CN106822060A - A kind of levo-oxiracetam pelliculae pro cavo oris and preparation method thereof - Google Patents

A kind of levo-oxiracetam pelliculae pro cavo oris and preparation method thereof Download PDF

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CN106822060A
CN106822060A CN201510904232.4A CN201510904232A CN106822060A CN 106822060 A CN106822060 A CN 106822060A CN 201510904232 A CN201510904232 A CN 201510904232A CN 106822060 A CN106822060 A CN 106822060A
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parts
levo
oxiracetam
filmogen
viscous fluid
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叶雷
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Chongqing Runze Pharmaceutical Co Ltd
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Chongqing Runze Pharmaceutical Co Ltd
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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
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A61K47/38—Cellulose; Derivatives thereof

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Abstract

A kind of levo-oxiracetam pelliculae pro cavo oris, is obtained by levo-oxiracetam, filmogen, filler, plasticizer, sweetener and saliva stimulant；Wherein filmogen is comprising maltodextrin and at least another macromolecule filming material；And another macromolecule filming material is selected from the one or more combination in hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose；Solve pelliculae pro cavo oris and easily occur that matter is soft, filming performance is poor, the technical problems such as the demoulding are difficult to, so as to improve product quality.Preparation method of the present invention is simple, is adapted to industrialized production.

Description

A kind of levo-oxiracetam pelliculae pro cavo oris and preparation method thereof
Technical field
The present invention relates to Oxiracetam, and in particular to a kind of side for preparing levo-oxiracetam pelliculae pro cavo oris Method.
Background technology
Oxiracetam (Oxiracetam) is nootropic agents of new generation, pyrrolidinone compounds (ring GABOB) derivative, Piracetam analog can promote Phosphorylcholine and adjacent acyl monoethanolamine to synthesize, Promote brain metabolism, have stimulation to specific central nervous pathway by blood-brain barrier, improve intelligence And memory.To cerebrovascular disease, brain damage, brain tumor (postoperative), intracranial infection, dementia, cerebral degeneration Disease etc. has good efficacy.Suitable for light moderate vascular dementia, senile dementia and brain trauma The memory caused Deng disease and disturbance of intelligence.Oxiracetam is by Italian SmithKline than Qie Mu company in 1974 Synthesize first, list within 1987, the concentration to remembering especially thinking is more preferable than Piracetam, and poison Property it is smaller, research shows the better efficacy of its levo form (structure is as follows),
CN104069074A discloses a kind of Oxiracetam injection lyophilized formulations, and said preparation is first by Aura The western smooth certain density aqueous solution of formation, is subsequently adding ethanol lyophilized prepared；The lyophilized formulations are substantially not Containing auxiliary material, redissolution is rapid, quality is good, storage is stable.Such preparation is directly injected into tissue or blood vessel, It is very short without absorption process or absorption process, thus haemoconcentration can rapidly reach peak and play a role；But It is that it is developed and production process is complicated, due to the injection aseptic apyrogeneity of requirement, production process is strict, Step is more to need appointed condition higher, and in injection medicine generally with molecular state micron The solid small particles of level are dispersed in water, and decentralization is very big, and often to produce medicine by high-temperature sterilization Thing hydrolysis, oxidation, solids coalescence become big equistability problem.Simultaneously because injection is directly fast Speed enters human body, the protection without human body normal physiological barrier, if therefore dosage it is improper or inject it is too fast, Or drug quality has problem, it is possible to bring harm to patient, or even after causing to retrieve Really.In addition injection pain, can not by patient's self-administer, injection site produce scleroma and vein note Penetrate the problem existed when causing vascular inflammation to be all clinical practice.
CN101732251A discloses a kind of oxiracetam liposome, solid by Oxiracetam, phosphatide, courage Alcohol, Tween 80 and appropriate osmotic pressure regulator and cushioning liquid are obtained；The liposome stability is good, Envelop rate is high, toxic and side effect is small；But liposome preparation complex process, is not suitable for large-scale production； Curative effect of the what is more important liposome in human body need further research, and the current country rarely has fat Liposome preparation is used for clinic.
CN103494790A discloses a kind of oxiracetam capsule, by xylitol, lubricant and crystalline The Oxiracetam of formula is obtained；Obtained oxiracetam capsule quality stability is significantly improved, preparation technology Simply, production cost reduction.CN104739796A discloses a kind of Oxiracetam tablet, by a certain amount of Oxiracetam, filler, disintegrant, binder and lubricant be 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, Drug-eluting is conducive to absorb；It is convenient to take, it is oral after the dispersion that can add water, can be also contained in mouth and be suck Take or swallow.Oral dispersable tablet equally exists the problem choked and cough, and suckes and take dispersible tablet, and it works very 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 Oxiracetam, excipient, antiplastering aid and pH adjusting agent are obtained.Freeze-dried powder needs large scale equipment, Produced under very 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
In order to overcome the shortcoming of prior art, according to the first aspect of the invention, the present invention provides a kind of Levo-oxiracetam pelliculae pro cavo oris, the film is that can dissolve with a small amount of saliva in oral cavity, is not required to use water Medication by taking, medication is convenient；And be difficult to spue after being adhered on tongue, suitable child takes.
Unless otherwise specified, number of the present invention is weight portion.
The object of the present invention is achieved like this：
A kind of levo-oxiracetam pelliculae pro cavo oris, by 1-20 parts of levo-oxiracetam, 35-70 parts Filmogen, 5-30 part of filler, 5-25 parts of plasticizer, 1-3 parts of sweetener and 1-5 parts of saliva Stimulant is obtained；The filmogen is comprising maltodextrin and at least another macromolecule filming material； Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, general The blue polysaccharide in Shandong, PVP-vinyl acetate or sodium carboxymethylcellulose；The plasticizer is selected from glycerine, third Glycol, glyceryl triacetate, triethyl citrate, dibutyl phthalate, PEG400 and PEG600 In one or more combination；The filler be selected from microcrystalline cellulose, low-substituted hydroxypropyl cellulose, One or more combination in pregelatinized starch, Ac-Di-Sol；The sweetener is peace One or more mixing in match honey, sweet Abbas, Sucralose, essence, saccharin；The saliva Stimulant is selected from the one or more combination in citric acid, malic acid, lactic acid, ascorbic acid.
Inventor has found that the levo-oxiracetam film quality of preparation is unstable in R＆D process, holds The problems such as easily occurring that matter is soft, filming performance is poor, be difficult to the demoulding.
An embodiment of the invention,
Above-mentioned levo-oxiracetam pelliculae pro cavo oris, by 4-18 parts of levo-oxiracetam, 40-70 parts Filmogen, 10-30 part of filler, 10-25 parts of plasticizer, 1-3 parts of sweetener and 1-5 parts Saliva stimulant is obtained；The filmogen is comprising maltodextrin and at least another macromolecule filming Material；Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, alginic acid Sodium, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose, wherein hydroxypropyl cellulose, Amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose Consumption is respectively：5 parts~40 parts, 10~15 parts, 3~15 parts, 4~12 parts, 12~18 parts, 5~ 18 parts.
An embodiment of the invention,
A kind of levo-oxiracetam pelliculae pro cavo oris, by 5-18 parts of levo-oxiracetam, 40-65 parts Filmogen, 10-20 part of filler, 15-25 parts of plasticizer, 1-3 parts of sweetener and 2-4 parts of saliva Liquid stimulant is obtained；The filmogen is that maltodextrin and hydroxypropyl methyl cellulose are combined, Wherein HPMC consumption is 18 parts~30 parts；The filler is microcrystalline cellulose or low takes For hydroxypropyl cellulose；The plasticizer is the one kind in propane diols, glycerine or triethyl citrate； The sweetener is Sucralose or Aspartame；The saliva stimulant be citric acid, malic acid or One kind in ascorbic acid.
An embodiment of the invention,
A kind of levo-oxiracetam pelliculae pro cavo oris, by 3-15 parts of levo-oxiracetam, 35-65 parts Filmogen, 10-20 part of filler, 10-25 parts of plasticizer, 1-3 parts of flavouring and 2-5 parts of saliva Liquid stimulant is obtained；The filmogen is that maltodextrin and sodium alginate are constituted, wherein sodium alginate Consumption is 8 parts~12 parts；The filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；Institute Plasticizer is stated for glycerine or glyceryl triacetate；The sweetener is acesulfame potassium or Sucralose；It is described Saliva stimulant is citric acid or lactic acid.
An embodiment of the invention,
A kind of levo-oxiracetam pelliculae pro cavo oris, by 8-20 parts of levo-oxiracetam, 55-70 parts Filmogen, 10-25 part of filler, 8-20 parts of plasticizer, 1-3 parts of flavouring and 2-3 parts of saliva Liquid stimulant is obtained；The filmogen is that maltodextrin and pulullan polysaccharide are constituted, wherein Propiram Polysaccharide consumption is 5 parts~15 parts；The filler is low-substituted hydroxypropyl cellulose or cross-linked carboxymethyl Sodium cellulosate；The plasticizer is propane diols or glyceryl triacetate；The sweetener be essence or Ah Bath is sweet；The saliva stimulant is citric acid or malic acid.
An embodiment of the invention,
A kind of levo-oxiracetam pelliculae pro cavo oris, by the levo-oxiracetam including 5-15 parts, 45-60 Part filmogen, 10-20 parts of filler, 10-25 parts of plasticizer, 1-3 parts of flavouring and 2-4 Part saliva stimulant is obtained；The filmogen is maltodextrin, hydroxypropyl methyl cellulose and side chain Starch constitute, wherein HPMC consumption be 10 parts~20 parts, amylopectin consumption be 12~ 15 parts；The filler is microcrystalline cellulose or Ac-Di-Sol；The plasticizer is sweet Oil or triethyl citrate；The sweetener is essence or Sucralose；The saliva stimulant is breast Acid or malic acid.
An embodiment of the invention,
A kind of levo-oxiracetam pelliculae pro cavo oris, by 6-15 parts of levo-oxiracetam, 45-65 parts Filmogen, 12-20 part of filler, 15-25 parts of plasticizer, 1-3 parts of flavouring and 2-3 parts of saliva Liquid stimulant is obtained；The filmogen is maltodextrin, pulullan polysaccharide and PVP-vinyl acetate Composition, wherein pulullan polysaccharide consumption be 7 parts~10 parts, PVP-vinyl acetate consumption be 15~ 18 parts；The filler is microcrystalline cellulose or pregelatinized starch；The plasticizer is phthalic acid Dibutyl ester or glyceryl triacetate；The sweetener is for Abbas is sweet or saccharin；The saliva stimulant It is lactic acid or ascorbic acid.
An embodiment of the invention,
A kind of levo-oxiracetam orodispersible film, by 5-20 parts of levo-oxiracetam, 55-70 Part filmogen, 5-20 parts of filler, 10-20 parts of plasticizer, 1-2 parts of sweetener and 3-5 Part saliva stimulant is obtained；The filmogen is maltodextrin, sodium alginate and pulullan polysaccharide group Into wherein sodium alginate consumption is 12 parts~15 parts, and pulullan polysaccharide consumption is 6 parts~9 parts；Institute Filler is stated for pregelatinized starch or Ac-Di-Sol；The plasticizer is propane diols or neighbour Dibatyl phithalate；The sweetener is saccharin or Sucralose；The saliva stimulant is lemon Acid or lactic acid.
According to the second aspect of the invention, the present invention provides the system of above-mentioned levo-oxiracetam pelliculae pro cavo oris Preparation Method, the method step is simple, is adapted to industrialized production.
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by filmogen deionized water dissolving, slough bubble and uniform viscous fluid is obtained；
2) plasticizer, filler, saliva stimulant, sweetener deionized water are uniformly dispersed into point Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add left-handed Aura It is western smooth, it is uniformly dispersed, then stand and slough bubble；
4) the viscous fluid medicine film coating dryer coating after bubble, dry, stripping will be removed to obtain final product.
Above-mentioned steps 1), step 2) in deionized water consumption it is common by this area according to actual conditions Technical staff determines.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 35-70 parts of filmogen deionized water dissolving, bubble is sloughed prepared uniform sticky Liquid；
2) it is 5-25 parts of plasticizer, 5-30 parts of filler, 1-5 parts of saliva stimulant and 1-3 parts is sweet Taste agent deionized water is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 1-20 parts Levo-oxiracetam, is uniformly dispersed, and then stands and sloughs bubble；
4) the viscous fluid medicine film coating dryer coating after bubble, dry, stripping will be removed to obtain final product.
In order to strengthen patient adaptability, and disintegration time limited of the invention is rationally controlled, left-handed Austria of the invention The thickness of La Xitan orodispersible films is 80~120 μm.
In order to further improve the quality of levo-oxiracetam orodispersible film of the present invention, above-mentioned medicine film The coating speed of drying machine is 50-90cm/min, and drying temperature is 65-85 DEG C.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 40-65 parts of filmogen (maltodextrin and hydroxypropyl methyl cellulose are combined, its Middle HPMC consumption is 18 parts~30 parts) deionized water dissolving is used, slough bubble and be obtained Even viscous fluid；
2) by 15-25 parts of plasticizer (propane diols, glycerine or triethyl citrate), 10-20 parts Filler (microcrystalline cellulose or low-substituted hydroxypropyl cellulose), 2-4 parts of saliva stimulant (citric acid, Malic acid or ascorbic acid) and 1-3 parts of sweetener (Sucralose or Aspartame) use deionized water It is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 5-18 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 55-85cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 35-65 parts of filmogen, (maltodextrin and sodium alginate are combined, wherein alginic acid Sodium consumption is 8 parts~12 parts) deionized water dissolving is used, slough bubble and uniform viscous fluid is obtained；
2) it is 10-25 parts of plasticizer (glycerine or glyceryl triacetate), 10-20 parts of filler is (low Substitution hydroxypropyl cellulose or pregelatinized starch), 2-4 parts of saliva stimulant (citric acid or lactic acid) and 1-3 parts of sweetener (acesulfame potassium or Sucralose) is uniformly dispersed into dispersion liquid with deionized water；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 3-15 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-75cm/min, then with 70-82 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 55-70 parts of filmogen, (maltodextrin and pulullan polysaccharide are combined, wherein general Shandong Blue polysaccharide consumption is 5 parts~15 parts) deionized water dissolving is used, slough bubble and uniform viscous fluid is obtained；
2) by 8-20 parts of plasticizer (propane diols or glyceryl triacetate), 10-25 parts of filler (low-substituted hydroxypropyl cellulose or Ac-Di-Sol), 2-3 parts of saliva stimulant (lemon Acid or malic acid) and 1-3 parts of sweetener (essence or Abbas are sweet) be uniformly dispersed into deionized water Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-20 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 65-78cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam orodispersible film, using following steps：
1) by 45-60 parts of filmogen (maltodextrin, hydroxypropyl methyl cellulose and amylopectin group Conjunction is formed, wherein HPMC consumption be 10 parts~20 parts, amylopectin consumption be 12~ 15 parts) deionized water dissolving is used, slough bubble and uniform viscous fluid is obtained；
2) it is 10-25 parts of plasticizer (glycerine or triethyl citrate), 10-20 parts of filler is (micro- Crystalline cellulose or Ac-Di-Sol), 2-4 parts of saliva stimulant (lactic acid or malic acid) and 1-3 parts of sweetener (essence or Sucralose) is uniformly dispersed into dispersion liquid with deionized water；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 5-15 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-75cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam orodispersible film, using following steps：
1) by 45-65 parts of filmogen (maltodextrin, pulullan polysaccharide and PVP-vinyl acetate Combine, wherein pulullan polysaccharide consumption is 7 parts~10 parts, PVP-vinyl acetate consumption is 15~18 parts) deionized water dissolving is used, slough bubble and uniform viscous fluid is obtained；
2) by 15-25 parts of plasticizer (dibutyl phthalate or glyceryl triacetate), 12-20 Part filler (microcrystalline cellulose or pregelatinized starch), 2-3 parts of saliva stimulant (ascorbic acid or Lactic acid) and 1-3 parts of sweetener (Abbas sweet or saccharin) be uniformly dispersed into dispersion liquid with deionized water；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 6-15 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-75cm/min, then with 70-80 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of levo-oxiracetam orodispersible film, using following steps：
1) by 55-70 parts of filmogen (maltodextrin, sodium alginate and pulullan polysaccharide are combined, Wherein sodium alginate consumption be 12 parts~15 parts, pulullan polysaccharide consumption be 6 parts~9 parts) spend from Sub- water dissolves, slough bubble and uniform viscous fluid are obtained；
2) 10-20 parts of plasticizer (propane diols or dibutyl phthalate), 5-20 parts are filled out Fill agent (pregelatinized starch or Ac-Di-Sol), 3-5 parts of saliva stimulant (citric acid or Lactic acid) and 1-2 parts of sweetener (saccharin or Sucralose) be uniformly dispersed into dispersion liquid with deionized water；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 5-20 parts Levo-oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 50-80cm/min, then with 65-85 DEG C of drying, stripping is obtained final product.
The invention has the advantages that：
Levo-oxiracetam pelliculae pro cavo oris prepared by the present invention, it is solvable with a small amount of saliva in oral cavity Solution, medication by being not required to water delivery service, medication is convenient；And be difficult to spue after being adhered on tongue, it is adapted to The patient of dysphagia, and by mucosal absorption, it is to avoid first to cross elimination effect, improves biology Availability, reduces pharmaceutical dosage, so as to reduce drug side-effect.Present invention selection specified quantitative Levo-oxiracetam, filmogen, filler and plasticizer are combined, and selection malt paste meticulously Smart and at least another macromolecular material (hydroxypropyl cellulose, amylopectin, sodium alginate, Pu Lu Blue polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose) compound film material is formed, so as to solve Levo-oxiracetam pelliculae pro cavo oris easily occurs that matter is soft, filming performance is poor, be difficult to the technical problems such as the demoulding, So as to improve product quality.The present invention passes through the group of specific compound film material, plasticizer and filler Close, so as to the levo-oxiracetam pelliculae pro cavo oris mechanical performance for solving preparation is bad, disintegration time is long, Film has fragility, the technical problem such as is easily broken off, so as to ensure that product quality.The present invention uses medicine Film film applicator prepares levo-oxiracetam pelliculae pro cavo oris, and strictly controls thickness, the coating speed of film And drying temperature, so as to stabilize technique, it is ensured that the quality of product so that fragility of the invention, The aspect such as disintegration time limited and solution time is more conducive to clinical practice；And preparation method of the present invention is simple, Large industry equipment is not needed, is adapted to industrialized 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 levo-oxiracetam raw material (content 99.8%, Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. provides, and lot number is：20150208)；Hydroxypropyl Methylcellulose (HPMC, Dow Chemical company, specification E50)；Hydroxypropylcellulose (HPC, the U.S. Ashland companies, specification LF)；Sodium alginate (Shandong Fu Ruida bio tech ltd)；It is poly- Ethylene glycol (PEG) 400 (Hunan Hua pharmaceutical Co. Ltds)；(Hunan that health pharmacy share has glycerine Limit company)；Triethyl citrate (TEC, Bangbu Fengyuan Medicine Sci-Tech Development Co., Ltd)；Low substitution Hydroxypropyl cellulose (L-HPC), pregelatinized starch (Anhui Shanhe Medicinal Subsidiary Material Co., Ltd.)； Microcrystalline cellulose (MCC, German JRS companies, specification VIVAPUR 101)；Acetonitrile, methyl alcohol are chromatogram Pure, other reagents are pure for analysis.
Medicine film coating dryer used of the invention is commercially available prod, it is also possible to reference to CN 201668734U Self-control, medicine film coating dryer by main box, auxiliary box body, peristaltic pump, flat scraper, master roller, Deputy roller cylinder, conveyer belt, heating electroplax, induced-draught fan and rolling-up mechanism composition.Its action principle is medicine Slurries are added on a moving belt by peristaltic pump, and conveyer belt is operated under the drive of motor around main box, Liquid on conveyer belt is hung into film, the air heating of heating electroplax by flat scraper, and induced-draught fan will be main Air in casing is taken away, air is flowed in main box, and the solvent of liquid is flung to, and is dried to Type, rolling-up mechanism collects the medicine film of shaping.
Embodiment 1
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 65g filmogens, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxypropyl cellulose Consumption is 30g) 80mL deionized water dissolvings are used, slough bubble and uniform viscous fluid is obtained；
2) by 25g glycerine, 15g microcrystalline celluloses, 4g citric acids and 2g Sucraloses 50mL Deionized water is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 18g left-handed Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60cm/min, then with 75-77 DEG C of drying, stripping is obtained final product.
Embodiment 2
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 40g, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxy propyl cellulose Plain consumption is 18g) 50mL deionized water dissolvings are used, slough bubble and uniform viscous fluid is obtained；
2) by 15g propane diols, 10g low-substituted hydroxypropyl celluloses, 2g malic acid and 2g acesulfame potassiums Dispersion liquid is uniformly dispersed into 60mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 18g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 85cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 3
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxy propyl cellulose Plain consumption is 25g) 50mL deionized water dissolvings are used, slough bubble and uniform viscous fluid is obtained；
2) by 15g triethyl citrates, 19g microcrystalline cellulose 3g malic acid and the sweet use of 1g Abbas 40mL deionized waters are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 15g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 4
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 65g, (maltodextrin and amylopectin are constituted, and wherein amylopectin consumption is 80mL deionized water dissolvings 12g) are used, bubble is sloughed and uniform viscous fluid is obtained；
2) by 25g propane diols, 15g low-substituted hydroxypropyl celluloses, 4g lactic acid and 3g Sucraloses Dispersion liquid is uniformly dispersed into 30mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10g left-handed Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 65cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 5
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 45g, (maltodextrin and amylopectin are constituted, and wherein amylopectin consumption is Deionized water dissolving 8g) is used, bubble is sloughed and uniform viscous fluid is obtained；
2) by 10g dibutyl phthalates, 20g pregelatinized starch, 2g citric acids and 1g saccharin Dispersion liquid is uniformly dispersed into 60mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 18g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 6
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g, (maltodextrin and amylopectin are constituted, and wherein amylopectin consumption is 55mL deionized water dissolvings 10g) are used, bubble is sloughed and uniform viscous fluid is obtained；
2) 18g dibutyl phthalates, 17g pregelatinized starch, 3g citric acids and 2g are pacified and is matched Honey is uniformly dispersed into dispersion liquid with 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 12g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 74cm/min, then with 80-82 DEG C of drying, stripping is obtained final product.
Embodiment 7
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 70g, (maltodextrin and sodium alginate are constituted, and wherein sodium alginate consumption is 80mL deionized water dissolvings 15g) are used, bubble is sloughed and uniform viscous fluid is obtained；
2) it is 20g glycerine, 25g low-substituted hydroxypropyl celluloses, 3g malic acid and 2g Abbas is sweet Dispersion liquid is uniformly dispersed into 30mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 20g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 65cm/min, then with 76-78 DEG C of drying, stripping is obtained final product.
Embodiment 8
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g, (maltodextrin and sodium alginate are constituted, and wherein sodium alginate consumption is 65mL deionized water dissolvings 8g) are used, bubble is sloughed and uniform viscous fluid is obtained；
2) by 16g dibutyl phthalates, 15g Ac-Di-Sols, 3g citric acids With 1g essence dispersion liquid is uniformly dispersed into 50mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 12g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 9
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 60g, (maltodextrin and sodium alginate are constituted, and wherein sodium alginate consumption is 65mL deionized water dissolvings 12g) are used, bubble is sloughed and uniform viscous fluid is obtained；
2) by 10g glycerine, 15g low-substituted hydroxypropyl celluloses, 2g essence and the sweet use of 3g Abbas 35mL deionized waters are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 12g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 78cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 10
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g (maltodextrin, hydroxypropyl cellulose and amylopectin composition, wherein Hydroxypropyl cellulose consumption is 15g, and amylopectin consumption is 15g) 50mL deionized water dissolvings are used, take off Degassing is brewed to obtain uniform viscous fluid；
2) by 15g glycerine, 20g microcrystalline celluloses, 3g malic acid and 2g acesulfame potassiums 50mL go from Sub- moisture dissipates non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 14g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60cm/min, then with 80-82 DEG C of drying, stripping is obtained final product.
Embodiment 11
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g (maltodextrin, hydroxypropyl cellulose and amylopectin composition, wherein Hydroxypropyl cellulose consumption is 20g, and amylopectin consumption is 12g) 80mL deionized water dissolvings are used, take off Degassing is brewed to obtain uniform viscous fluid；
2) by 16g triethyl citrates, 20g Ac-Di-Sols, 2g lactic acid and 2g Ahs The sweet 50mL deionized waters of Bath are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 10g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 75cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 12
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 60g (maltodextrin, hydroxypropyl cellulose and amylopectin composition, wherein Hydroxypropyl cellulose consumption is 10g, and amylopectin consumption is 12g) 65mL deionized water dissolvings are used, take off Degassing is brewed to obtain uniform viscous fluid；
2) 15g glycerine, 15g microcrystalline celluloses, 3g malic acid and 2g Sucraloses are gone with 40mL Ionized water is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add the left-handed Austria of 8g La Xitan is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 13
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 45g (maltodextrin, pulullan polysaccharide and PVP-vinyl acetate composition, Wherein pulullan polysaccharide consumption is 7g, and PVP-vinyl acetate consumption is 15g) use 50mL deionized waters Dissolving, sloughs bubble and uniform viscous fluid is obtained；
2) 15g glyceryl triacetates, 25g microcrystalline celluloses, 3g ascorbic acid and 1g saccharin are used 50mL deionized waters are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 10g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 72cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 14
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 63g (maltodextrin, pulullan polysaccharide and PVP-vinyl acetate composition, Wherein pulullan polysaccharide consumption is 10g, and PVP-vinyl acetate consumption is 18g) use 70mL deionizations Water dissolves, slough bubble and uniform viscous fluid are obtained；
2) 25g dibutyl phthalates, 15g pregelatinized starch, 3g lactic acid are used and 2g Ah bars This sweet 30mL deionized water is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 15g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 85-88 DEG C of drying, stripping is obtained final product.
Embodiment 15
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g (maltodextrin, pulullan polysaccharide and PVP-vinyl acetate composition, Wherein pulullan polysaccharide consumption is 8g, and PVP-vinyl acetate consumption is 16g) use 50mL deionized waters Dissolving, sloughs bubble and uniform viscous fluid is obtained；
2) by 16g glyceryl triacetates, 21g pregelatinized starch, 2g ascorbic acid and 1g Abbas Sweet 50mL deionized waters are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add that 8g's is left-handed Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 78-80 DEG C of drying, stripping is obtained final product.
Embodiment 16
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by filmogen (maltodextrin, pulullan polysaccharide and the sodium alginate composition, wherein general of 55g Shandong orchid polysaccharide consumption is 7g, and sodium alginate consumption is 13g) 50mL deionized water dissolvings are used, slough gas It is brewed to obtain uniform viscous fluid；
2) 15g propane diols, 20g Ac-Di-Sols, 5g citric acids and 1g saccharin are used 30mL deionized waters are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 15g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 65cm/min, then with 75-77 DEG C of drying, stripping is obtained final product.
Embodiment 17
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by filmogen (maltodextrin, pulullan polysaccharide and the sodium alginate composition, wherein general of 60g Shandong orchid polysaccharide consumption is 9g, and sodium alginate consumption is 15g) 70mL deionized water dissolvings are used, slough gas It is brewed to obtain uniform viscous fluid；
2) 20g propane diols, 17g pregelatinized starch, 4g lactic acid and 2g Sucraloses are gone with 30mL Ionized water is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 10g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 80cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 18
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by filmogen (maltodextrin, pulullan polysaccharide and the sodium alginate composition, wherein general of 50g Shandong orchid polysaccharide consumption is 6g, and sodium alginate consumption is 12g) 55mL deionized water dissolvings are used, slough gas It is brewed to obtain uniform viscous fluid；
2) by 15g lead dibatyl phithalate, 20g Ac-Di-Sols, 3g citric acids and 2g Sucraloses are uniformly dispersed into dispersion liquid with 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 13g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 19
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the maltodextrin of 50g 55mL deionized water dissolvings, slough bubble and uniform gluing is obtained Magma；
2) by 15g lead dibatyl phithalate, 20g Ac-Di-Sols, 3g citric acids and 2g Sucraloses are uniformly dispersed into dispersion liquid with 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 13g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 20
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g (hydroxypropyl cellulose, pulullan polysaccharide and sodium alginate composition, its Middle hydroxypropyl cellulose 32g, amylopectin consumption is 6g, and sodium alginate consumption is 12g) use 55mL Deionized water dissolving, sloughs bubble and uniform viscous fluid is obtained；
2) by 15g lead dibatyl phithalate, 20g Ac-Di-Sols, 3g citric acids and 2g Sucraloses are uniformly dispersed into dispersion liquid with 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 13g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 21
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by filmogen (maltodextrin, pulullan polysaccharide and the sodium alginate composition, wherein general of 50g Shandong orchid polysaccharide consumption is 6g, and sodium alginate consumption is 12g) 55mL deionized water dissolvings are used, slough gas It is brewed to obtain uniform viscous fluid；
2) by 15g dioctyl phthalates, 20g Ac-Di-Sols, 3g citric acids and 2g Sucraloses are uniformly dispersed into dispersion liquid with 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 13g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 20cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 22
The preparation of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by the filmogen of 50g (hydroxypropyl cellulose, pulullan polysaccharide and sodium alginate composition, its Middle hydroxypropyl cellulose 32g, pulullan polysaccharide consumption is 6g, and sodium alginate consumption is 12g) use 55mL Deionized water dissolving, sloughs bubble and uniform viscous fluid is obtained；
2) by 15g glycerine, 20g Ac-Di-Sols, 3g citric acids and 2g Sucraloses Dispersion liquid is uniformly dispersed into 45mL deionized waters；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add a left side of 13g Rotation Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 70cm/min, then with 50 DEG C of dryings, stripping is obtained final product.
Embodiment 23
Levo-oxiracetam pelliculae pro cavo oris obtained in embodiment 1-22 is evaluated, including outward appearance, thickness Degree, ifs vitro disintegration, the evaluation of mechanical properties.
Evaluation method
Ocular estimate：Whether observation membrane surface is complete bright and clean, and whether thickness is consistent, and whether color and luster is equal It is even, whether there is obvious bubble.
Thickness measurement：Use resolution ratio carries out thickness survey for the digimatic micrometer of 0.001mm to film Amount, determines 3 times respectively in every piece of the 3 of film different parts, and record data obtains average thickness.
Ifs vitro disintegration time study：The disintegrating property of film and molten is investigated by the disintegration time for determining film Solution ability.It is placed on magnetic stirring apparatus in the beaker that 50mL distilled water is added 100mL, 37 DEG C of perseverances Be clipped in test film on clip to be put into water-bath start timing by tepidarium, rotating speed 100r/min, records The time of film dissolving.In this experiment, every piece of equal block size of random cropping 3 of film is 1 × 1cm2 Membranelle determine, using three average values of measurement result as measurement result.
Mechanical performance is evaluated：
This experiment has used the universal testing machine of model 3365 to comment the mechanical performance of film Valency.It is 2 × 0.5cm by size2Film be put between two clips at a distance of 5cm.Draw vice with The speed membrane of 10mm/min.The elastic modelling quantity (EM) of film, refers in elastic deformation stage, outward Plus the ratio of stress and strain power, it is possible to use formula below is calculated：
Elastic modelling quantity=applied stress/adaptability to changes/area of section.
The tensile strength (TS) of film is also strength degree, refers to that material bears maximum stress before breaking It is worth, computing formula is：
Tensile strength=applied stress/cross-sectional area.
The percent elongation (E%) of film is calculated by following formula：
Percent elongation=length incrementss/the original length × 100.
The test result of the levo-oxiracetam pelliculae pro cavo oris of embodiment 1-8 is as follows：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display above, the levo-oxiracetam pelliculae pro cavo oris surface prepared by embodiment 1-8 is smooth, Thickness evenness preferably, possesses suitable suppleness and tensile property, and conveniently stripped, disintegration time exists 20s or so.
The levo-oxiracetam pelliculae pro cavo oris the performance test results such as following table of embodiment 9-15：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display above, the levo-oxiracetam pelliculae pro cavo oris surface prepared by embodiment 9-15 is smooth, Thickness evenness preferably, possesses suitable suppleness and tensile property, and conveniently stripped, disintegration time exists 20s or so.
The test result of the levo-oxiracetam pelliculae pro cavo oris of embodiment 16-22 is as follows：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display, the levo-oxiracetam pelliculae pro cavo oris surface light prepared by embodiment 16-18 above Sliding, thickness evenness preferably, possesses suitable suppleness and tensile property, conveniently stripped, during disintegration Between in 20s or so, no more than 24s；The membrane surface of embodiment 19 has projection, and the demoulding is also more stranded Difficulty, and disintegration time limited also relative extension；The surface of embodiment 20 is smooth, and toughness is preferable, also easily The demoulding, but disintegration time is slightly long；The membrane surface of embodiment 21 has projection, and the demoulding is also more difficult, And disintegration time limited also relative extension；The film of embodiment 22 is partially wet, there is adhesion phenomenon, disintegration time It is slightly long.
Levo-oxiracetam pelliculae pro cavo oris obtained in embodiment 1-22 is carried out into dissolution in vitro experiment, is tied Fruit shows：The levo-oxiracetam pelliculae pro cavo oris of embodiment 1-18 starts disintegration, drug release in 10s Rapidly, dissolution is complete more than the basic dissolutions of 90%, 10min in 5min；Obtained in embodiment 19-22 Start disintegration in levo-oxiracetam pelliculae pro cavo oris 10s, drug release is more rapid, dissolution surpasses in 5min Cross dissolution in 70%, 10min complete more than the basic dissolutions of 90%, 20min；
Embodiment 19 and embodiment 20 have investigated filmogen to influence of the invention, alone malt paste , used as filmogen, disintegration time is slightly long, there is the slightly poor situation of film forming, can cause the demoulding for essence Difficult (embodiment 19)；Prepared by without maltodextrin film, filming performance is preferably, easily de- Mould, but disintegration time is (embodiment 20) more long.Embodiment 21 and embodiment 22 have investigated masking During the influence of coating speed and drying temperature to film, wherein coating speed it is too fast can cause it is partially wet, There is adhesion phenomenon；Coating speed can cause film overdrying slowly excessively, so that film is more crisp.Drying temperature The brittleness and humidity of film can equally be influenceed.
To sum up, levo-oxiracetam pelliculae pro cavo oris appearance uniform of the present invention is complete, uniform color, thickness Unanimously, physics and stable chemical nature, disintegration time are short, and dissolution rate is fast, work rapid.

Claims (8)

1. a kind of levo-oxiracetam pelliculae pro cavo oris, is obtained by 1-20 parts of levo-oxiracetam, 35-70 parts of filmogen, 5-30 parts of filler, 5-25 parts of plasticizer, 1-3 parts of sweetener and 1-5 parts of saliva stimulant；The filmogen is comprising maltodextrin and at least another macromolecule filming material；Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose；The plasticizer is selected from the one or more combination in glycerine, propane diols, glyceryl triacetate, triethyl citrate, dibutyl phthalate, PEG400 and PEG600；The filler is selected from the one or more combination in microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, Ac-Di-Sol；The sweetener is one or more mixing in acesulfame potassium, sweet Abbas, Sucralose, essence, saccharin；The saliva stimulant is selected from the one or more combination in citric acid, malic acid, lactic acid, ascorbic acid.
2. levo-oxiracetam pelliculae pro cavo oris as claimed in claim 1, it is characterised in that：It is obtained by 4-18 parts of levo-oxiracetam, 40-70 parts of filmogen, 10-30 parts of filler, 10-25 parts of plasticizer, 1-3 parts of sweetener and 1-5 parts of saliva stimulant；The filmogen is comprising maltodextrin and at least another macromolecule filming material；Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose, and the consumption of wherein hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose is respectively：5 parts~40 parts, 10~15 parts, 3~15 parts, 4~12 parts, 12~18 parts, 5~18 parts.
3. levo-oxiracetam pelliculae pro cavo oris as claimed in claim 1, it is characterised in that：It is obtained by 3-15 parts of levo-oxiracetam, 35-65 parts of filmogen, 10-20 parts of filler, 10-25 parts of plasticizer, 1-3 parts of flavouring and 2-5 parts of saliva stimulant；The filmogen is that maltodextrin and sodium alginate are constituted, and wherein sodium alginate consumption is 8 parts~12 parts；The filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；The plasticizer is glycerine or glyceryl triacetate；The sweetener is acesulfame potassium or Sucralose；The saliva stimulant is citric acid or lactic acid.
4. levo-oxiracetam pelliculae pro cavo oris as claimed in claim 1, it is characterised in that：It is obtained by 5-20 parts of levo-oxiracetam, 55-70 parts of filmogen, 5-20 parts of filler, 10-20 parts of plasticizer, 1-2 parts of sweetener and 3-5 parts of saliva stimulant；The filmogen is maltodextrin, sodium alginate and pulullan polysaccharide composition, and wherein sodium alginate consumption is 12 parts~15 parts, and pulullan polysaccharide consumption is 6 parts~9 parts；The filler is pregelatinized starch or Ac-Di-Sol；The plasticizer is propane diols or dibutyl phthalate；The sweetener is saccharin or Sucralose；The saliva stimulant is citric acid or lactic acid.
5. as described in claim any one of 1-4 levo-oxiracetam pelliculae pro cavo oris preparation method, it is characterised in that use following steps：
1）By 35-70 parts of filmogen deionized water dissolving, slough bubble and uniform viscous fluid is obtained；
2）5-25 parts of plasticizer, 5-30 parts of filler, 1-5 parts of saliva stimulant and 1-3 parts of sweetener deionized water are uniformly dispersed into dispersion liquid；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 1-20 parts of levo-oxiracetam, be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid medicine film coating dryer coating after bubble, dry, stripping will be removed to obtain final product.
6. method as claimed in claim 5, it is characterised in that：The coating speed of the medicine film drying machine is 50-90cm/min, and drying temperature is 65-85 DEG C.
7. a kind of preparation method of levo-oxiracetam pelliculae pro cavo oris, using following steps：
1) by 35-65 parts of filmogen deionized water dissolving, slough bubble and uniform viscous fluid is obtained；The filmogen is that maltodextrin and sodium alginate are combined, and wherein sodium alginate consumption is 8 parts~12 parts；
2）10-25 parts of plasticizer, 10-20 parts of filler, 2-4 parts of saliva stimulant and 1-3 parts of sweetener deionized water are uniformly dispersed into dispersion liquid；The plasticizer is glycerine or glyceryl triacetate；The filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；The saliva stimulant is citric acid or lactic acid；The sweetener is acesulfame potassium or Sucralose；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 3-15 parts of levo-oxiracetam to be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-75cm/min, and then with 70-82 DEG C of drying, stripping is obtained final product.
8. a kind of preparation method of levo-oxiracetam orodispersible film, using following steps：
1) by 55-70 parts of filmogen deionized water dissolving, slough bubble and uniform viscous fluid is obtained；The filmogen is combined for maltodextrin, sodium alginate and pulullan polysaccharide, and wherein sodium alginate consumption is 12 parts~15 parts, and pulullan polysaccharide consumption is 6 parts~9 parts；
2）10-20 parts of plasticizer, 5-20 parts of filler, 3-5 parts of saliva stimulant and 1-2 parts of sweetener deionized water are uniformly dispersed into dispersion liquid；The plasticizer is propane diols or dibutyl phthalate；The filler is pregelatinized starch or Ac-Di-Sol；The saliva stimulant is citric acid or lactic acid；The sweetener is saccharin or Sucralose；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 5-20 parts of levo-oxiracetam to be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 50-80cm/min, and then with 65-85 DEG C of drying, stripping is obtained final product.
CN201510904232.4A 2015-12-07 2015-12-07 A kind of levo-oxiracetam pelliculae pro cavo oris and preparation method thereof Withdrawn CN106822060A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
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

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Application publication date: 20170613