CN106822055A - A kind of Oxiracetam pelliculae pro cavo oris and preparation method thereof - Google Patents
A kind of Oxiracetam pelliculae pro cavo oris and preparation method thereof Download PDFInfo
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- CN106822055A CN106822055A CN201510903294.3A CN201510903294A CN106822055A CN 106822055 A CN106822055 A CN 106822055A CN 201510903294 A CN201510903294 A CN 201510903294A CN 106822055 A CN106822055 A CN 106822055A
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- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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Abstract
A kind of Oxiracetam pelliculae pro cavo oris, it is obtained by including the raw material including Oxiracetam, filmogen and filler and plasticizer, with a small amount of saliva is that can dissolve in oral cavity, medication by being not required to water delivery service, medication is convenient, it is difficult to spue after being adhered on tongue, is adapted to the old man of dysphagia, and by mucosal absorption, avoid head and cross elimination effect, bioavilability is improve, pharmaceutical dosage is reduced, so as to reduce drug side-effect.Preparation method of the present invention is simple, and process costs are low, is adapted to large-scale production.
Description
Technical field
The present invention relates to Oxiracetam, and in particular to a kind of Oxiracetam pelliculae pro cavo oris and preparation method thereof.
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：
Since being put on market from it, worked well due to it, safe, indication scope is wide, medicine phase
Interaction is few and the low feature of toxicity, is always to treat the leading products in anti-dementia agent, injection,
Capsule, tablets and other formulations develop listing in succession.
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.
Pelliculae pro cavo oris is a kind of oral administration solid quick-release novel form of increasingly extensive application abroad in recent years, by
Have without drinking-water in it, the unique distinction that can be rapidly dissolved in oral cavity makes it possess various advantages,
It is particularly suited for gerontal patient.Although pelliculae pro cavo oris has many advantages, its filmogen and preparation
The limitation of technology and cause drugloading rate low, the vertical intensity of disintegration time and anti-tensile is difficult to control, and when most
The problems such as time needs taste masking, constrains the development and application of pelliculae pro cavo oris.
The content of the invention
It is an object of the invention to provide a kind of Oxiracetam pelliculae pro cavo oris, the film chemically and physically property
Matter stabilization, hardness is moderate, and drugloading rate is higher, and disintegration time is short.
It is a further object of the present invention to provide the preparation method of above-mentioned Oxiracetam pelliculae pro cavo oris, the method
It is simple to operate, it is not necessary to special installation, it is adapted to industrialized production.
Number of the present invention unless otherwise specified, is weight portion.
The object of the present invention is achieved like this：
A kind of Oxiracetam pelliculae pro cavo oris, by including Oxiracetam, filmogen, filler and plasticising
Agent is obtained in interior raw material by following proportioning：
Above-mentioned number is weight portion.
Above-mentioned filmogen be selected from ethyl cellulose, sodium alginate, HPMC, pectin,
One or more in acrylate, sodium carboxymethylcellulose, PVP-vinyl acetate or amylopectin
Combination.
Above-mentioned plasticizer be selected from propane diols, glycerine, dibutyl phthalate, triethyl citrate,
One or more combination in glyceryl triacetate, PEG400 and PEG600.
Above-mentioned filler is selected from microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, friendship
One or more combination in connection sodium carboxymethylcellulose.
Inventor has found that the selection of filmogen is for Oxiracetam pelliculae pro cavo oris in R＆D process
Succeeding, it is most important to prepare, and selection is incorrect to occur that film forming is poor, outward appearance is bad, disintegration time is long
Etc. problems.Research shows, using particular types and the filmogen of consumption, thickness can be obtained
Moderate, satisfactory mechanical property and the shorter Oxiracetam pelliculae pro cavo oris of disintegration time.
It is preferred that
A kind of Oxiracetam pelliculae pro cavo oris, by including 1-20 parts of Oxiracetam, 35-70 parts of filmogen,
5-30 parts of plasticizer and 5-30 parts of filler are obtained；The filmogen is ethyl cellulose.
Inventor also found in further research, be prepared using ethyl cellulose as filmogen
During Oxiracetam pelliculae pro cavo oris, still there may be that film is inter-adhesive, the situation such as matter is soft.
On the basis of many experiments, inventor has found to be solved using suitable plasticizer species and consumption
State problem.
It is preferred that
A kind of Oxiracetam pelliculae pro cavo oris, by including 1-20 parts of Oxiracetam, 35-65 parts of filmogen,
5-25 parts of plasticizer and 5-30 parts of filler are obtained in interior raw material；The filmogen is ethyl cellulose
Element；The plasticizer is glycerine or propane diols.
More preferably：
A kind of Oxiracetam pelliculae pro cavo oris, by including 1-20 parts of Oxiracetam, 40-65 parts of ethyl cellulose
Element, 10-25 parts of glycerine and 5-30 parts of filler are obtained in interior raw material.
In order to increase the use of the dissolution rate of Oxiracetam pelliculae pro cavo oris, above-mentioned glycerine and ethyl cellulose
Amount preferably glycerine：Ethyl cellulose=1:3~4.
The disintegration time of patient adaptability and pelliculae pro cavo oris is taken into account, above-mentioned Oxiracetam pelliculae pro cavo oris
Preferably 80~120 μm, more preferably 100~110 μm of thickness.
The preparation method of above-mentioned Oxiracetam pelliculae pro cavo oris, adopts and is prepared by the following steps：
1) filmogen is dissolved in absolute ethyl alcohol and forms homogeneous viscous liquid, be subsequently adding plasticizer and mix
Even formation material I；
2) Oxiracetam and filler are mixed, carries out dispersion with absolute ethyl alcohol and form material II；
3) material II is mixed with material I, stirs 30-180min, formed Oxiracetam bubble-free and mix
Outstanding viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 45~
95 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Specifically,
A kind of preparation method of Oxiracetam pelliculae pro cavo oris, using following steps：
35-70 parts of filmogen is dissolved in absolute ethyl alcohol and forms homogeneous viscous liquid, be subsequently adding 5-30
Part plasticizer is simultaneously mixed and forms material I；
1-20 parts of Oxiracetam, 5-30 parts of filler and 2-5 parts of flavouring are mixed, absolute ethyl alcohol is used
Carry out dispersion and form material II；
3) material II is mixed with material I, stirs 30-180min, formed Oxiracetam bubble-free and mix
Outstanding viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 45~
95 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Wherein,
Step 1) and step 2) in absolute ethyl alcohol consumption by those of ordinary skill in the art according to reality
It needs to be determined that.
Above-mentioned steps 3) in stir speed (S.S.) be 400r/min~800r/min, mixing time is preferred
60min~120min.
Above-mentioned steps 4) in be cut into according to needed for shapes and sizes cut.
A kind of levo-oxiracetam pelliculae pro cavo oris, by 1-20 parts of levo-oxiracetam, 30-80 parts of film forming
Material, 5-30 part filler and 5-30 parts of plasticizer are obtained, and the number is weight portion.
Above-mentioned filmogen be selected from sodium alginate, HPMC, ethyl cellulose, pectin,
One or more in acrylate, sodium carboxymethylcellulose, PVP-vinyl acetate or amylopectin
Combination.
Above-mentioned plasticizer be selected from propane diols, glycerine, dibutyl phthalate, triethyl citrate,
One or more combination in glyceryl triacetate, PEG400 and PEG600.
Above-mentioned filler is selected from microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, friendship
One or more combination in connection sodium carboxymethylcellulose.
Inventor has found that the selection of filmogen is for levo-oxiracetam oral film in R＆D process
The successful of agent prepares most important, selects incorrect when occurring that film forming is poor, outward appearance is bad, being disintegrated
Between the problems such as long.Inventor also found in further research, prepare levo-oxiracetam mouthful
During the film of chamber, still there may be that film is inter-adhesive, the situation such as matter is soft.
It is preferred that
A kind of levo-oxiracetam pelliculae pro cavo oris, by 1-20 parts of levo-oxiracetam, 35-65 parts of film forming
Material, 5-25 part plasticizer and 5-30 parts of filler are obtained for raw material；The filmogen is fine ethyl
Dimension element；The plasticizer is glycerine or propane diols；The number is weight portion.
More preferably：
A kind of levo-oxiracetam pelliculae pro cavo oris, by 1-20 parts of Oxiracetam, 40-65 parts of ethyl cellulose
Element, 10-25 parts of glycerine and 5-30 parts of filler are obtained.
In order to increase the dissolution rate of levo-oxiracetam pelliculae pro cavo oris, above-mentioned glycerine and ethyl cellulose
Consumption preferably glycerine：Ethyl cellulose=1:3~4.
Take into account the disintegration time of patient adaptability and pelliculae pro cavo oris, above-mentioned levo-oxiracetam oral film
Preferably 80~120 μm, more preferably 100~110 μm of the thickness of agent.
The preparation method of above-mentioned levo-oxiracetam pelliculae pro cavo oris, adopts and is prepared by the following steps：
1) filmogen is dissolved in purified water and forms homogeneous viscous liquid, be subsequently adding plasticizer and mix
Form material I；
2) levo-oxiracetam and filler are mixed, carries out dispersion with purified water and form material II；
3) material II is mixed with material I, stirs 30-180min, form levo-oxiracetam without gas
Bubble suspension viscous fluid；
4) by step 3) obtained in levo-oxiracetam bubble-free suspension viscous fluid cast on mould, in
45~95 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product levo-oxiracetam pelliculae pro cavo oris.
Specifically,
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
35-70 parts of filmogen is dissolved in purified water and forms homogeneous viscous liquid, be subsequently adding 5-30
Part plasticizer is simultaneously mixed and forms material I；
1-20 parts of levo-oxiracetam, 5-30 parts of filler and 2-5 parts of flavouring are mixed, with purifying
Water carries out dispersion and forms material II；
3) material II is mixed with material I, stirs 30-180min, form levo-oxiracetam without gas
Bubble suspension viscous fluid；
4) by step 3) obtained in levo-oxiracetam bubble-free suspension viscous fluid cast on mould, in
45~95 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product levo-oxiracetam pelliculae pro cavo oris.
Wherein,
Step 1) and step 2) in purified water consumption by those of ordinary skill in the art according to actual need
Determine.
Above-mentioned steps 3) in stir speed (S.S.) be 400r/min~800r/min, mixing time is preferred
60min~120min.
Above-mentioned steps 4) in be cut into according to needed for shapes and sizes cut.
The invention has the advantages that：
1st, Oxiracetam pelliculae pro cavo oris of the present invention or levo-oxiracetam pelliculae pro cavo oris are used few in oral cavity
Amount saliva is that can dissolve, and medication by being not required to water delivery service, medication is convenient.
2nd, Oxiracetam pelliculae pro cavo oris of the present invention or levo-oxiracetam pelliculae pro cavo oris appearance uniform are complete,
Uniform color, thickness is consistent, physics and stable chemical nature, and disintegration time is short, and dissolution rate is fast,
Work rapid.
3rd, after Oxiracetam pelliculae pro cavo oris of the present invention or levo-oxiracetam pelliculae pro cavo oris are adhered on tongue
It is difficult to spue, is adapted to the old man of dysphagia, and by mucosal absorption, it is to avoid first mistake eliminates effect
Should, bioavilability is improve, pharmaceutical dosage is reduced, so as to reduce drug side-effect.
4th, filming performance, outward appearance and the disintegration time to take into account pelliculae pro cavo oris of the invention, meticulously selection is special
The ethyl cellulose or ethyl cellulose of consumption are determined as filmogen, make obtained Oxiracetam oral cavity
Film or levo-oxiracetam pelliculae pro cavo oris thickness is moderate, satisfactory mechanical property and disintegration time is shorter.
5th, the present invention is combined with specific filmogen with particular types with the plasticizer of consumption, so as to have
Effect solves that film is inter-adhesive, the technical problem such as matter is soft, and to realize make obtained Oxiracetam mouthful
Chamber film or levo-oxiracetam pelliculae pro cavo oris demolding performace are good, and hardness is moderate, and mechanical performance is high, collapses
The solution time is short, and being both not in that hardness is excessive is easy to be broken or increase disintegration time, is also unlikely to mouth
Chamber film is excessively soft, and extending causes dosage to be forbidden.
6th, preparation method of the present invention is simple, and process costs are low, is adapted to large-scale production.
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 Oxiracetam raw material (content
99.8%, Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. provides, and lot number is：20140917)；It is left
Rotation Oxiracetam raw material (content 99.9%, Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. provides, batch
Number it is：20150317) Hydroxypropyl methylcellulose (HPMC, Dow Chemical company, specification E5)；
Hydroxypropylcellulose (HPC, Ashland companies of the U.S., specification LF)；Ethyl cellulose (Shandong good fortune
Rui Da bio tech ltd)；(the Hunan China limited public affairs of day pharmacy of polyethylene glycol (PEG) 400
Department)；Glycerine, absolute ethyl alcohol (Hu'nan Erkang Pharmaceutical Co., Ltd.)；Triethyl citrate (TEC,
Bangbu Fengyuan Medicine Sci-Tech Development Co., Ltd)；It is low-substituted hydroxypropyl cellulose (L-HPC), pre-
Gelling starch (Anhui Shanhe Medicinal Subsidiary Material Co., Ltd.)；Microcrystalline cellulose (MCC, Germany
JRS companies, specification VIVAPUR 101)；Acetonitrile, methyl alcohol are chromatographically pure, and other reagents are analysis
It is pure.N is the Oxiracetam pelliculae pro cavo oris piece number for determining in embodiment.
Embodiment 1
A kind of preparation method of Oxiracetam pelliculae pro cavo oris, using following steps：
1) 40-65 parts of ethyl cellulose is dissolved in absolute ethyl alcohol and forms homogeneous viscous liquid, be subsequently adding
10-25 parts of glycerine and mixing form material I；
2) 1-20 parts of Oxiracetam, 5-30 parts of filler are mixed, dispersion shape is carried out with absolute ethyl alcohol
Into material II；
3) material II is mixed with material I, is stirred with the stir speed (S.S.) of 500r/min~800r/min
60min~120min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 55~
90 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Embodiment 2
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) 35-60 parts of ethyl cellulose is dissolved in purified water and forms homogeneous viscous liquid, be subsequently adding
15-30 parts of propane diols and mixing form material I；
2) 1-20 parts of levo-oxiracetam, 5-30 parts of filler are mixed, is disperseed with purified water
Form material II；
3) material II is mixed with material I, is stirred with the stir speed (S.S.) of 500r/min~700r/min
70-130min, forms levo-oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in levo-oxiracetam bubble-free suspension viscous fluid cast on mould, in
45~85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product levo-oxiracetam pelliculae pro cavo oris.
Embodiment 3
1) ethyl cellulose is dissolved in absolute ethyl alcohol and forms homogeneous viscous liquid, be subsequently adding glycerine and mix
Even formation material I；
2) Oxiracetam and microcrystalline cellulose are mixed, carries out dispersion with absolute ethyl alcohol and form material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 80min~90min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 72~
75 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Embodiment 4
1) ethyl cellulose is dissolved in 50ml absolute ethyl alcohols and forms homogeneous viscous liquid, be subsequently adding sweet
Oil and mix form material I；
2) Oxiracetam and microcrystalline cellulose are mixed, dispersion formation is carried out with 20ml absolute ethyl alcohols
Material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 90min~100min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 75~
90 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Embodiment 5
1) ethyl cellulose is dissolved in and homogeneous viscous liquid is formed in 50mL purified waters, be subsequently adding the third two
Alcohol and mixing form material I；
2) levo-oxiracetam and pregelatinized starch are mixed, dispersion formation is carried out with 35mL purified waters
Material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 70min~80min, forms levo-oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in levo-oxiracetam bubble-free suspension viscous fluid cast on mould,
In 72~85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product levo-oxiracetam pelliculae pro cavo oris.
Embodiment 6
1) ethyl cellulose is dissolved in 50 parts of absolute ethyl alcohols and forms homogeneous viscous liquid, be subsequently adding third
Glycol and mixing form material I；
2) Oxiracetam and low substitution ethyl cellulose are mixed, is disperseed with 30 parts of absolute ethyl alcohols
Form material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 70min~80min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 72~
85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Comparative example 1
1) 50 parts of sodium alginates are dissolved in 50 parts of absolute ethyl alcohols and form homogeneous viscous liquid, be subsequently adding
20 parts of propane diols and mixing form material I；
2) the low substitution ethyl cellulose of 15 parts of Oxiracetams and 20 parts is mixed, with 30 parts of anhydrous second
Alcohol carries out dispersion and forms material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 70min~80min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 72~
85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Comparative example 2
1) 50 parts of sodium alginates are dissolved in 50 parts of absolute ethyl alcohols and form homogeneous viscous liquid, be subsequently adding
20 parts of dibutyl phthalates and mixing form material I；
2) 15 parts of Oxiracetams, 20 parts low substitution ethyl celluloses and 5 parts of xylitols are mixed, is used
30 parts of absolute ethyl alcohols carry out dispersion and form material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 70min~80min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 72~
85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Comparative example 3
1) 50 parts of ethyl celluloses are dissolved in 50 parts of absolute ethyl alcohols and form homogeneous viscous liquid, Ran Houjia
Enter 20 parts of glyceryl triacetates and mixing forms material I；
2) 15 parts of Oxiracetams, 20 parts low substitution ethyl celluloses and 5 parts of xylitols are mixed, is used
30 parts of absolute ethyl alcohols carry out dispersion and form material II；
3) material II is mixed with material I, is stirred, stir speed (S.S.) is 500r/min~600r/min,
Mixing time is 70min~80min, forms Oxiracetam bubble-free suspension viscous fluid；
4) by step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 72~
85 DEG C of dryings, room temperature cooling, skinning, cutting obtains final product Oxiracetam pelliculae pro cavo oris.
Pelliculae pro cavo oris 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 Oxiracetam pelliculae pro cavo oris is determined using HPLC methods.Chromatographic condition：Chromatographic column
InertSustain C18 posts (4.6mm × 250mm, 5 μm)；0.02mol/L sodium dihydrogen phosphates are molten
Liquid is mobile phase, Detection wavelength 210nm；30 DEG C of column temperature；Flow velocity 0.6ml/min；Sample size 20
μl.Oxiracetam concentration c is good with peak area A linear relationships in the range of 0.5~100 μ g/ml,
Linear equation is A=3.7381 × 104c+3.7513×103, R2=0.9998.This law in a few days RSD
It is 0.60% (n=6), average recovery rate is 100.4% (n=9), can be directly used for Oxiracetam
The analysis of pelliculae pro cavo oris is determined.Levo-oxiracetam pelliculae pro cavo oris can also be directly used in similar approach
Analysis determine.
Embodiment 3-6 and comparative example 1-3 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 Oxiracetam film/levo-oxiracetam film thickness evenness preferably, possesses suitable
Suppleness and tensile property, weight differential and uniformity of dosage units meet Chinese Pharmacopoeia version two in 2010
Regulation.Film A+1.80 × S is respectively less than 4, mouth obtained in comparative example 1-3 obtained in embodiment 3-6
Chamber film A+1.80 × S is more 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 3-6 and comparative example 1-3 is：
Film disintegration time obtained in embodiment 3-6 is respectively less than 30s, oral film obtained in comparative example 1-3
Agent disintegration time is in more than 45s.
Dissolution in vitro is tested
Dissolution determination uses slurry processes, determine embodiment 3-6 and comparative example 1-3 pelliculae pro cavo oris it is molten
Out-degree, 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 film of embodiment 3-6 starts disintegration in 10s, and drug release is rapid, 5min
Interior dissolution is complete more than the basic dissolutions of 85%, 10min；Pelliculae pro cavo oris 10s obtained in comparative example 1-3
Interior to start disintegration, drug release is rapid, in 5min dissolution more than dissolution in 70%, 10min more than 90%,
The basic dissolutions of 20min are complete；
Comparative example 1 investigates filmogen to influence of the invention (with reference to reference to embodiment 6), experiment
When display sodium alginate is as filmogen, the disintegration time of the film of preparation is more than 40s, dissolution rate
It is slightly slower as filmogen than ethyl cellulose.Inventor is also with other filmogen (pectin, propylene
Acid esters, sodium carboxymethylcellulose, amylopectin, PVP-vinyl acetate) carried out with reference to comparative example 1
Experiment, as a result shows that acrylate, sodium carboxymethylcellulose and amylopectin are obtained as filmogen
Pelliculae pro cavo oris film forming and outward appearance preferably, but its disintegration time is more long；Pectin and PVP-acetic acid second
Pelliculae pro cavo oris mechanical performance is poor obtained in alkene, and demolding performace ratio is not as good as mouth obtained in ethyl cellulose
Chamber film.
Embodiment 7-14
Embodiment 7-14 is operated by following parameter with reference to the step of embodiment 4-6：
The property of pelliculae pro cavo oris with reference to obtained in above method measurement embodiment 7-14.
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
Prepared film thickness evenness preferably, possesses suitable suppleness and tensile property, weight
Difference and uniformity of dosage units meet the Chinese Pharmacopoeia regulation of version two in 2010.
Disintegration time, specifically see the table below：
Pelliculae pro cavo oris disintegration properties are good obtained in embodiment 7-14.
Dissolution in vitro is tested, and specifically be see the table below
Experiment display pelliculae pro cavo oris favorable solubility.
To sum up, Oxiracetam pelliculae pro cavo oris/levo-oxiracetam pelliculae pro cavo oris appearance uniform of the present invention is complete
Whole, uniform color, thickness is consistent, physics and stable chemical nature, and disintegration time is short, dissolution rate
Hurry up, work rapid.
Claims (8)
1. a kind of Oxiracetam pelliculae pro cavo oris, is obtained by including the raw material including Oxiracetam, filmogen, filler and plasticizer by following weight：
Oxiracetam
1-20 parts
Ethyl cellulose
35-70 parts
Plasticizer
5-30 parts
Filler
5-30 parts.
2. pelliculae pro cavo oris as claimed in claim 1, it is characterised in that：The plasticizer is selected from the one or more combination in propane diols, glycerine, dibutyl phthalate, triethyl citrate, glyceryl triacetate, PEG400 and PEG600.
3. pelliculae pro cavo oris as claimed in claim 1, it is characterised in that：It is obtained by including the raw material including 1-20 parts of Oxiracetam, 35-65 parts of filmogen, 5-25 parts of plasticizer and 5-30 parts of filler；The filmogen is ethyl cellulose；The plasticizer is glycerine or propane diols.
4. the pelliculae pro cavo oris as described in claim any one of 1-3, it is characterised in that：It is obtained by including the raw material including 1-20 parts of Oxiracetam, 40-60 parts of ethyl cellulose, 10-25 parts of glycerine and 5-30 parts of filler；The thickness of the Oxiracetam pelliculae pro cavo oris is 80~120 μm.
5. the pelliculae pro cavo oris as described in claim any one of 1-3, it is characterised in that：The filler is selected from the one or more combination in microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, Ac-Di-Sol.
6. pelliculae pro cavo oris as claimed in claim 4, it is characterised in that：The filler is selected from the one or more combination in microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, Ac-Di-Sol.
7. a kind of preparation method of Oxiracetam pelliculae pro cavo oris, it is characterised in that use following steps：
1）35-70 parts of filmogen is dissolved in absolute ethyl alcohol and forms homogeneous viscous liquid, be subsequently adding 5-30 parts of plasticizer and mixing forms material I；
2）1-20 parts of Oxiracetam and 5-30 parts of filler are mixed, dispersion is carried out with absolute ethyl alcohol and is formed material II；
3）Material II is mixed with material I, 30-180min is stirred, Oxiracetam bubble-free suspension viscous fluid is formed；
4）By step 3) obtained in Oxiracetam bubble-free suspension viscous fluid cast on mould, in 45~95 DEG C of dryings, room temperature cooling, skinning, cutting obtain final product Oxiracetam pelliculae pro cavo oris.
8. method as claimed in claim 7, it is characterised in that：The step 3) in stir speed (S.S.) be 400r/min~800r/min, mixing time be 60min~120min.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510903294.3A CN106822055A (en) | 2015-12-07 | 2015-12-07 | A kind of Oxiracetam pelliculae pro cavo oris and preparation method thereof |
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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 CN201510903294.3A patent/CN106822055A/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 |
|---|
| 杨明等: "《药剂学》", 31 August 2014, 中国医药科技出版社 * |
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