CN106822050A - A kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation - Google Patents
A kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation Download PDFInfo
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Abstract
The invention discloses a kind of method for preparing levo-oxiracetam oral quick-dissolving film preparation, levo-oxiracetam, filmogen, plasticizer, saliva stimulant and flavouring are fully ground, are well mixed, by hot melt extruded film forming；There is no the participation of water or organic solvent in preparation process of the present invention, it is to avoid moisture is high in air bubble problem and film caused by there is a problem of due to solvent, is effectively guaranteed the homogeneity of levo-oxiracetam oral quick-dissolving film preparation.
Description
Technical field
The present invention relates to Oxiracetam, and in particular to a kind of hot melt extruded prepares levo-oxiracetam oral cavity
The method of instant film.
Background technology
Oxiracetam (Oxiracetam), chemical entitled Esomeprazole,
It, than the cereboactive drug that Qie Mu company synthesized first in 1974, is a kind of hydroxyl amino to be by Italian SmithKline
Butyric acid (GABOB) derivative, can promote study, strengthen memory, protect the maincenter of damaged nerve cell
Drugs for nervous, its structure is as follows：
CN102552125A discloses it improves the mnemonic learning function of memory and amentia patient；It is also applied for light
Memory and amentia or conduct that the diseases such as moderate vascular dementia, senile dementia and brain trauma cause
Its auxiliary therapy medicine.CN102600130A discloses it is used to treat the new clinical practice of epilepsy.
At present clinically, Oxiracetam mainly has injection, capsule and tablet, for brain damage and causes
Neurological deficit, memory and the treatment of disturbance of intelligence.Display is had been reported that, its levo form compares DL
Body has more preferable curative effect in terms of cognition dysfunction is treated.
CN104069074A discloses a kind of Oxiracetam injection lyophilized formulations, and said preparation is for first by Aura west
It is smooth to form the certain density aqueous solution, it is subsequently adding ethanol lyophilized prepared；The lyophilized formulations are substantially free of
Auxiliary material, redissolution is rapid, quality is good, storage is stable.Such preparation is directly injected into tissue or blood vessel, nothing
Absorption process or absorption process are very short, thus haemoconcentration can rapidly reach peak and play a role；But
It is developed and production process is complicated, and due to the injection aseptic apyrogeneity of requirement, production process is strict, step
It is rapid it is more need appointed condition higher, and in injection medicine generally with molecular state micron order
Solid small particles be dispersed in water, decentralization is very big, and often to produce medicine by high-temperature sterilization
Hydrolysis, oxidation, solids coalescence become big equistability problem.Simultaneously because injection is directly rapid
Into human body, the protection without human body normal physiological barrier, if therefore dosage is improper or inject too fast, or
There is problem in drug quality, be possible to bring harm to patient, or even cause the consequence that cannot be retrieved.
In addition injection pain, can not by patient's self-administer, injection site produce scleroma and intravenous injection draw
Play the problem existed when vascular inflammation is all clinical practice.
CN101732251A discloses a kind of oxiracetam liposome, by Oxiracetam, phosphatide, cholesterol,
Tween 80 and appropriate osmotic pressure regulator and cushioning liquid are obtained；The liposome stability is good, bag
Envelope rate is high, toxic and side effect is small；But liposome preparation complex process, is not suitable for large-scale production；More
For it is important that curative effect of the liposome in human body need further research, the current country rarely has lipid
Body preparation is used for clinic.
CN103494790A discloses a kind of oxiracetam capsule, by xylitol, lubricant and crystal form
Oxiracetam be obtained；Obtained oxiracetam capsule quality stability is significantly improved, preparation technology letter
Single, production cost reduction.CN104739796A discloses a kind of Oxiracetam tablet, by a certain amount of
Oxiracetam, filler, disintegrant, binder and lubricant are obtained；The tablets, carry,
Transport and storage are all more convenient.But in actual clinical, capsule, tablet are choked and cough thing often
Part, and the patient of feeblemindedness is in the majority with the elderly, this kind of patient usually for medicine dysphagia,
Oxiracetam capsule agent, tablet is taken to be inconvenient.
CN1555794A discloses a kind of Orazitan dispersion tablet, by Oxiracetam, disintegrant, lubricant and
Glidant and adhesive are obtained, and dispersed fine particle can be promptly disintegrated into after the medicine is oral, are had
Absorbed beneficial to drug-eluting；It is convenient to take, it is oral after the dispersion that can add water, can be also contained in mouth and be suck clothes
Or swallow.Oral dispersable tablet equally exists the problem choked and cough, and suckes and take dispersible tablet, and its action is very slow
Slowly, and there is sand type and bitter taste, be unfavorable for taking.
102670527A discloses a kind of preparation technology of levo-oxiracetam freeze-dried powder, using left-handed Austria
La Xitan, excipient, antiplastering aid and pH adjusting agent are obtained.Freeze-dried powder needs large scale equipment, non-
Produced under often harsh environment, its application is somewhat limited.
Oral quick-dissolving film preparation is a kind of new agent of oral administration solid quick-release of increasingly extensive application abroad in recent years
Type, because it has without drinking-water, the unique distinction that can be rapidly dissolved in oral cavity possesses it many
The advantage of kind, is particularly suited for gerontal patient.Although oral quick-dissolving film preparation has many advantages, its film forming
Material and the limitation of preparation technique and cause drugloading rate low, disintegration time is difficult to control with the vertical intensity of anti-tensile,
And the problems such as need taste masking when most, constrain the development and application of oral quick-dissolving film preparation.
The content of the invention
Levo-oxiracetam oral quick-dissolving film preparation is prepared it is an object of the invention to provide a kind of hot melt extruded
Method, the method is easy to operate, and controllability is high, is adapted to industrialized production.
Percentage of the present invention unless otherwise specified, is mass percent.
The object of the present invention is achieved like this：
A kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation, it is characterised in that
Using following steps：
By the levo-oxiracetam of 2-12%, the filmogen of 84-94%, the plasticizer of 2-12%, 1-5%
Saliva stimulant and 1-3% flavouring mixing after with hot melt film laminator extrude film forming；It is described into membrane material
Material forms sediment selected from pectin, shitosan, hyaluronic acid, ethyl cellulose, sodium carboxymethylcellulose or side chain
One or more combination in powder；The saliva stimulant is ascorbic acid, citric acid, lactic acid, apple
One kind in tartaric acid；The plasticizer be selected from triethyl citrate, triacetic acid propylene glycol ester, glycerine,
One or more combination in propane diols and PEG600；The flavouring be selected from xylitol, Sucralose,
Sucrose, Abbas are sweet, the one or more combination in fructose.
It is logical with high molecular polymer filmogen and other auxiliary materials that above-mentioned hot melt extruded film forming is substantially medicine
The feed zone of the molten film laminator of overheat is sent to hot melt area, and under the control of specific temperature, raw material gradually melts
Change and mix, the mixture of fusing continues through the output of dosage area, pours into the mould of selected proterties, cools down
After form film.
Inventor has found in R＆D process, and it is strong that the levo-oxiracetam oral quick-dissolving film preparation of preparation has
Degree and/or toughness are bad, are easily broken off, and some prolonged disintegrations, solution time is more long, is unfavorable for medicine
Absorption.
An embodiment of the invention,
The method that above-mentioned hot melt extruded prepares levo-oxiracetam, it is characterised in that：By the left-handed Aura of 2-10%
Western smooth, 84-92% filmogen, the plasticizer of 2-10%, the saliva stimulant of 1-4% and 1-3%'s rectifys
Taste agent is fully ground, is well mixed, and hot melt area is sent to by the feed zone for heating film laminator, at 70-95 DEG C
Hot melt, the mixture of fusing continues through the output of dosage area, pours into mould, and film is formed after cooling；
The filmogen is selected from one or more in pectin, shitosan, hyaluronic acid or ethyl cellulose
Combination；The saliva stimulant is the one kind in ascorbic acid, citric acid, lactic acid, malic acid；
The plasticizer is selected from the one kind in triethyl citrate, triacetic acid propylene glycol ester, glycerine, propane diols
Or several combinations；The one kind or several of the flavouring selected from xylitol, Sucralose, Abbas in sweet
Plant combination.
An embodiment of the invention,
A kind of method for preparing levo-oxiracetam oral quick-dissolving film preparation, it is characterised in that using following
Step：
By the levo-oxiracetam of 3-10%, the filmogen of 84-91%, the plasticizer of 3-10%, 2-4%
Saliva stimulant and the flavouring of 1-3% be fully ground, be well mixed, by heating entering for film laminator
Material area is sent to hot melt area, and in 70-95 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, pours
Enter mould, film is formed after cooling；Above-mentioned filmogen is selected from shitosan or hyaluronic acid；Above-mentioned increasing
Modeling agent is selected from triethyl citrate or glycerine.
An embodiment of the invention, a kind of levo-oxiracetam oral quick-dissolving film preparation for preparing
Method, it is characterised in that use following steps：
By the levo-oxiracetam of 5-10%, the hyaluronic acid of 84-89%, the triethyl citrate of 3-8%,
The saliva stimulant of 2-4%, the flavouring of 1-3% is fully ground, it is well mixed after, by heating press mold
The feed zone of machine is sent to hot melt area, and in 70-85 DEG C of hot melt, it is defeated that the mixture of fusing continues through dosage area
Go out, pour into mould, film is formed after cooling.
An embodiment of the invention, a kind of levo-oxiracetam oral quick-dissolving film preparation for preparing
Method, it is characterised in that use following steps：
By the levo-oxiracetam of 3-6%, the shitosan of 88-91%, the glycerine of 3-10%, 2-4% saliva
Stimulant, the flavouring of 1-3% is fully ground, it is well mixed after, be added in hot melt film laminator,
80-90 DEG C of hot melt extruded film forming.
In order to take into account disintegration time and patient adaptability, levo-oxiracetam oral cavity speed prepared by the present invention
The thickness of molten film is advisable with 100~110 μm.
The mixed charging rate of raw material, mould during hot melt extruded of the present invention, output speed is by this area
Technical staff selects or adjusts according to actual needs；The thickness of film enters according to the actual needs with size
Row setting and cutting.
The invention has the advantages that：
Levo-oxiracetam oral quick-dissolving film preparation appearance uniform prepared by the present invention is complete, uniform color, thickness
Unanimously, physics and stable chemical nature, with a small amount of saliva are that can dissolve in oral cavity, are not required to be sent with water
Medication by clothes, medication is convenient.Levo-oxiracetam oral quick-dissolving film preparation prepared by the present invention is on tongue
It is difficult to spue after adhesion, is adapted to the old man of dysphagia, and by mucosal absorption, it is to avoid first mistake
Effect is eliminated, bioavilability is improve, pharmaceutical dosage is reduced, so as to reduce drug side-effect.
Preparation method of the present invention is simple, do not have the participation of water or organic solvent in preparation process, it is to avoid due to
Solvent there is a problem of caused by moisture is high in air bubble problem and film, be effectively guaranteed a left side
Revolve the homogeneity of Oxiracetam oral quick-dissolving film preparation.Film forming to take into account oral quick-dissolving film preparation of the invention
Can, outward appearance and disintegration time, the shitosan or hyaluronic acid of specific consumption are selected meticulously as into membrane material
Material, makes moderate obtained levo-oxiracetam oral quick-dissolving film preparation thickness, satisfactory mechanical property and disintegration
Time is shorter.The present invention is combined with specific filmogen with the plasticizer of particular types and consumption, from
And effectively solve film and be easily broken off, intensity and toughness is bad and prolonged disintegration, solution time compared with
It is long, it is unfavorable for the technical problems such as the absorption of medicine, realizing makes obtained levo-oxiracetam oral cavity speed
Molten film demolding performace is good, and medicine film is soft, not to be broken, the short excellent results of solution time.This hair
Saliva stimulant and flavor enhancement in bright raw material, effectively raise levo-oxiracetam oral instant membrane
Agent melting speed in the oral cavity, and the technical problem of the sand type of film presence is solved, effectively
The compliance that improve film.
Embodiment
In order that the purpose of the present invention and technical scheme are clearer, it is preferable to carry out to of the invention below
Example is described in detail.To illustrate that：Following examples are served only for carrying out further the present invention
Explanation, and it is not intended that limiting the scope of the invention.Those skilled in the art according to
Some nonessential modifications and adaptations that the above of the invention is made belong to protection model of the invention
Enclose.
The present invention is raw materials used to be commercially available prod with reagent.Wherein levo-oxiracetam raw material (content
99.8%, Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. provides, and lot number is：20150211)；Hydroxyl
Third methylcellulose (HPMC, Dow Chemical company, specification E5)；Shitosan (deacetylation
85%, viscosity 100, Shandong Apollo Group Co., Ltd)；(Shaanxi is gloomy not biological for hyaluronic acid
Technology Co., Ltd.)；Polyethylene glycol (PEG) 400 (Hunan Hua pharmaceutical Co. Ltds)；Chinese holly
Rafter triethylenetetraminehexaacetic acid ester (TEC, Bangbu Fengyuan Medicine Sci-Tech Development Co., Ltd)；Acetonitrile, methyl alcohol are color
Spectrum is pure, and other reagents are pure for analysis.Present invention hot melt film laminator is China State Institute of Pharmaceutical Industry's medicine
Thing preparation national project center provides.N is the levo-oxiracetam oral instant membrane for determining in embodiment
Agent piece number.
Embodiment 1
By 6g levo-oxiracetams, 87g hyaluronic acids, 4g triethyl citrates, 2g ascorbic acid,
1g fructose mixes, be fully ground, it is well mixed after, hot melt is sent to by the feed zone for heating film laminator
Area, in 80-85 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, pours into mould, cold
But film is formed afterwards.
Embodiment 2
By 7g levo-oxiracetams, 85g hyaluronic acids, 5g triethyl citrates, 2g citric acids, 1g
The sweet mixing of Abbas, be fully ground, it is well mixed after, heat is sent to by the feed zone for heating film laminator
Melting zone, in 85-90 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, pours into mould, cold
But film is formed afterwards.
Embodiment 3
By 8g levo-oxiracetams, 86g shitosans, 3g glycerine, 2g saliva stimulants, 1g xyloses
Alcohol mixes, be fully ground, it is well mixed after, hot melt area is sent to by the feed zone for heating film laminator,
In 85-90 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, pours into mould, shape after cooling
Film forming agent.
With reference to embodiment 1-3, following examples are prepared：(consumption is weight g) in following table
Embodiment 13
Oral quick-dissolving film preparation property is determined
Assay method
Thickness and quality
Thickness measurement (4 Ge Jiaohe centers) is carried out in the different position of film with calibrator, and it is accurate
Weighed every piece of film quality, calculates average and standard deviation.
Mechanical performance
Weighing film mechanical performance mainly has 3 indexs：Tensile strength, elongation and folding strength.Will
Film cuts into 2.0cm × 3.0cm sizes, every piece of film use tensile testing machine (draw speed for
25mm/min) longitudinal stretching, until film be broken untill, record reading, calculate tensile strength and
Elongation.The same position of film it is folding to its fracture to determine the folding strength of film, with fracture
The logarithm of preceding twofold number of times represents folding strength.
Content
The content of levo-oxiracetam oral quick-dissolving film preparation is determined using HPLC methods.Chromatographic condition：Color
Spectrum post InertSustain C18 posts (4.6mm × 250mm, 5 μm)；0.02mol/L biphosphates
Sodium solution is mobile phase, Detection wavelength 210nm；30 DEG C of column temperature；Flow velocity 0.6ml/min；Sample introduction
Measure 20 μ l.Levo-oxiracetam concentration c is linear with peak area A in the range of 0.5~100 μ g/ml
Relation is good, and linear equation is A=3.7381 × 104c+3.7513×103, R2=0.9998.This
RSD is 0.60% (n=6) in France and Japan, and average recovery rate is 100.4% (n=9), can directly be used
Determined in the analysis of levo-oxiracetam oral quick-dissolving film preparation.
Embodiment 1-7 test results table specific as follows：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Prepared levo-oxiracetam film thickness evenness preferably, possesses suitable suppleness and drawing
Performance is stretched, weight differential and uniformity of dosage units meet the Chinese Pharmacopoeia regulation of version two in 2010.Implement
Film A+1.80 × S obtained in example 1-7 is respectively less than 5.
Disintegration time
Film is put into equipped with 37 DEG C of beakers of purified water 50ml, is vortexed.Visually observe, remember
The disintegration time of film is recorded, each embodiment takes 3 pieces of films and is measured.
The Mean disintegration time of acetonideexample 1-7 is：
Levo-oxiracetam oral quick-dissolving film preparation disintegration time is in below 32s obtained in embodiment 1-7.
Dissolution in vitro is tested
Dissolution determination uses slurry processes, determines the levo-oxiracetam oral quick-dissolving film preparation of embodiment 1-7
Dissolution rate, dissolution medium is water, and dissolution volume is 1000mL, and temperature is 37 DEG C, rotating speed 100rpm.
Result specifically see the table below：
Experiment display：The levo-oxiracetam oral quick-dissolving film preparation of embodiment 1-7 starts in 10s
Disintegration, drug release is rapid, and dissolution is complete more than the basic dissolutions of 85%, 10min in 5min.
The property of oral quick-dissolving film preparation with reference to obtained in above method measurement embodiment 8-12.
Thickness, quality, mechanical performance, content and uniformity of dosage units detection such as following table：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display, the thickness of embodiment 8,9 is uniform, and surface is smooth, possess suitable suppleness and
Preferably, A+1.80 × S is not more than 3.5 for tensile property, weight differential and uniformity of dosage units.Embodiment 10/11
It is comparative example, its surface is smooth, and mechanical property is slightly worse, A+1.80 × S is apparently higher than embodiment 8.It is real
Apply the weight differential of example 12 and uniformity of dosage units is preferable.
Disintegration time, specifically see the table below：
The disintegration time of embodiment 10/11 is most long, and the disintegration time of embodiment 12 is shorter than embodiment 10,
The disintegration time of embodiment 8/9 is not more than 30s.
Dissolution in vitro is tested, and specifically be see the table below
The experiment display favorable solubility of embodiment 8/9, embodiment 10-12 is poor.
In above-mentioned experiment, embodiment 10-12 is comparative example, and embodiment 10 has investigated plasticizer pair
The influence of levo-oxiracetam oral quick-dissolving film preparation is prepared, when experiment display is with PEG600 as plasticizer,
The uniformity of dosage units of the levo-oxiracetam oral quick-dissolving film preparation of preparation is poor, disintegration time and accumulative
Dissolution rate all can be filmogen than hyaluronic acid, and triethyl citrate is that film obtained in plasticizer is poor.
Embodiment 11 has investigated filmogen to influence of the invention, and experiment display is into membrane material with amylopectin
During material, the uniformity of dosage units of the levo-oxiracetam oral quick-dissolving film preparation of preparation is poor, disintegration time with
And accumulative dissolution all can be filmogen than hyaluronic acid, triethyl citrate is that plasticizer or shell are poly-
Sugar is filmogen, and glycerine is poor as film obtained in plasticizer.Inventor has also investigated other simultaneously
Plasticizer (triethyl citrate, triacetic acid propylene glycol ester, glycerine, propane diols or PEG600) with into
Membrane material (pectin, shitosan, hyaluronic acid, ethyl cellulose, sodium carboxymethylcellulose or side chain
Starch) prepare levo-oxiracetam oral quick-dissolving film preparation；When filmogen is hyaluronic acid,
Plasticizer is best triethyl citrate, obtained levo-oxiracetam oral quick-dissolving film preparation medicine film softness,
It is non-breakable；When shitosan is filmogen, glycerine is best as plasticizer, obtained left-handed Aura
Western smooth oral quick-dissolving film preparation medicine film solution time is most short.
To sum up, levo-oxiracetam oral quick-dissolving film preparation appearance uniform of the present invention is complete, uniform color,
Thickness is consistent, physics and stable chemical nature, and disintegration time is short, and dissolution rate is fast, works rapid.
Claims (6)
1. a kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation, it is characterised in that use following steps：
After the flavouring of the levo-oxiracetam of 2-12%, the filmogen of 84-94%, the plasticizer of 2-12%, the saliva stimulant of 1-5% and 1-3% is mixed film forming is extruded with hot melt film laminator；The filmogen is selected from the one or more combination in pectin, shitosan, hyaluronic acid, ethyl cellulose, sodium carboxymethylcellulose or amylopectin；The saliva stimulant is the one kind in ascorbic acid, citric acid, lactic acid, malic acid；The plasticizer is selected from the one or more combination in triethyl citrate, triacetic acid propylene glycol ester, glycerine, propane diols and PEG600；The flavouring is selected from that xylitol, Sucralose, sucrose, Abbas be sweet, the one or more combination in fructose.
2. the method for claim 1, it is characterised in that：The flavouring of the levo-oxiracetam of 2-10%, the filmogen of 84-92%, the plasticizer of 2-10%, the saliva stimulant of 1-4% and 1-3% is fully ground, is well mixed, hot melt area is sent to by the feed zone for heating film laminator, in 70-95 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, mould is poured into, film is formed after cooling；The filmogen is selected from the one or more combination in pectin, shitosan, hyaluronic acid or ethyl cellulose；The saliva stimulant is the one kind in ascorbic acid, citric acid, lactic acid, malic acid；The plasticizer is selected from the one or more combination in triethyl citrate, triacetic acid propylene glycol ester, glycerine, propane diols；One or more combination of the flavouring selected from xylitol, Sucralose, Abbas in sweet.
3. method as claimed in claim 1 or 2, it is characterised in that use following steps：
The flavouring of the levo-oxiracetam of 3-10%, the filmogen of 84-91%, the plasticizer of 3-10%, the saliva stimulant of 2-4% and 1-3% is fully ground, is well mixed, hot melt area is sent to by the feed zone for heating film laminator, in 70-95 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, mould is poured into, film is formed after cooling；Above-mentioned filmogen is selected from shitosan or hyaluronic acid；Above-mentioned plasticizer is selected from triethyl citrate or glycerine.
4. method as claimed in claim 1 or 2, it is characterised in that use following steps：By the levo-oxiracetam of 5-10%, the hyaluronic acid of 84-89%, the triethyl citrate of 3-8%, 2-4% saliva stimulant, the flavouring of 1-3% is fully ground, it is well mixed after, hot melt area is sent to by the feed zone for heating film laminator, in 70-95 DEG C of hot melt, the mixture of fusing continues through the output of dosage area, mould is poured into, film is formed after cooling.
5. method as claimed in claim 1 or 2, it is characterised in that：The thickness of the levo-oxiracetam oral quick-dissolving film preparation of preparation is 100~110 μm.
6. method as claimed in claim 4, it is characterised in that：The thickness of the levo-oxiracetam oral quick-dissolving film preparation of preparation is 100~110 μm.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510891133.7A CN106822050A (en) | 2015-12-07 | 2015-12-07 | A kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510891133.7A CN106822050A (en) | 2015-12-07 | 2015-12-07 | A kind of method that hot melt extruded prepares levo-oxiracetam oral quick-dissolving film preparation |
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| CN106822050A true CN106822050A (en) | 2017-06-13 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid preparation with levo-oxiracetam as active component |
| CN104940174A (en) * | 2015-07-23 | 2015-09-30 | 合肥华方医药科技有限公司 | Preparation method of donepezil oral fast dissolving film |
-
2015
- 2015-12-07 CN CN201510891133.7A patent/CN106822050A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid preparation with levo-oxiracetam as active component |
| CN104940174A (en) * | 2015-07-23 | 2015-09-30 | 合肥华方医药科技有限公司 | Preparation method of donepezil oral fast dissolving film |
Non-Patent Citations (1)
| Title |
|---|
| 陈芳 等: "伏格列波糖口溶膜剂的制备及质量评价", 《中国医药工业杂志》 * |
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Application publication date: 20170613 |