CN105343887B - A kind of eszopiclone oral instant membrane and preparation method thereof - Google Patents
A kind of eszopiclone oral instant membrane and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of eszopiclone oral quick-dissolving film preparation and preparation method thereof.The main component of the film includes eszopiclone inclusion compound, filmogen, filler, plasticizer, flavouring and antioxidant；Its preparation process includes：(1) eszopiclone inclusion compound is prepared；(2) blank glue is prepared；(3) eszopiclone drug containing glue is prepared；(4) coating of drug containing glue, drying process.The oral instant membrane can not only cover the bitter taste of eszopiclone, without with water delivery service, suitable for children, old man and the insomniac there are dysphagia；, can flash melt, bioavilability be high in the oral cavity and pliability is good, is not easy friability.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of to be combined inclusion technique with oral instant membrane technology
Formulation and preparation method thereof, further relates to a kind of eszopiclone oral instant membrane and preparation method thereof.
Background technology
Insomnia is a kind of form of expression of sleep-disorder, and clinical manifestation is difficulty falling asleep, and sleep is not deep, easily wakes up with a start, early awakening,
Dreaminess, it is tired after waking up, or lack clear-headed sense, daytime is drowsy etc..When sleep wretched insufficiency when, immune function of human body will be caused low
With a variety of diseases.Data shows according to the statistics of the World Health Organization, and the people that the whole world has nearly 1/4 has been subject to different degrees of insomnia to be stranded
Disturb, the sleep quality that the U.S. there are about more than 8,000 ten thousand people is not good enough, and China also has more than 10% people, and there are sleep-disorder.Saved in society
Play today of quickening and intensified competition, insomnia has been increasingly becoming a kind of very universal phenomenon, also becomes countries in the world
One of hidden danger for seriously affecting publilc health of generally existing.
At present, common the hypnotic sedative agent such as barbiturates, Benzodiazepines of insomnia are treated, often with a variety of secondary works
With such as：Cause drowsiness, weak, dizzy, incoordination, temporary forgetting and disturbance of consciousness etc., be also possible to cause dusk when serious
Fan, respiration inhibition.In addition, it is also possible to produce tolerance and dependence.Although and Non-benzodiazepine somnifacient and benzene two
Nitrogen Zhuo class mechanism of drug action is similar, but its selectivity is stronger, acts only on certain hypotype of GABA acceptors, so makes it have
The effect of more preferable, less adverse reaction.Therefore, such medicine is received by clinic year by year, dosage steady-state growth, and this kind of medicine is main
There are zolpidem, zopiclone, Zaleplon etc..
Eszopiclone (Esopiclone) is the quick short-acting Non-benzodiazepine developed by Sepracor companies of the U.S.
Hypnotic sedative agent, is the dextrorotation individual isomer of zopiclone, his father's medicine zopiclone is by French Rhone-poulenc Rorer
Company is listed in exploitation in 1987 with racemic modification, belongs to clinical in country of more than 80, the world and regional list marketing at present
One of upper medicine most for insomnia.The medicine is used for short-term and chronic insomnia treatment, is improving sleep quality side
Face is similar to benzodiazepine, but residual effect and hangover phenomenon are fewer than benzodiazepine after medication, make for a long time
With without obvious drug resistance, additive and accumulative.The medicine is left zopiclone to the affinity of Benzodiazepine receptoroid
50 times, curative effect is stronger, toxicity is lower.Therefore, eszopiclone is ideal sedative hypnotic drug.
This product is tablet (1mg, 2mg and 3mg specification) in U.S.'s listing kind, and domestic commercially available kind is also tablet (rule
Lattice 3mg), it is domestic at present there was only the production of Jiangsu Tian Shili companies, trade name Wen Fei.Tablet is as common oral preparation, patient's clothes
Used time must use water delivery service, not only take inconvenience, be not easy to swallow, and absorption is slower, be not suitable for the elderly and exist to swallow
Difficult patient.Medicine for preferably treatment insomnia should can produce soporific function rapidly after administration before sleeping.Thus
Develop it is a kind of can quick acting, dosage form convenient to take, good patient compliance be very necessary.
Patent CN02156852.9 discloses zopiclone oral disnitegration tablet for the treatment of insomnia and preparation method thereof, Jiang Youzuo
Clone is prepared into oral disnitegration tablet, although can solve the above problems to a certain extent, is needed in production process using high
The easy moisture absorption of expensive lyophilized technique, high energy consumption, and preparation, friability is high, is required for pharmaceutical packing, storage, transport extremely tight
Lattice.In addition, often there are sand type, patient's poor compliance when oral disnitegration tablet is taken.And oral quick-dissolving film preparation (oral fast
Dissolving films) pliability is good, and friability is not easy, ensure that the accuracy of dosage；It is in good taste, without being sent with water
Clothes, flash melt, rapid-onset, patient's compliance height, oral quick-dissolving film preparation can be children, the elderly and swallow tired in oral cavity
The medication of difficult insomniac provides a great convenience.In addition, oral quick-dissolving film preparation appearance is lightly easy to carry, preparation process
Simply, it is of low cost, it is adapted to large-scale production.Therefore, oral quick-dissolving film preparation is a kind of alternative conventional dosage forms such as solution, piece
Agent and the preferable novel form of capsule, will have a vast market prospect.
However, eszopiclone can produce extremely strong and lasting bitter taste in the oral cavity, if being directly made into mouth
The instant film of chamber, is difficult effective bitter taste for covering eszopiclone using the means such as flavouring are added.And use inclusion technique will
After eszopiclone is prepared into inclusion compound, its bitter taste not only can be effectively covered, it is water-soluble that it can also be improved.Therefore, first
The bitter taste of eszopiclone is covered using inclusion technique, oral quick-dissolving film preparation is then made into again, will can improve patient's
Compliance, so as to give full play to the clinical practice of eszopiclone.
The content of the invention
It is an object of the invention to provide one kind can in the oral cavity flash melt, absorb, conveniently take, patient's compliance
Good and preparation process is simple, oral quick-dissolving film preparation of low cost and preparation method thereof, with overcome existing for existing preparation to
The problem of medicine is inconvenient.
Technical scheme is as follows：
Eszopiclone oral instant membrane includes eszopiclone inclusion compound, filmogen and flavouring in the invention.Should
It can also include the one or more in filler, plasticizer or antioxidant in the molten film of mouth.
Wherein eszopiclone inclusion compound is made by eszopiclone and beta-cyclodextrin by spray drying process；Flavouring bag
Include acid, sweetener and essence.
The percentage by weight of each component is in eszopiclone oral instant membrane in the invention：
Preferably, the percentage by weight of each component is in eszopiclone oral instant membrane：
Wherein filmogen is selected from polyvinyl alcohol Mowiol 4-88 (PVAMowiol 4-88), HPC SL
(HPC-SL), hydroxypropyl methylcellulose E3, E5 and E15 (HPMC E3, HPMC E5 and HPMC E15), polyoxyethylene WSR N-80
In (PEO WSR N-80), polyvinyl alcohol polyethylene glycol copolymer and polyvinyl alcohol mixture (Kollicoat Protect)
One or more, above-mentioned filmogen is respectively provided with preferable filming performance, and property is stablized, and good water solubility can be molten by human body
Solution, absorb.
One or more of the acid in citric acid, malic acid, tartaric acid in flavouring in the present invention；Essence selects
One or more from menthol, orange flavor, lemon extract；Sweetener is Sucralose, the Sucralose be uniquely with
Sucrose is the functional sweetener of raw material, has a noenergy, and sugariness height, sweet taste is pure, it is highly safe the features such as, can effectively cover
The offending taste such as bitter, puckery is covered, is one of current classic functional sweetener.
Filler is selected from mannitol or sorbierite, the two is water-soluble preferably, and has refrigerant sense after dissolving, and can not only promote
The molten film of import quickly dissolves in the oral cavity, can also strengthen its mouthfeel；Plasticizer is selected from propane diols, glycerine, Tween 80, poly- second two
One or more in alcohol (PEG400), the plasticizer in the invention can improve the pliability of the molten film of mouth and to reduce its crisp
Property, it is very important component in the molten film prescription of mouth.
Antioxidant in the present invention is dibutyl hydroxy toluene (BHT), due to filmogen polyoxyethylene WSR N-80 couple
Oxygen is more sensitive, therefore, a small amount of antioxidant need to be added in prescription.
The preparation method of the eszopiclone oral instant membrane includes the following steps：
(1) beta-cyclodextrin and eszopiclone are weighed respectively, beta-cyclodextrin water are dissolved by heating into saturated solution, by the right side
Zopiclone after acetone solution with being slowly added into the saturated solution of beta-cyclodextrin, and 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, then
Solution is put and obtains eszopiclone inclusion compound powder after being spray-dried in spray dryer；
(2) by macromolecule filming material, it is dissolved in purified water under 60~70 DEG C of heating, stirring conditions, then adds successively
Enter filler, plasticizer, flavouring and antioxidant, white glue liquid of having leisure after stirring evenly；
(3) added after the eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water in step (2)
In blank glue, it is sufficiently stirred and is uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains right assistant
Clone drug containing glue；
(4) the drug containing glue in step (3) is stood and is coated on after removing bubble in PET film, after dry, film is cut
Into certain size, pack to obtain the final product.
The molar ratio that both eszopiclone and beta-cyclodextrin mix wherein in step (1) is 1:1；Beta-cyclodextrin is with water-soluble
The temperature of solution into saturated solution is 50~70 DEG C.
The solid content of drug containing glue described in step (3) is 15-30% (w/w)；Bubble removing method is to contain in step (4)
Medicine glue stands 6~8h under vacuum；Drying temperature is 60~80 DEG C.
In test, the inventors discovered that, the filming performance of macromolecule filming material, the mechanical performance of film, rate of dissolution
Deng closely related with the model of macromolecule filming material, such as using the HPMC of different model as filmogen when, filming performance compared with
It is good, but using HPMC E3 as filmogen, the film pliability of preparation is poor, and brittleness is stronger, and rate of dissolution is very fast, with HPMC
E15 is filmogen, and the film pliability of preparation is preferable, but rate of dissolution is slower；And the film prepared using HPMC E5 as filmogen
Rate of dissolution is very fast, and pliability is also preferable.Therefore, it is molten in order to prepare the mouth with good mechanical properties and very fast rate of dissolution
Film, it is necessary to the macromolecule filming material of suitable types is selected, can also be by the way of different model filmogen shares.
In addition, inventor also found, the compatibility of macromolecule filming material and plasticizer be it is selective, such as using PVA as
Filmogen, it is necessary to add a certain amount of plasticizer and just can guarantee that film strength and pliability, plasticizer can be propane diols, sweet
One or more in oil, Tween 80 and polyethylene glycol.But with polyoxyethylene (PEO) and polyvinyl alcohol polyethylene glycol copolymer with
When polyvinyl alcohol mixture (Kollicoat Protect) is filmogen, it is not required to add plasticizer in prescription, after addition on the contrary
The mechanical performance of film can be reduced or slow down the rate of dissolution of film.
Beneficial effects of the present invention are：
1) after eszopiclone is prepared into inclusion compound by the present invention using inclusion technique, its bitter taste not only can be effectively covered,
It is water-soluble that it can also be improved.
2) eszopiclone inclusion compound is prepared into oral instant membrane by the present invention using the molten membrane technology of mouth, convenient to take, is risen
Effect is rapid, in good taste, and patient's compliance is high, and the medication for the insomniac of children, old man and dysphagia is provided convenience.
3) eszopiclone oral instant membrane prepared by the present invention, pliability is good, is not easy friability；Appearance is light and handy, easy to take
Band；And simple production process, it is of low cost, it is adapted to large-scale production, has a vast market prospect
English abbreviation explanation
Brief description of the drawings
Fig. 1 is the stripping curve figure of eszopiclone oral instant membrane in embodiment 1-6.
Embodiment
The present invention makees further specifically eszopiclone oral instant membrane and preparation method thereof by following embodiments
It is bright, but the present invention is not limited in following embodiments.
Embodiment 1
Composition：
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), molar ratio is accurately weighed respectively as 1:1 beta-cyclodextrin 29.2g and eszopiclone 10.0g, β-ring is pasted
Essence is heated to 50 DEG C with water and is dissolved into saturated solution, by eszopiclone be slowly added into after 150ml acetone solutions above-mentioned β-
In the saturated solution of cyclodextrin, 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, is then put solution and is obtained after being spray-dried in spray dryer
Eszopiclone inclusion compound powder；
(2), recipe quantity Kollicoat Protect accurately are weighed, is dissolved in purifying under 60~70 DEG C of heating, stirring conditions
In water, malic acid, Sucralose and menthol are then sequentially added, white glue liquid of having leisure after stirring evenly；
(3), the eszopiclone inclusion compound powder in the step of taking recipe quantity (1) adds step after being uniformly dispersed with purified water
Suddenly in the blank glue in (2), it is sufficiently stirred and is uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly,
Eszopiclone drug containing glue is obtained, the solid content of glue is 30% (w/w)；
(4), drug containing glue in step (3) is stood into 6h to remove bubble under vacuum, then by glue-coating in
In PET film, after 80 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
Embodiment 2
Composition：
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), molar ratio is accurately weighed respectively as 1:1 beta-cyclodextrin 29.2g and eszopiclone 10.0g, β-ring is pasted
Essence is heated to 70 DEG C with water and is dissolved into saturated solution, by eszopiclone be slowly added into after 150ml acetone solutions above-mentioned β-
In the saturated solution of cyclodextrin, 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, is then put solution and is obtained after being spray-dried in spray dryer
Eszopiclone inclusion compound powder；
(2), recipe quantity PVA Mowiol 4-88 accurately are weighed, is dissolved in purified water under 60~70 DEG C of heating, stirring conditions
In, sorbierite, PEG400, citric acid, Sucralose and lemon extract are then sequentially added, white glue liquid of having leisure after stirring evenly；
(3), the eszopiclone inclusion compound powder in recipe quantity step (1) is taken to add step after being uniformly dispersed with purified water
(2) in the blank glue in, it is sufficiently stirred and is uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains
To eszopiclone drug containing glue, the solid content of glue is 20% (w/w)；
(4), the drug containing glue in step (3) is stood into 8h to remove bubble under vacuum, then by glue-coating
In in PET film, after 70 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
Embodiment 3
Composition：
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), molar ratio is accurately weighed respectively as 1:1 beta-cyclodextrin 29.2g and eszopiclone 10.0g, β-ring is pasted
Essence is heated to 60 DEG C with water and is dissolved into saturated solution, by eszopiclone be slowly added into after 150ml acetone solutions above-mentioned β-
In the saturated solution of cyclodextrin, 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, is then put solution and is obtained after being spray-dried in spray dryer
Eszopiclone inclusion compound powder；
(2), recipe quantity HPMC E5 accurately are weighed, is dissolved under 60~70 DEG C of heating, stirring conditions in purified water, then
Glycerine, tartaric acid, Sucralose and orange flavor are sequentially added, white glue liquid of having leisure after stirring evenly；
(3), added after the eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water in step (2)
Blank glue in, be sufficiently stirred and be uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains right assistant
Clone drug containing glue, the solid content of glue is 15% (w/w)；
(4), drug containing glue in step (3) is stood into 7h to remove bubble under vacuum, then by glue-coating in
In PET film, after 75 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
Embodiment 4
Composition：
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), molar ratio is accurately weighed respectively as 1:1 beta-cyclodextrin 29.2g and eszopiclone 10.0g, β-ring is pasted
Essence is heated to 65 DEG C with water and is dissolved into saturated solution, by eszopiclone be slowly added into after 150ml acetone solutions above-mentioned β-
In the saturated solution of cyclodextrin, 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, is then put solution and is obtained after being spray-dried in spray dryer
Eszopiclone inclusion compound powder；
(2), recipe quantity PEO WSR N-80 accurately are weighed, is dissolved under 60 DEG C of heating, stirring conditions in purified water, then
Citric acid, malic acid, Sucralose, lemon extract and BHT are sequentially added, white glue liquid of having leisure after stirring evenly；
(3), added after eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water in step (2)
In blank glue, it is sufficiently stirred and is uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains right assistant
Drug containing glue is cloned, the solid content of glue is 20% (w/w)；
(4), drug containing glue in step (3) is stood into 8h to remove bubble under vacuum, then by glue-coating in
In PET film, after 60 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
Embodiment 5
Composition：
Wherein eszopiclone inclusion compound is made of eszopiclone and beta-cyclodextrin.
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), technique is the same as embodiment 1；
(2), recipe quantity HPMC E3 and HPMC E15, PVA Mowiol 4-88 accurately are weighed, in 70 DEG C of heating, stirring bars
It is dissolved under part in purified water, then sequentially adds PEG 400, Tween-80, citric acid, Sucralose and lemon extract, stirring is equal
Have leisure after even white glue liquid；
(3), added after the eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water in step (2)
Blank glue in, be sufficiently stirred and be uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains right assistant
Clone drug containing glue, the solid content of glue is 20% (w/w)；
(4), drug containing glue in step (3) is stood into 7h to remove bubble under vacuum, then by glue-coating in
In PET film, after 80 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
Embodiment 6
Composition：
Wherein eszopiclone inclusion compound is 1 by molar ratio:The 1 spray-dried legal system of eszopiclone and beta-cyclodextrin
Into.
Preparation process：
(1), technique is the same as embodiment 2；
(2), recipe quantity HPC-SL accurately is weighed, is dissolved under 65 DEG C of heating, stirring conditions in purified water, then added successively
Enter sorbierite, propane diols, Tween-80, malic acid, Sucralose and orange flavor, white glue liquid of having leisure after stirring evenly；
(3), added after the eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water in step (2)
Blank glue in, be sufficiently stirred and be uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains right assistant
Clone drug containing glue, the solid content of glue is 25% (w/w)；
(4), drug containing glue in step (3) is stood into 6h to remove bubble under vacuum, then by glue-coating in
In PET film, after 65 DEG C of dryings, film is cut into certain size, is packed to obtain the final product.
7 quality evaluation test example 1 of embodiment dissolves time limit measure
Each 6 of film in Example 1-6, takes 1 every time, is gently placed in (37 ± 1) DEG C artificial saliva, stands shape
Under state, the time that this product is completely dissolved is observed.Required with reference to the disintegration time limited of similar type oral disintegrated tablet, if dissolution time is few
In 60 seconds, it is believed that the molten film of mouth of exploitation reaches rapidly-soluble target, and measurement result is shown in Table 1.
1 eszopiclone oral instant membrane of table dissolves time limit measurement result
As seen from the above table, with Kollicoat Protect, PVAMowiol 4-88, HPMC E5, PEO WSR N-80,
HPMC E3, E15 and PVAMowiol 4-88, HPC-SL are filmogen, and the film of preparation dissolves the time limit and meets the requirements, real
Apply example 1, embodiment 2 and embodiment 4 i.e. using Kollicoat Protect, PVA Mowiol 4-88 and PEO WSR N-80 as
During filmogen, the film of preparation can quickly dissolve in artificial saliva, so as to discharge medicine.
2 Erichsen test of test example
The not cut molten film of eszopiclone mouth prepared by Example 1-6 is appropriate, cuts 100mm × 20mm sizes
6, sample, sample edge must smooth, non-notch and damage, tensile property test is carried out on force detector is broken.
Before experiment, the measurer for being 0.001mm with precision first measures sample thickness, and the thickness of each sample should measure at 3 points,
Take arithmetic mean of instantaneous value.Film is placed on to the line of centres broken and in two fixtures, make sample and upper and lower fixture above and below force detector
Overlap, fixture is elastic suitable, and to prevent from being broken in sample slippage or fixture, the spacing of two fixtures is 60mm.With (100 ± 10)
The speed of mm/min starts tester, after sample fracture, reads tensile strength and elongation at break, measurement result are shown in Table 2.
2 eszopiclone oral instant membrane Erichsen test result of table
As seen from the above table, embodiment 4 is only by film tensile strength prepared by filmogen of PEO WSR N-80
9.2Mpa, mechanical performance are slightly worse；Film tensile strength prepared by other embodiment is all higher than 10Mpa (sizes：100mm×
20mm), the mechanical performance of film is preferable.
3 dissolution test of test example
Each 6 of the film of Example 1-6, is clamped with clip respectively, using dissolution method (Chinese Pharmacopoeia 2010
Two the 3rd methods of annex XC of year version) device, using the 0.1mol/L hydrochloric acid solutions of 250ml as dissolution medium, rotating speed is per minute 50
Turn, from test sample contacts dissolution medium, timing immediately, takes solution 5ml through 0.5,1,3,5,10,15min respectively, and mends equality of temperature
The blank dissolution medium of equivalent, after filtering with microporous membrane, takes subsequent filtrate to carry out HPLC measure, calculates the stripping quantity of every.Its
In Vitro Dissolution curve is shown in Fig. 1.
As seen from Figure 1, the In Vitro Dissolution of the molten film of eszopiclone mouth of the invention quickly, 3min, that is, dissolution more than 85%,
Dissolved substantially during 5min completely.
Dissolve time limit and mouthfeel evaluation test in 4 oral cavity of test example
Each 1 of the film of Example 1-6, by 6 molten films of healthy volunteer's test-meal eszopiclone mouth, everyone takes one
Piece, in the case where not drinking water, record is put into the solution time behind oral cavity, and mouthfeel is evaluated, and standards of grading are：0 point：
It is excellent without bitter taste, mouthfeel；1 point：There are slight bitter taste, good mouthfeel；2 points：Bitter taste is more apparent, and mouthfeel is general；3 points：There is strong hardship
Taste, poor taste, concrete outcome are shown in Table 3.
Dissolve time limit and mouthfeel evaluation result in 3 eszopiclone oral instant membrane oral cavity of table
From above-mentioned experimental result, the molten film of eszopiclone mouth prepared by embodiment 1-6 is in the oral cavity in 30 seconds
Dissolve completely.Using bulk pharmaceutical chemicals first are prepared into inclusion compound, right assistant can effectively be covered by adding the mode of appropriate flavouring
The bitter taste of clone, so as to improve the compliance of patient.
Claims (10)
1. a kind of eszopiclone oral instant membrane, it is characterised in that the eszopiclone oral instant membrane includes right assistant
Inclusion compound is cloned, filmogen and flavouring, the eszopiclone inclusion compound pass through spray by eszopiclone and beta-cyclodextrin
Mist seasoning is made.
A kind of 2. eszopiclone oral instant membrane according to claim 1, it is characterised in that the eszopiclone mouth
Chamber dissolving films further include the one or more in filler, plasticizer or antioxidant.
A kind of 3. eszopiclone oral instant membrane according to claim 1 or 2, it is characterised in that the flavouring bag
Include acid, sweetener and essence.
A kind of 4. eszopiclone oral instant membrane according to claim 1 or 2, it is characterised in that the right assistant gram
The percentage by weight of grand oral instant membrane each component is：
A kind of 5. eszopiclone oral instant membrane according to claim 1 or 2, it is characterised in that the right assistant gram
The preferable percentage by weight of each component is in grand oral instant membrane：
The sum of percentage by weight of each component is 100%.
6. a kind of eszopiclone oral instant membrane according to claim 3, it is characterised in that the filmogen is selected from
Polyvinyl alcohol Mowiol 4-88 (PVA Mowiol 4-88), HPC SL (HPC-SL), hydroxypropyl methylcellulose E3, E5
With E15 (HPMC E3, HPMC E5 and HPMC E15), polyoxyethylene WSR N-80 (PEO WSR N-80), the poly- second of polyvinyl alcohol
Diol copolymer and the one or more in polyvinyl alcohol mixture (Kollicoat Protect)；Acid in the flavouring
One or more of the taste agent in citric acid, malic acid, tartaric acid；The sweetener is Sucralose；The essence is selected from
One or more in menthol, orange flavor, lemon extract.
7. a kind of eszopiclone oral instant membrane according to claim 2, it is characterised in that the filler is selected from sweet
Reveal alcohol or sorbierite；The plasticizer is selected from one kind or several in propane diols, glycerine, Tween 80, polyethylene glycol 400 (PEG400)
Kind；The antioxidant is dibutyl hydroxy toluene (BHT).
8. a kind of eszopiclone oral instant membrane according to claim 1 or 2, its preparation method include the following steps：
(1) beta-cyclodextrin and eszopiclone are weighed respectively, beta-cyclodextrin water is dissolved by heating into saturated solution, by right assistant
For clone with being slowly added into after acetone solution in the saturated solution of beta-cyclodextrin, 4~6h is stirred in 65 DEG C of waters bath with thermostatic control, then will be molten
Liquid, which is put, obtains eszopiclone inclusion compound powder after spray drying in spray dryer；
(2) macromolecule filming material is dissolved in purified water under 60~70 DEG C of heating, stirring conditions, then sequentially adds flavoring
Agent, filler, plasticizer, antioxidant, white glue liquid of having leisure after stirring evenly；
(3) blank in step (2) is added after the eszopiclone inclusion compound powder in step (1) is uniformly dispersed with purified water
In glue, it is sufficiently stirred and is uniformly dispersed, 2~3min of high speed shear under 10000rpm, 4~5 times repeatedly, obtains eszopiclone
Drug containing glue；
(4) the drug containing glue in step (3) is stood and is coated on after removing bubble in PET film, after dry, film is cut into one
Fixed size, packs to obtain the final product.
A kind of 9. eszopiclone oral instant membrane according to claim 8, it is characterised in that the preparation method step
(1) molar ratio that both eszopiclone and beta-cyclodextrin mix in is 1:1；Beta-cyclodextrin is dissolved into the temperature of saturated solution with water
Spend for 50~70 DEG C.
A kind of 10. eszopiclone oral instant membrane according to claim 8, it is characterised in that the preparation method step
(3) solid content of drug containing glue described in is 15-30% (w/w)；Bubble removing method is in vacuum by drug containing glue in step (4)
Under the conditions of stand 6~8h；Drying temperature is 60~80 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510730634.7A CN105343887B (en) | 2015-10-30 | 2015-10-30 | A kind of eszopiclone oral instant membrane and preparation method thereof |
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| CN109381448A (en) * | 2017-08-04 | 2019-02-26 | 广州朗圣药业有限公司 | A kind of razaxaban oral quick-dissolving film preparation and preparation method thereof |
| KR20210033489A (en) * | 2018-07-11 | 2021-03-26 | 큐어 파마슈티컬 홀딩 코포레이션 | Rapid disintegrating oral film matrix |
| CN108743567A (en) * | 2018-08-24 | 2018-11-06 | 北京太阳升高科医药研究股份有限公司 | Molten film of galanthamine hydrobromide mouth and preparation method thereof |
| AU2021374831A1 (en) * | 2020-11-09 | 2023-06-29 | Lts Lohmann Therapie-Systeme Ag | Oral thin film |
| CN115400099A (en) * | 2021-05-26 | 2022-11-29 | 上海博志研新药物技术有限公司 | Carilazine oral film composition, preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010044736A1 (en) * | 2008-10-14 | 2010-04-22 | Mcneil Ab | Multi portion intra-oral dosage form and use thereof |
| CN102727452A (en) * | 2011-04-01 | 2012-10-17 | 成都康弘药业集团股份有限公司 | Eszopiclone-containing particle and its preparation method |
| CN103356509A (en) * | 2012-03-29 | 2013-10-23 | 刘毅佳 | Film agent containing zolpidem serving as main active component |
| CN104546806A (en) * | 2015-01-05 | 2015-04-29 | 万特制药(海南)有限公司 | Oral cavity instant film containing risperidone and preparation method for oral cavity instant film |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010044736A1 (en) * | 2008-10-14 | 2010-04-22 | Mcneil Ab | Multi portion intra-oral dosage form and use thereof |
| CN102727452A (en) * | 2011-04-01 | 2012-10-17 | 成都康弘药业集团股份有限公司 | Eszopiclone-containing particle and its preparation method |
| CN103356509A (en) * | 2012-03-29 | 2013-10-23 | 刘毅佳 | Film agent containing zolpidem serving as main active component |
| CN104546806A (en) * | 2015-01-05 | 2015-04-29 | 万特制药(海南)有限公司 | Oral cavity instant film containing risperidone and preparation method for oral cavity instant film |
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