CN109381448A - A kind of razaxaban oral quick-dissolving film preparation and preparation method thereof - Google Patents
A kind of razaxaban oral quick-dissolving film preparation and preparation method thereof Download PDFInfo
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- CN109381448A CN109381448A CN201710659383.7A CN201710659383A CN109381448A CN 109381448 A CN109381448 A CN 109381448A CN 201710659383 A CN201710659383 A CN 201710659383A CN 109381448 A CN109381448 A CN 109381448A
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- razaxaban
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- dissolving film
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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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
Abstract
The present invention relates to a kind of razaxaban oral quick-dissolving film preparation and preparation method thereof, oral quick-dissolving film preparation disclosed in this invention is made of poorly water soluble drugs razaxaban, water soluble polymer and pharmaceutically acceptable additive.Film thickness prepared by the present invention is uniform, good mechanical property, and disintegration dissolution rate is fast, and dissolution reaches 85% or more in 5min in four kinds of different dissolution mediums.The film is convenient to take, without being delivered with water, absorbs rapidly, patient's compliance can be improved.
Description
Technical field
The present invention relates to a kind of razaxaban oral quick-dissolving film preparations and preparation method thereof.
Background technique
Razaxaban is a kind of oral anticoagulant object of Bayer research and development, the prevention for phlebothrombosis and stroke.The medicine
It in September, 2008 in the granted listing in Europe, and is the new oral anti-coagulants of the first approval listing in China.As a kind of choosing
Selecting property Xa factor inhibitor, relative to traditional anticoagulation medicine such as warfarin and heparin, razaxaban administration mode is one day one
It is secondary oral, it is not necessarily to Medication monitor, dosage is fixed, and the compliance of patient is preferable；Curative effect is not inferior to warfarin；And it can significantly drop
Low bleeding episode.
Razaxaban belongs to the drug (low dissolution, Thief zone) of class ii in Biopharmaceutics Classification system (BCS), molten
Xie Du is the obstacle of its In Vitro Dissolution and body absorption, and current research mainly improves dissolution by post-processing raw material micro mist
Degree improves solution rate and degree, reaches good In Vitro Dissolution, to improve drug bioavailability.
The dosage form of razaxaban only has oral tablet on the market at present, and trade name is visitd auspicious appropriate.Current research is also mainly concentrated
In raising tablet bioavilability etc..However conventional tablet is difficult to swallow, particularly with being unable to leave the bed, the elderly and gulp down after operation
Patients with Difficult is swallowed, compliance is poor.Although oral disnitegration tablet, sublingual tablet, dispersible tablet solve the above problem to a certain extent,
But such preparation process thereof is complicated, while in order to accelerate to be disintegrated, joined a large amount of disintegrating agent in the preparation, so that these agent
Type has the shortcomings that be easy to that moisture absorption, friability be big, mouthfeel has sand type, has higher requirements to production, packaging, storage.
Oral quick-dissolving film preparation (Oral films, OFs) combines piece as a kind of novel oral drug delivery system
The dosage of agent is accurate and easy-to-swallow, the rapid-action advantage of liquid preparation, has dissolution rate fast, drug bioavailability is high
The features such as.Drug contacts a small amount of saliva in the oral cavity can be disintegrated in 30 seconds, dissolve out, and take without chewing without water, be
A kind of novel quick drug release preparation.For preparation easy to produce, transport and clinical use, which is required to have preferable mechanical
Performance, i.e. intensity and tensile property etc.；Meanwhile because the thickness of film directly affects its uniformity of dosage units, to guarantee that its content is equal
One property also has higher requirements to the caliper uniformity of the dosage form.It is different by using different technologies, addition during the preparation process
Auxiliary material the products of different purposes, such as instant film, sustained release film formulation can be obtained.Upper common film preparation method is produced at present
There are solvent casting method, hot melt extruded method, solid dispersion extrusion, rolled-on method, semisolid casting method and solvent seasoning method etc..
Oral instant is made in razaxaban from the aspect of improving patient medication compliance according to clinical application demand
Film, without using water when medication, interior fater disintegration in oral cavity, no sand type is especially suitable for being unable to leave the bed after operation, is old and gulp down
Swallow Patients with Difficult；And its simple production process, it is at low cost, it is easy to carry；With high clinical development and use value.As
One new research hotspot, America and Europe have listed the drug of pelliculae pro cavo oris first, and also there is the drug film of about 7 kinds in Japan so far
List marketing, China do not have the listing of oral quick-dissolving film preparation drug at present, this purpose carries out the blank that can fill up this pharmaceutical dosage form,
Increase China's pharmaceuticals industry technical level, pushes Development of pharmaceutical industry.
The quick-release coating material that polyvinyl alcohol mixture is used for damp-proof of our company's novelty, and as preparing film
The filmogen of agent, shows superperformance.The application range of this material has been expanded in research process and gives full play to its conduct
The characteristic property of filmogen finds that the film flat appearance folding resistance of this mixture preparation is good and carries medicine in project research
Amount is big, and the film unit dose area of preparation is small to be easy to transport and carry.
Summary of the invention
Based on this, prepared the present invention provides a kind of razaxaban oral quick-dissolving film preparation and preparation method thereof, the invention
Film thickness is uniform, good mechanical property, and disintegration dissolution rate is fast, in four kinds of different dissolution mediums in 5min dissolution reach 85% with
On.The film is convenient to take, takes without water, can be improved be unable to leave the bed after operation, old and dysphagia patients medication it is suitable
Ying Xing.
The present invention uses and scheme is implemented as follows:
Razaxaban oral quick-dissolving film preparation of the invention is by razaxaban, water soluble polymer and pharmaceutically acceptable
Additive composition.
Razaxaban oral quick-dissolving film preparation of the invention, razaxaban weight are the 1-40% of film weight, water-soluble high score
Sub- polymer weight is the 20-90% of film weight.
Razaxaban oral quick-dissolving film preparation of the invention, the weight ratio of razaxaban, preferably 3-30%, water soluble polymer
The weight ratio of polymer, preferably 40-80%.
Razaxaban oral quick-dissolving film preparation of the invention, the water soluble polymer are selected from polyvinyl alcohol, gather
Vinyl alcohol ethylene glycol copolymer and polyvinyl alcohol mixture, polyvinyl alcohol polyethylene glycol copolymer.
Razaxaban oral quick-dissolving film preparation of the invention, the pharmaceutically acceptable additive include filler 0-
40%(w/w), plasticizer 0-20%(w/w)；Further, may include corrigent 0-10%(w/w), pigment 0-5%(w/w).
Razaxaban oral instant membrane of the invention, the weight percent of the pharmaceutically acceptable additive, is filled out
Fill the preferred 10-30% of agent, the preferred 5-15% of plasticizer, the preferred 0.5-3% of corrigent, the preferred 0.01-3% of pigment.
Razaxaban oral quick-dissolving film preparation of the invention, the filler are selected from starch, pregelatinized starch, lactose, low
Replace the one or more of hydroxypropylcellulose, preferred starch.
Razaxaban oral quick-dissolving film preparation of the invention, the plasticizer are selected from glycerol, polyethylene glycol, propylene glycol, neighbour
The one or more of phthalic acid ester, triethyl citrate, glyceryl triacetate, median chain triglyceride oil, castor oil, it is preferably sweet
Oil.
Razaxaban oral quick-dissolving film preparation of the invention, the corrigent be selected from sucrose, Sucralose, aspartame,
The one or more of acesulfame potassium, Mint Essence, cherry essence, fragrant citrus essence, citric acid, preferably Sucralose.
Razaxaban oral quick-dissolving film preparation of the invention, the pigment are selected from sunset yellow, famille rose, iron oxide.
Further, the razaxaban need to pass through micronization processes, partial size D90≤ 15 μm, preferably D90≤10μm。
It further include defoaming agent and thickener in above-mentioned implementation and preferred embodiment.The defoaming agent is selected from two
Methyl silicon 0-0.5%, thickener are polyvinyl pyrrolidone 0-10%, are the percentage of film weight.
The present invention also provides a kind of methods for preparing razaxaban oral quick-dissolving film preparation, method includes the following steps:
(1) River Bank Stability: water soluble polymer is added to the water by a., and stirring is to being dissolved into clear solution；B. by medicine
Object and additive are added in step (a) acquired solution, are dispersed with stirring uniformly and remove bubble, and uniform drug slurries are made；
(2) it is coated with drying: drug slurry being uniformly coated on back lining materials, 60-90 DEG C dries to obtain film；
(3) cutting packaging: film is cut into unit dose and is packed after being taken off from back lining materials.
In the above preparation method, the water soluble polymer is selected from polyvinyl alcohol, the poly- second two of polyvinyl alcohol
Alcohol copolymer and polyvinyl alcohol mixture, polyvinyl alcohol polyethylene glycol copolymer.
In above-mentioned preparation method, the drug slurry is the evenly dispersed suspension of water-insoluble drug razaxaban
Solution, using continuously stir, one kind of timing occasional agitation, to guarantee uniformity.
In above-mentioned preparation method, the additive include filler, plasticizer, corrigent, pigment one kind or
Person is several, further may include defoaming agent and thickener.
In above-mentioned preparation method, the removing bubble methods include the one kind stand, vacuumize, being added defoaming agent
Or several, preferred vacuum pumping method.
In above-mentioned preparation method, the back lining materials are that polyester (PET) film can be made with a thickness of 150 ~ 220 μm
For razaxaban oral instant membrane with a thickness of 60-120 μm.
Compared with prior art, the invention has the following beneficial effects:
(1) razaxaban oral quick-dissolving film preparation prepared by the present invention, flat appearance, thickness is uniform, and continuous coating thickness difference≤
±5μm；
(2) razaxaban oral quick-dissolving film preparation prepared by the present invention has good tensile property, and shells between back lining materials
It is smaller from intensity, it ensure that integrality of the film in production, transport and storing process, reduce production and transportation and in the process may
Generate the risk of quality problems.
(3) in the preparation method of razaxaban oral quick-dissolving film preparation of the present invention, first water soluble polymer is dissolved complete
After add razaxaban and additive, this with liquid mode can reduce water soluble polymer prepare slurry processes in generate
" flake bubble ", while increase match liquid efficiency, shorten liquid preparation time.
(4) razaxaban oral quick-dissolving film preparation of the present invention and preparation method thereof provides other poorly water soluble drugs and prepares film
Method, have expansibility.
(5) present invention can preferably realize that industrialized production, product quality stable homogeneous are easier to using conventional process equipment
Obtain the assurable product of quality.
Detailed description of the invention
The cumulative defaultlogic (medium: water) of Fig. 1 embodiment 3 and comparative example 3 at each time point；
The cumulative defaultlogic (medium: pH=1.0) of Fig. 2 embodiment 3 and comparative example 3 at each time point；
The cumulative defaultlogic (medium: pH=4.5) of Fig. 3 embodiment 3 and comparative example 3 at each time point；
The cumulative defaultlogic (medium: pH=6.8) of Fig. 4 embodiment 3 and comparative example 3 at each time point；
1 preparation method of Fig. 5 embodiment diagram.
Specific embodiment
Above content of the invention is described in further detail below by way of specific embodiment.But this should not be understood
Range for the above-mentioned theme of the present invention is limited only to example below.Without departing from the idea case in the present invention described above,
The various replacements or change made according to ordinary skill knowledge and customary means, should all be included in the scope of the present invention
It is interior.
Embodiment 1
Prescription:
Preparation method is as shown in Figure 5:
(1) River Bank Stability: weighing 80.0g polyvinyl alcohol polyethylene glycol copolymer and polyvinyl alcohol mixture is added to 400mL water
In, solution is obtained to dissolving within stirring 2 hours；Weigh razaxaban 10.0g, glycerol 15.0g, polyvinylpyrrolidone-K90
6.7g, Sucralose 0.5g and famille rose 0.1g are added in above-mentioned solution, and stirring stands 12h bubble removing, are prepared into uniformly
Razaxaban suspension slurries.
(2) be coated with drying: installation back lining materials polyester film is opened the continuous coating machine of MBCD1.3 type (German OPTIMAGS), setting
Drying temperature is 90 ± 5 DEG C, and adjusting coating thickness makes the film after drying be about 70 μm.
(3) cutting packaging: gained film is cut with 10mg/ piece specification, and is taken off from polyester film, is packed using compound membrane bag.
Embodiment 2
Prescription:
Preparation method:
(1) River Bank Stability: weighing 100.0g polyvinyl alcohol polyethylene glycol copolymer and polyvinyl alcohol mixture is added to 400mL water
In, solution is obtained to dissolving within stirring 2 hours；Weigh razaxaban 50.0g, polyvinylpyrrolidone-K90 6.2g, glycerol
20.0g, Mint Essence 2.0g are added in above-mentioned solution, and stirring stands 12h bubble removing, and it is mixed to be prepared into uniform razaxaban
Suspension slurry.
(2) be coated with drying: installation back lining materials polyester film is opened the continuous coating machine of MBCD1.3 type (German OPTIMAGS), setting
Drying temperature is 85 ± 5 DEG C, and adjusting coating thickness makes the film after drying be about 85 μm.
(3) cutting packaging: gained film is cut with 10mg/ piece specification, and is taken off from polyester film, is packed using compound membrane bag.
Embodiment 3
Prescription:
Preparation method:
(1) River Bank Stability: weighing 135.0g polyvinyl alcohol polyethylene glycol copolymer and polyvinyl alcohol mixture is added to 480mL water
In, stirring obtains solution to dissolving；It weighs razaxaban 25.0g, polyvinylpyrrolidone-K90 10.0g, glycerol 13.0.g, gather
6000 6.7g of ethylene glycol, aspartame 1.1g and dimethicone 0.7g are added in above-mentioned solution, and stirring is evacuated to
0.07-0.09Mpa, pressure maintaining 6-8h bubble removing are prepared into uniform razaxaban suspension slurries.
(2) be coated with drying: installation back lining materials polyester film is opened the continuous coating machine of MBCD1.3 type (German OPTIMAGS), setting
Drying temperature is 85 ± 5 DEG C, and adjusting coating thickness makes the film after drying be about 100 μm.
(3) cutting packaging: gained film is cut with 10mg/ piece specification, and is taken off from polyester film, is packed using compound membrane bag.
Embodiment 4
Prescription:
Preparation process is the same as embodiment 1.
Embodiment 5
Prescription:
Preparation process is the same as embodiment 1.
Embodiment 6
Prescription:
Preparation process is the same as embodiment 1.
The results show that the razaxaban oral quick-dissolving film preparation of embodiment 1-6 preparation, has good planarization, uniform color, without bright
Aobvious bubble.
Comparative example 1
Prescription:
Preparation method:
(1) it River Bank Stability: weighs starch 14.4g and is added in 480mL water, heating stirring is prepared into starch slurry；It weighs benefit and cuts down sand
Class's 30.0g, 99.0g hydroxypropyl methylcellulose, Sucralose 0.9g, famille rose 0.03g are added in above-mentioned solution, are stirred, and are taken out true
Sky is prepared into uniform razaxaban suspension slurries to 0.07-0.09Mpa bubble removing.
(2) be coated with drying: 188 μm of polyester films of installation are opened the continuous coating machine of MBCD1.3 type (German OPTIMAGS), 70 ± 5 DEG C
Dry, adjusting coating thickness makes 70 μm of film after drying.
(3) cutting packaging: gained film is cut with 10mg/ piece specification, and is taken off from polyester film, is packed using compound membrane bag.
Comparative example 2
Prescription:
Preparation method:
(1) River Bank Stability: weighing hydroxypropyl methylcellulose 87.0g and be added in 350mL water, stirring to dissolution；Weigh razaxaban
25.0g, hydroxypropylcellulose 16.0g, Macrogol 600 5.0g, Sucralose 0.6g, di-iron trioxide yellow 0.03g are added to
In above-mentioned solution, stirring stands 12h bubble removing, is prepared into uniform razaxaban suspension slurries.
(2) be coated with drying: 188 μm of polyester films of installation are opened the continuous coating machine of MBCD1.3 type (German OPTIMAGS), 70 ± 5 DEG C
Dry, adjusting coating thickness makes 70 μm of film after drying.
(3) cutting packaging: gained film is cut with 10mg/ piece specification, and is taken off from polyester film, is packed using compound membrane bag.
Comparative example 3
Compare research for convenience of with embodiment, buy listed razaxaban tablet (manufacturer: Bayer pharmacy,
Batch: BXG9601) as a comparison case 3.
Embodiment 7
Difference in thickness measurement
10 razaxaban oral quick-dissolving film preparations are respectively taken in embodiment 1-3, are measured using thickness gauge (precision 0.001mm),
Calculate average thickness.(unit: μm)
| Number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | It is average |
| Embodiment 1 | 70 | 68 | 70 | 71 | 70 | 69 | 68 | 69 | 69 | 70 | 69.4 |
| Embodiment 2 | 85 | 84 | 83 | 85 | 85 | 84 | 85 | 85 | 83 | 85 | 84.4 |
| Embodiment 3 | 100 | 100 | 100 | 98 | 100 | 101 | 101 | 100 | 99 | 99 | 99.8 |
The results show that preparation process of the present invention can get the razaxaban oral quick-dissolving film preparation of different-thickness and have excellent
Caliper uniformity.
Embodiment 8
Measuring Mechanical Properties
Film in Example 1-3 and comparative example 1-2 with reference to YBB60322012 " tensile property measuring method " and combines this
Invention film feature, using XLW Tensile Tester (Labthink Instruments Co., Ltd.), measuring method is as follows: will everywhere
Square film be divided into length 10cm(remove both ends effective length), width 1cm at item, both ends are clipped on tester, with
50mm/min speed tensile measures tensile elongation, calculates extensibility (extensibility=tensile elongation/initial length × 100%).In parallel
Measurement is three times, as a result as follows.
The results show that the film for the filmogen preparation that the present invention uses has excellent relative to other filmogens
Mechanical performance can retain integrality of the film in production, transport and storing process, reduce possible production during production and transportation
The risk of raw quality problems.
Embodiment 9
In Vitro Dissolution curve determination
3 razaxaban piece of razaxaban oral quick-dissolving film preparation 12 (10mg specification) and comparative example prepared by Example 3
Agent 12, referring to dissolution method (two the second methods of annex X C of Chinese Pharmacopoeia version in 2010).Experiment condition are as follows:
Acetate buffer (pH=4.5,0.2%SDS), hydrochloric acid solution (pH=1.0,0.2%SDS), water (0.2%SDS), phosphate
Buffer (pH=6.8,0.2%SDS) 900mL is dissolution medium, and revolving speed 75rpm is sampled respectively at different time points, using height
The measurement of effect liquid phase chromatogram method, obtains the dissolution data of difference.
Dissolution curve is as shown in Figs 1-4: comparing commercially available razaxaban tablet (comparative example 3), benefit prepared by the present invention is cut down
Husky class's oral quick-dissolving film preparation dissolution is fast, works rapid.
Embodiment 10
Influence factor and study on the stability
1. influence factor is tested
Razaxaban oral quick-dissolving film preparation and 3 razaxaban tablet of comparative example prepared by Example 3 is respectively in strong illumination
It is placed under conditions of (5500Lx ± 500Lx), high temperature (60 DEG C ± 2 DEG C), high humidity (relative humidity 92.5%, 25 DEG C), in 5,10 days
Sample detection key index investigates stability.Detection method is referring to razaxaban piece import registered standard (JX20080077), tool
Body result of study is as follows:
2. stability study
Example 1 ~ 3 prepare razaxaban oral quick-dissolving film preparation and 3 razaxaban tablet of comparative example be individually positioned in 40 DEG C,
Acceleration for stabilization Journal of Sex Research is carried out under RH75%, respectively at 0 month, March and sample detection key index in June, investigates stability.Specifically
Result of study is as follows:
By the above influence factor and accelerated stability test the results show that razaxaban oral instant membrane prepared by the present invention
Every Key Quality Indicator do not occur significant change, have good stability.
Claims (10)
1. a kind of razaxaban oral quick-dissolving film preparation, by razaxaban 1-40%, water soluble polymer 20-90% and pharmacy
Upper acceptable additive composition, is indicated with the percentage of film weight.
2. razaxaban oral quick-dissolving film preparation according to claim 1, it is characterised in that the water soluble polymer polymerization
Object is selected from polyvinyl alcohol, polyvinyl alcohol polyethylene glycol copolymer and polyvinyl alcohol mixture, polyvinyl alcohol polyethylene glycol copolymer
One kind.
3. razaxaban oral quick-dissolving film preparation according to claim 1, it is characterised in that described pharmaceutically acceptable to add
Adding agent includes filler 0-40%, plasticizer 0-20%, is indicated with the percentage of film weight.
4. razaxaban oral quick-dissolving film preparation according to claim 1, it is characterised in that described pharmaceutically acceptable to add
Adding agent can further comprise corrigent 0-10%, pigment 0-5%, be indicated with the percentage of film weight.
5. razaxaban oral quick-dissolving film preparation according to claim 3, it is characterised in that the filler is selected from starch, pre-
The one or more of gelling starch, lactose, low-substituted hydroxypropyl cellulose.
6. razaxaban oral quick-dissolving film preparation according to claim 3, it is characterised in that the plasticizer is selected from glycerol, gathers
Ethylene glycol, propylene glycol, phthalic acid ester, triethyl citrate, glyceryl triacetate, median chain triglyceride oil, castor oil one
Kind is several.
7. razaxaban oral quick-dissolving film preparation according to claim 4, it is characterised in that the corrigent is selected from sucrose, three
The one or more of chlorine sucrose, aspartame, acesulfame potassium, Mint Essence, cherry essence, fragrant citrus essence, citric acid.
8. razaxaban oral quick-dissolving film preparation according to claim 4, it is characterised in that the pigment is selected from sunset yellow, rouge
Rouge is red, iron oxide.
9. a kind of razaxaban oral quick-dissolving film preparation preparation method, comprising the following steps:
(1) River Bank Stability: water soluble polymer is added to the water by a., and stirring is to being dissolved into clear solution；B. by medicine
Object and additive are added in step (a) acquired solution, are dispersed with stirring uniformly and remove bubble, and uniform drug slurries are made；
(2) it is coated with drying: drug slurry being uniformly coated on back lining materials, 60-90 DEG C dries to obtain film；
(3) cutting packaging: film is cut into unit dose and is packed after being taken off from back lining materials.
10. razaxaban oral instant membrane preparation method according to claim 9, it is characterised in that the back in the step
Lining material is polyester film.
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