystalline cellulose 38g, pregelatinized starch 32g, sodium carboxymethyl starch 15g and crosslinking carboxylic
Sodium carboxymethylcellulose pyce 10g physical mixeds are uniform, are wetting agent with absolute ethyl alcohol, and wet granulation crosses 100 mesh sieves, and 30~45 DEG C dry
Dry, whole grain adds in magnesium stearate 2g, tabletted.
2nd, quality evaluating method
Experiment 1：Into graininess and compressibility inspection
Material to be measured is made freely to be fallen from the fixed funnel of sustained height, accumulation body is formed on the disk that radius is r,
Until material is overflowed from disk border, the height h of accumulation body is measured, replication 3 times is averaged, labeled as hIt is average, i.e. hIt is average
=(h1+h2+h3)/3 calculate arctan (hIt is average/ r), if arctan (hIt is average/ r) 35 ° of ＜, and 25 ° of ＞, that is, think that particle is equal
It is even, beneficial to industrialized production.It is suppressed with the tablet press machine of same model, by hardness control in the range of 25-40N.Emphasis
It checks hardness, and has seen whether the abnormal conditions such as fragmentation, softening or viscous puckery punching.
Experiment 2：Disintegration time limited checks
2ml water (37 DEG C) is taken to be placed in 5ml test tubes, adds in sample prepared by above-described embodiment, starts timing, until all collapsing
Independent fine particle is shattered into, stops timing, records disintegration time, test tube needs to stand in disintegrating procedue, takes 6 progress every time
Detection, takes its average value.
Experiment 3：Mouthfeel inspection
Healthy volunteer 6 is chosen, sample prepared by above-described embodiment is placed on lingual surface and starts timing, until in the oral cavity
Whole disintegration start-stops stop timing, record disintegration time, and experience slice, thin piece from being placed in mouth to the sensation in oral cavity after complete disintegration,
Such as sweet tea/hardship, grittiness etc. is whether there is.
Experiment 4：Dissolved corrosion inspection
In view of the unpub levo-oxiracetam elution test method in Chinese food Drug Administration official website, it is contemplated that
Physics, chemistry and the biological property of levo-oxiracetam, thus it is speculated that it is absorbed in enteron aisle, and meanwhile it is molten in the saturation of detection bulk pharmaceutical chemicals
Xie Du is relatively low, and in about pH5.6-5.8, saturation solubility is maximum, has pH dependences, and bulk pharmaceutical chemicals are weak acidic drug, therefore
+ 1% tween of pH6.8 acetate buffers (surface) is determined for screening medium, and condition is as follows：
Testing liquid：+ 1% tween of pH6.8 acetate buffers
Paddle rotating speed：50rpm
Experimental liquid volume：900ml.
The evaluation result of above-described embodiment such as following table.
Levo-oxiracetam oral disnitegration tablet prepared by above-described embodiment (2-4,6-8,10-19), in 25 DEG C ± 2 of temperature
DEG C, carry out long-term stable experiment under the conditions of relative humidity 60% ± 10%, respectively March, June, September, December, 18 months five
Time point is detected respectively, and sample property, content, related substance meet regulation；Stability study sample is good in taste, shows sample
Product are good in 18 months effect phase internal stabilities.
Levo-oxiracetam oral disnitegration tablet prepared by the present invention, formula is reasonable, and it is strong effectively to solve drug hygroscopicity
And causing material in pelletization easily agglomerating, material is sticked in granulation pot wall, causes the non-uniform technical problem of particle, wet method
Particle fine uniform after granulation, angle of repose is preferable into graininess and compressibility between 25~35, and the hardness of the disintegrated tablet of preparation exists
30~40N, the basic disintegration of 30s disintegrations is complete in oral cavity, in good taste, no grittiness, 15min interior energies dissolution more than 80%, no
Special producing condition is needed, has production cost low, carries, stores, transports and take convenient feature, improve patient and take
Compliance has higher practical value.
Claims (10)
1. a kind of levo-oxiracetam oral disnitegration tablet contains active ingredient and pharmaceutically acceptable required excipient；It is described
Active ingredient is levo-oxiracetam solid dispersions, and the excipient includes filler, disintegrant, lubricant or/and flavoring
Agent；The levo-oxiracetam oral disnitegration tablet contains levo-oxiracetam solid dispersions 0.8~14%, and filler 55~
70%, disintegrant 8~25%, lubricant 1~5%, corrigent 0.1~1%.
2. oral disnitegration tablet as described in claim 1, it is characterised in that：The levo-oxiracetam solid dispersions are by 1 part
Levo-oxiracetam, 1~12 part of carrier and 15~80 parts of solvents are made by solvent method；The carrier for succinic acid, beta-cyclodextrin,
The mixing of one or more of Macrogol 6000, polyvinylpyrrolidone, lactose, PLURONICS F87, hydroxypropyl cellulose；
The solvent is the mixing of one or more of absolute ethyl alcohol, 95% ethyl alcohol, acetone, dichloromethane, ethyl acetate.
3. oral disnitegration tablet as claimed in claim 2, it is characterised in that：The levo-oxiracetam solid dispersions are by 1 part
Levo-oxiracetam, 1~8 part of succinic acid and 15~50 parts of absolute ethyl alcohols are made by solvent method.
4. such as claim 1-3 any one of them oral disnitegration tablets, it is characterised in that：The filler for cornstarch, can
The mixing of one or more of pressure property starch, microcrystalline cellulose, medicinal calcium carbonate, mannitol；The disintegrant is dried starch, carboxylic
One kind in methyl starch sodium, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, croscarmellose sodium or
Several mixing；The lubricant is the mixing of one or more of magnesium stearate, superfine silica gel powder, talcum powder, hydrogenated vegetable oil；Institute
Corrigent is stated as the mixing of one or more of Sucralose, xylitol, acesulfame potassium, Aspartame, essence.
5. oral disnitegration tablet as claimed in claim 4, it is characterised in that：The filler mixes for amylum pregelatinisatum and mannitol
Close object, wherein amylum pregelatinisatum：Weight ratio=1~3 of mannitol:1；The disintegrant is low-substituted hydroxypropyl cellulose and friendship
Join the mixture of polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：The weight ratio of crosslinked polyvinylpyrrolidone is 2
~5:1.
6. oral disnitegration tablet as claimed in claim 4, it is characterised in that：The filler is amylum pregelatinisatum, microcrystalline cellulose
The mixture of element and mannitol, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1~2 of mannitol:2~3：1；It is described
Disintegrant is low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, wherein low substituted hydroxy-propyl fiber
Element：The weight ratio of crosslinked polyvinylpyrrolidone is 1~3:1.
7. oral disnitegration tablet as claimed in claim 5, it is characterised in that：The levo-oxiracetam oral disnitegration tablet, contains
Active ingredient and pharmaceutically acceptable required excipient；The active ingredient is levo-oxiracetam solid dispersions, described
Excipient includes filler, disintegrant, lubricant or/and corrigent；The levo-oxiracetam solid dispersions are left-handed by 1 part
Oxiracetam, 1~8 part of succinic acid and 20~50 parts of absolute ethyl alcohols are made by solvent method；The filler for amylum pregelatinisatum and
Mannitol mixture, wherein amylum pregelatinisatum：Weight ratio=1~3 of mannitol:1；The disintegrant is fine for low substituted hydroxy-propyl
The mixture of dimension element and crosslinked polyvinylpyrrolidone, wherein low-substituted hydroxypropyl cellulose：Crosslinked polyvinylpyrrolidone
Weight ratio is 2~5:1；The lubricant is superfine silica gel powder；The corrigent is Sucralose or Aspartame.
8. oral disnitegration tablet as claimed in claim 6, it is characterised in that：The levo-oxiracetam oral disnitegration tablet, contains
Active ingredient and pharmaceutically acceptable required excipient；The active ingredient is levo-oxiracetam solid dispersions, described
Excipient includes filler, disintegrant, lubricant or/and corrigent；The levo-oxiracetam solid dispersions are left-handed by 1 part
Oxiracetam, 1~8 part of succinic acid and 20~40 parts of absolute ethyl alcohols are made by solvent method；The filler is amylum pregelatinisatum, micro-
Crystalline cellulose and mannitol mixture, wherein amylum pregelatinisatum：Microcrystalline cellulose：Weight ratio=1~2 of mannitol:2~3：1；
The disintegrant is low-substituted hydroxypropyl cellulose and the mixture of crosslinked polyvinylpyrrolidone, and wherein low substituted hydroxy-propyl is fine
Dimension element：The weight ratio of crosslinked polyvinylpyrrolidone is 1~3:1；The lubricant is superfine silica gel powder；The corrigent is A Si
Ba Tian.
9. the preparation method of levo-oxiracetam oral disnitegration tablet as described in claim any one of 1-8, using following steps：
Prepare solid dispersions
Levo-oxiracetam in solvent, stirs 5~25min with carrier uniform dissolution, and recycling design dry, pulverize, and crosses 100
Mesh sieve is to get solid dispersions；
The preparation of oral disnitegration tablet
By obtained levo-oxiracetam solid dispersions addition filler, 30~60% disintegrant that sieve（Disintegrant total amount
30~60%）, it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegration
Agent and corrigent and lubricant, it is tabletted.
10. oral disnitegration tablet as claimed in claim 9, it is characterised in that：The system of the levo-oxiracetam oral disnitegration tablet
Preparation Method, using following steps：
Prepare solid dispersions
1 part of levo-oxiracetam and 1~8 part of succinic acid uniform dissolution stir 5~25min in 20~50 parts of absolute ethyl alcohols, use
Rotary Evaporators recycling design, until being dripped there is no liquid, naturally dry crushes, and crosses 100 mesh sieves and disperses to get solid
Body；
（2）, oral disnitegration tablet preparation
Oral disnitegration tablet contains levo-oxiracetam solid dispersions 0.8~14%, filler 55~70%, disintegrant 8~25%,
Lubricant 1~5%, corrigent 0.1~1%；Specifically preparation process is：
By obtained levo-oxiracetam solid dispersions addition filler, 40~50% disintegrant that sieve（Disintegrant total amount
40~50%）, it is wetting agent with absolute ethyl alcohol, wet granulation crosses 100 mesh sieves, 30~45 DEG C of dryings, and whole grain adds in remaining disintegration
Agent and corrigent and lubricant, it is tabletted.
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Citations (5)
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|---|---|---|---|---|
| CN1555794A (en) * | 2004-01-02 | 2004-12-22 | 肖广常 | Orazitan dispersion tablet and its preparation method |
| KR20090098325A (en) * | 2008-03-14 | 2009-09-17 | 엔자이텍 주식회사 | New Production Process of Racemic or Optically Pure (S) -Oxyracetam |
| 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 |
| CN102617437A (en) * | 2012-04-10 | 2012-08-01 | 南京优科生物医药研究有限公司 | Novel crystal formations of levogyration oxiracetam and preparation method thereof |
| CN105434376A (en) * | 2014-08-29 | 2016-03-30 | 武汉光谷人福生物医药有限公司 | Meisuoshuli orally disintegrating tablet and preparation method thereof |
-
2016
- 2016-11-11 CN CN201610995917.9A patent/CN108066292A/en not_active Withdrawn
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1555794A (en) * | 2004-01-02 | 2004-12-22 | 肖广常 | Orazitan dispersion tablet and its preparation method |
| KR20090098325A (en) * | 2008-03-14 | 2009-09-17 | 엔자이텍 주식회사 | New Production Process of Racemic or Optically Pure (S) -Oxyracetam |
| 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 |
| CN102617437A (en) * | 2012-04-10 | 2012-08-01 | 南京优科生物医药研究有限公司 | Novel crystal formations of levogyration oxiracetam and preparation method thereof |
| CN105434376A (en) * | 2014-08-29 | 2016-03-30 | 武汉光谷人福生物医药有限公司 | Meisuoshuli orally disintegrating tablet and preparation method thereof |
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Application publication date: 20180525 |