CN105919962A - Dabigatran tablet, and preparation method and application thereof - Google Patents
Dabigatran tablet, and preparation method and application thereof Download PDFInfo
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- CN105919962A CN105919962A CN201510958251.5A CN201510958251A CN105919962A CN 105919962 A CN105919962 A CN 105919962A CN 201510958251 A CN201510958251 A CN 201510958251A CN 105919962 A CN105919962 A CN 105919962A
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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Abstract
The present invention provides a dabigatran tablet, including a dabigatran layer, an organic acid layer compounded on the surface of the dabigatran layer. The organic acid layer includes organic acid and a sustained-release material; the organic acid is citric acid or tartaric acid; the sustained-release material is one or more of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose and hydroxyethyl cellulose; the dabigatran layer includes dabigatran and a pharmaceutically acceptable salt thereof; the content of the organic acid is 20wt%-50wt%; and the content of the slow release material is 5wt%-20wt%. The organic acid in the dabigatran tablet can release at a constant speed or slowly, thereby reducing the stimulation and injury of gastrointestinal drugs, but does not affect the bioavailability of the drug. At the same time, the preparation method is more simple and easy to operate, reduces the production cost, and is easy to realize industrialization.
Description
Technical field
The present invention relates to technical field of medicine, particularly relate to a kind of dabigatran etcxilate tablet and preparation thereof
Method.
Background technology
Dabigatran etcxilate, as shown in compounds I, is a kind of newly synthesized direct thrombin inhibitor, is
The prodrug of dabigatran, belongs to the thrombin inhibitor of non-peptides.Oral after gastrointestinal absorption, at body
Inside it is converted into the dabigatran with direct anticoagulant active.Dabigatran is incorporated into the fiber egg of thrombin
White specific binding site, stops Fibrinogen to be cracked into fibrin, thus has blocked blood coagulation waterfall net
The final step of network and thrombosis.Dabigatran can dissociate from fibrin one thrombin coalition,
Play reversible anticoagulation.
After dabigatran etcxilate oral medication, absolute bioavailability is 3%～7%, and blood drug level is the fastest at mouth
Take 1h and reach peak, half-life 14～17h.Dabigatran etcxilate is at pH > 4.0 time the most insoluble, sour environment has
It is beneficial to dabigatran etcxilate solution absorption.
At present, on market, the dabigatran etcxilate of supply only has capsule.Patent CN100528157 discloses
A kind of containing organic acid capsule core, sealing coat and dabigatran etcxilate and the compositions of the medicated layer of salt, this combination
Thing increases dissolving and the absorption of dabigatran etcxilate by organic acid particles, thus increases its bioavailability.
But, pharmaceutical composition disclosed in above-mentioned patent at least needs four steps to prepare: preparation is containing acid
Core material, applies sealing coat, applies the materials such as active material layer, coating film forming, plasticising, pigment, so
Rear filling is to hard capsule.Core material containing acid is not only required higher by this technique, needs the crystalline substance of certain diameter
Body or subsphaeroidal granule, and complex operation.Most important, capsule disclosed in above-mentioned patent, organic
After acid is with drug release, it is easily formed local low ph environment and damages gastrointestinal tract.
Summary of the invention
In view of this, the technical problem to be solved in the present invention be to provide a kind of dabigatran etcxilate tablet and
Preparation method, organic acid can constant speed or discharge slowly, and then reduce medicine and gastrointestinal stimulated and damages
Wound.
The invention provides a kind of dabigatran etcxilate tablet, including:
Dabigatran ester layer；
It is compound in organic acid layer on dabigatran ester layer surface；
Described organic acid layer includes machine acid and slow-release material；
Described organic acid is the acid of Chinese holly edge and/or tartaric acid；
Described slow-release material is carboxy-propyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl
Any one or more in cellulose and hydroxyethyl cellulose；
Described dabigatran ester layer includes dabigatran etcxilate and pharmaceutically acceptable salt thereof；
Described organic acid content is 20wt%～50wt%；
Described slow-release material content is 5wt%～20wt%.
Preferably, in described tablet, described organic acid content is 25wt%～40wt%.
Preferably, in described tablet, described slow-release material content is 8wt%～15wt%.
Preferably, in described tablet, described dabigatran etcxilate and pharmaceutically acceptable salt content thereof are
5wt%～50wt%.
Preferably, described slow-release material is hydroxypropyl methyl cellulose or hydroxyethyl cellulose.
Preferably, described organic acid layer is compound in described dabigatran ester layer upper surface and/or lower surface.
Preferably, adjuvant layer is also included between described organic acid layer and described dabigatran ester layer.
Preferably, described tablet also includes coating.
Preferably, described organic acid layer also includes diluent and lubricant；Described dabigatran ester layer is also wrapped
Include diluent, disintegrating agent and lubricant.
Present invention also offers the preparation method of a kind of dabigatran etcxilate tablet, including:
A) by organic acid and slow release material mixing the most also dry granulation, organic acid particles is obtained；
B) by dabigatran etcxilate and pharmaceutically acceptable salt thereof and adjuvant mix homogeneously dry granulation,
To dabigatran etcxilate granule；
C) organic acid particles and dabigatran etcxilate granule are passed through bi-layer tablet press tabletting；Or by three layers
Tabletting machine, intermediate layer is dabigatran ester layer, and remaining two-layer is organic acid layer；Or by three layers
Tabletting machine, intermediate layer is adjuvant layer, and remaining two-layer is respectively organic acid layer and dabigatran ester layer.
Compared with prior art, the invention provides a kind of dabigatran etcxilate tablet, including: dabigatran
Ester layer；It is compound in organic acid layer on dabigatran ester layer surface；Described organic acid layer includes machine acid and eases up
Release material；Described organic acid is the acid of Chinese holly edge and/or tartaric acid；Described slow-release material be carboxy-propyl cellulose,
Any one in hydroxypropyl methyl cellulose, methylcellulose, ethyl cellulose and hydroxyethyl cellulose
Or it is multiple；Described dabigatran ester layer includes dabigatran etcxilate and pharmaceutically acceptable salt thereof；Described have
Machine acid content is 20wt%～50wt%；Described slow-release material content is 5wt%～20wt%.
The dabigatran etcxilate tablet that the present invention provides, organic acid can constant speed or discharge slowly, and then reduce
Gastrointestinal is stimulated and damage by medicine, does not interferes with the bioavailability of medicine simultaneously.Meanwhile, its system
Preparation Method is the easiest to be easily operated, and reduces production cost, it is easier to realize industrialization.
Accompanying drawing explanation
Fig. 1 is the embodiment of the present application 1～4 and the tablet of comparative example 1～2 preparation and commercially available dabigatran etcxilate
The pH value curve comparison diagram of capsule；
Fig. 2 is the embodiment of the present application 1～4 and the tablet of comparative example 1～2 preparation and commercially available dabigatran etcxilate
The stripping curve comparison diagram of capsule.
Detailed description of the invention
The invention provides a kind of dabigatran etcxilate tablet, including:
Dabigatran ester layer；
It is compound in organic acid layer on dabigatran ester layer surface；
Described organic acid layer includes machine acid and slow-release material；
Described organic acid is the acid of Chinese holly edge and/or tartaric acid；
Described slow-release material is carboxy-propyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl
Any one or more in cellulose and hydroxyethyl cellulose；
Described dabigatran ester layer includes dabigatran etcxilate and pharmaceutically acceptable salt thereof；
Described organic acid content is 20wt%～50wt%；
Described slow-release material content is 5wt%～20wt%.
The dabigatran etcxilate tablet that the present invention provides, organic acid can constant speed or discharge slowly, and then reduce
Gastrointestinal is stimulated and damage by medicine, does not interferes with the bioavailability of medicine simultaneously.Meanwhile, its system
Preparation Method is the easiest to be easily operated, and reduces production cost, it is easier to realize industrialization.
The dabigatran etcxilate tablet that the present invention provides includes dabigatran ester layer.
Described dabigatran ester layer includes dabigatran etcxilate and pharmaceutically acceptable salt thereof.
The content of described dabigatran etcxilate and pharmaceutically acceptable salt thereof is preferably 5wt%～50wt%, more excellent
Electing 10wt%～40wt% as, in some embodiments of the invention, described content is 6wt%, 23wt%
Or 33wt%.
Currently preferred, described dabigatran ester layer also includes: diluent, disintegrating agent and lubricant.
Described diluent is preferably microcrystalline Cellulose, lactose, mannitol, starch, amylum pregelatinisatum and wheat
Any one in any one or more in bud dextrin, more preferably microcrystalline Cellulose, starch and lactose
Plant or multiple.
The content of described diluent is preferably 10wt%～50wt%, more elects 14wt%～40wt% as, at this
In some specific embodiment of invention, described content is 14.6wt%, 21.3wt%, 39.9wt%.
Described disintegrating agent is preferably sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose and friendship
Any one or more in connection polyvidone；More preferably sodium carboxymethyl cellulose and/or polyvinylpolypyrrolidone.
The content of described disintegrating agent is preferably 1wt%～4wt%, in some embodiments of the invention,
Described content is 1.6wt%, 1.8wt%, 3.4wt%.
Described lubricant is preferably in Pulvis Talci, magnesium stearate, fumaric acid sodium stearate and micropowder silica gel
Any one or more, more preferably magnesium stearate.
The content of described lubricant is preferably 0.1wt%～0.3wt%, in some embodiments of the invention
In, described content is 0.2wt%, 0.16wt%, 0.3wt%.
The dabigatran etcxilate tablet that the present invention provides also includes being compound in having of described dabigatran ester layer surface
Machine acid layer.
Described organic acid layer includes machine acid and slow-release material.
Described organic acid is preferably the acid of Chinese holly edge and/or tartaric acid.
The content of described organic acid is preferably 20wt%～50wt%, more preferably 25wt%～40wt%,
In some embodiments of the invention, its content is 25wt%, 33wt% or 28wt%.
Described slow-release material be preferably carboxy-propyl cellulose, hydroxypropyl methyl cellulose, methylcellulose,
Any one or more in ethyl cellulose and hydroxyethyl cellulose；More preferably hydroxypropyl methyl fiber
Element or hydroxyethyl cellulose；Most preferably hydroxypropyl methyl cellulose.
The content of described slow-release material is preferably 5wt%～20wt%, more preferably 8wt%～15wt%,
In some embodiments of the invention, its content is 11.6wt%, 15wt%.
Currently preferred, described organic acid layer also includes diluent and lubricant.
Described diluent is preferably microcrystalline Cellulose, lactose, mannitol, starch, amylum pregelatinisatum and wheat
Any one or more in bud dextrin, more preferably microcrystalline Cellulose and/or amylum pregelatinisatum.
The content of described diluent is preferably 5wt%～15wt%, in some embodiments of the invention,
Described content is specially 5.1wt%, 13.7wt%.
Described lubricant is preferably in Pulvis Talci, magnesium stearate, fumaric acid sodium stearate and micropowder silica gel
Any one or more, more preferably magnesium stearate and/or micropowder silica gel.
The content of described lubricant is preferably 0.2wt%～2.3wt%, in some embodiments of the invention
In, described content is 2.3wt%, 0.3wt%.
The dabigatran etcxilate tablet that the present invention provides can be bilayer tablet, and now, described organic acid layer is multiple
Together in described dabigatran ester layer upper surface or lower surface.
The dabigatran etcxilate tablet that the present invention provides can be tri-layer tablets, and now, described organic acid layer is multiple
Together in described dabigatran ester layer upper surface and lower surface.
Currently preferred, also include adjuvant layer between described organic acid layer and described dabigatran ester layer.
In some embodiments of the invention, described dabigatran etcxilate tablet includes organic acid layer, multiple
Together in the adjuvant layer on described organic acid layer surface, it is compound in the dabigatran ester layer on described adjuvant layer surface.
Described adjuvant layer by pharmaceutically acceptable possess make the customary adjuvant of tabletting properties and form.
Preferably, the dabigatran etcxilate tablet that the present invention provides also includes coating.
Described coating material is preferably Opadry II film coating pre-mix dose series.
Present invention also offers the preparation method of a kind of dabigatran etcxilate tablet, including:
A) by organic acid and slow release material mixing the most also dry granulation, organic acid particles is obtained；
B) by dabigatran etcxilate and pharmaceutically acceptable salt thereof and adjuvant mix homogeneously dry granulation,
To dabigatran etcxilate granule；
C) organic acid particles and dabigatran etcxilate granule are passed through bi-layer tablet press tabletting, obtain bilayer tablet；
Or by three laminate machine tablettings, intermediate layer is dabigatran ester layer, and remaining two-layer is organic acid layer,
Obtain tri-layer tablets；Or by three laminate machine tablettings, intermediate layer is adjuvant layer, remaining two-layer is respectively
For organic acid layer and dabigatran ester layer, obtain tri-layer tablets.
Above-mentioned steps A), B) order there is no successively.
Above-mentioned steps A) in can also add diluent and lubricant, described diluent, lubricant and
Content ibid, does not repeats them here.
Described lubricant adds after preferably pelletizing.
Described step B) in, described adjuvant is preferably diluent, disintegrating agent and lubricant, described dilution
Agent, disintegrating agent and lubricant and content thereof ibid, do not repeat them here.
Described lubricant can add together with other adjuvants, it is also possible to adds after granulation.
Currently preferred, described step C) after also include the step of coating.
In order to further illustrate the present invention, the dabigatran etcxilate sheet present invention provided below in conjunction with embodiment
Agent and preparation method thereof is described in detail.
Embodiment 1
By table 1 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Divide after making granule, be pressed into double-layer tablet, then use Opadry II film coating pre-mix dose coating material to enter
Row coating.
Table 1 embodiment 1 component proportion
Embodiment 2
By table 2 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Divide after making granule, be pressed into double-layer tablet.
Table 2 embodiment 2 component proportion
Embodiment 3
By table 3 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Dividing and make granule, blank auxiliary layer uses vertical compression type adjuvant mix homogeneously, then by three kinds of materials compactings
Become three-layer tablet, then use Opadry II film coating pre-mix dose coating material to be coated.
Table 3 embodiment 3 component proportion
Embodiment 4
By table 4 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Divide after making granule, be pressed into double-layer tablet, then use Opadry II film coating pre-mix dose coating material to enter
Row coating.
Table 4 embodiment 4 component proportion
Comparative example 1
By table 5 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Divide after making granule, be pressed into double-layer tablet, then use Opadry II film coating pre-mix dose coating material to enter
Row coating.
Table 5 comparative example 1 component proportion
Comparative example 2
By table 6 ingredients listed, by dry granulation respectively by each group of each for dabigatran etcxilate component, organic acid
Divide after making granule, be pressed into double-layer tablet.
Table 6 comparative example 2 component proportion
Embodiment 5 study on the stability result
Tablet prepared by embodiment 1～4 is placed in relative humidity 75% ± 5%RH, the acceleration that temperature is 40 DEG C ± 2 DEG C
Under experimental condition, and it is placed in relative humidity 60% ± 5%RH, the long term test condition that temperature is 30 DEG C ± 2 DEG C
Lower placement, result shows: the present invention provide dabigatran etcxilate tablet accelerate 6 months, long-term 24 months
Steady quality, character, dissolution, content, has the primary quality measure such as related substance all without notable change.
Composition pH measurement result after the release of embodiment 6 organic acid
Use dissolution test system, with 900ml water as medium, at temperature 37 DEG C, rotating speed 100rpm bar
Under part, by embodiment 1～4 and the tablet of comparative example 1～2 preparation and commercially available dabigatran etcxilate capsule put into
Stripping rotor, and in different time points sampling and measuring solution ph.The results are shown in Table 7 and Fig. 1, table 7 is this
Composition pH measurement result after application organic acid release, Fig. 1 is the embodiment of the present application 1～4 and compare
The tablet of example 1～2 preparation and the pH value curve comparison diagram of commercially available dabigatran etcxilate capsule.
Composition pH measurement result after the release of table 7 the application organic acid
By table 7 and Fig. 1 it can be seen that the application is by carrying out organic acid, slow-release material and ratio thereof
Limit, the organic acid in the dabigatran etcxilate tablet of preparation can slowly discharge, and meet pH value of blood want
Ask.
Embodiment 7 In Vitro Dissolution curve determination result
Use dissolution test system, with 900ml 0.01mol/L hydrochloric acid solution as dissolution medium, in temperature
37 DEG C, under the conditions of rotating speed 100rpm, by embodiment 1～4 and the tablet of comparative example 1～2 preparation and commercially available
Dabigatran etcxilate capsule input stripping rotor, and in different time points sampling and measuring dabigatran etcxilate dissolution also
Draw stripping curve.The results are shown in Table 8 and Fig. 2, table 8 is the application compositions stripping curve measurement result,
Fig. 2 is the embodiment of the present application 1～4 and the tablet of comparative example 1～2 preparation and commercially available dabigatran etcxilate capsule
Stripping curve comparison diagram.
Table 8 the application compositions stripping curve measurement result
By table 8 and Fig. 2 it can be seen that the dabigatran etcxilate tablet prepared of the application, slow at organic acid
While release, not interfering with the release behavior of principal agent dabigatran etcxilate, its In Vitro Dissolution curve reaches with former
More basically identical than adding group ester gum capsule.
The explanation of above example is only intended to help to understand method and the core concept thereof of the present invention.Should
Point out, for those skilled in the art, under the premise without departing from the principles of the invention,
The present invention can also be carried out some improvement and modification, these improve and modification also falls into right of the present invention and wants
In the protection domain asked.
Claims (10)
1. a dabigatran etcxilate tablet, including:
Dabigatran ester layer；
It is compound in organic acid layer on dabigatran ester layer surface；
Described organic acid layer includes machine acid and slow-release material；
Described organic acid is the acid of Chinese holly edge and/or tartaric acid；
Described slow-release material is carboxy-propyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl
Any one or more in cellulose and hydroxyethyl cellulose；
Described dabigatran ester layer includes dabigatran etcxilate and pharmaceutically acceptable salt thereof；
Described organic acid content is 20wt%～50wt%；
Described slow-release material content is 5wt%～20wt%.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that in described tablet,
Described organic acid content is 25wt%～40wt%.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that in described tablet,
Described slow-release material content is 8wt%～15wt%.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that in described tablet,
Described dabigatran etcxilate and pharmaceutically acceptable salt content thereof are 5wt%～50wt%.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that described slow-release material
For hydroxypropyl methyl cellulose or hydroxyethyl cellulose.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that described organic acid layer
It is compound in described dabigatran ester layer upper surface and/or lower surface.
Dabigatran etcxilate tablet the most according to claim 6, it is characterised in that described organic acid layer
And also include adjuvant layer between described dabigatran ester layer.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that described tablet also wraps
Include coating.
Dabigatran etcxilate tablet the most according to claim 1, it is characterised in that described organic acid layer
Also include diluent and lubricant；Described dabigatran ester layer also includes diluent, disintegrating agent and lubricant.
10. a preparation method for dabigatran etcxilate tablet, including:
A) by organic acid and slow release material mixing the most also dry granulation, organic acid particles is obtained；
B) by dabigatran etcxilate and pharmaceutically acceptable salt thereof and adjuvant mix homogeneously dry granulation,
To dabigatran etcxilate granule；
C) organic acid particles and dabigatran etcxilate granule are passed through bi-layer tablet press tabletting；Or by three layers
Tabletting machine, intermediate layer is dabigatran ester layer, and remaining two-layer is organic acid layer；Or by three layers
Tabletting machine, intermediate layer is adjuvant layer, and remaining two-layer is respectively organic acid layer and dabigatran ester layer.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107970225A (en) * | 2017-12-22 | 2018-05-01 | 重庆植恩药业有限公司 | A kind of dabigatran etcxilate solid lipid nano granule and preparation method thereof |
| EP3332771A1 (en) * | 2016-12-07 | 2018-06-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Multilayered tablet compositions of dabigatran |
| JP2018104425A (en) * | 2016-12-26 | 2018-07-05 | 日本ケミファ株式会社 | Tablet containing dabigatran etexilate or a pharmaceutically acceptable salt thereof |
| WO2018197613A1 (en) * | 2017-04-27 | 2018-11-01 | Boehringer Ingelheim International Gmbh | Tablet comprising dabigatran etexilate or pharmaceutically acceptable salt thereof and method of producing same |
| WO2019151966A3 (en) * | 2017-12-28 | 2019-10-10 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical tablet compositions of dabigatran |
| JP2020147542A (en) * | 2019-03-14 | 2020-09-17 | 日本ケミファ株式会社 | Multilayer tablet comprising dabigatran etexilate or pharmaceutically acceptable salt thereof |
| JP2020180099A (en) * | 2019-04-26 | 2020-11-05 | 沢井製薬株式会社 | Dabigatran etexylate methanesulfonate formulation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3332771A1 (en) * | 2016-12-07 | 2018-06-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Multilayered tablet compositions of dabigatran |
| WO2018104387A1 (en) * | 2016-12-07 | 2018-06-14 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Multilayered tablet compositions of dabigatran |
| JP2018104425A (en) * | 2016-12-26 | 2018-07-05 | 日本ケミファ株式会社 | Tablet containing dabigatran etexilate or a pharmaceutically acceptable salt thereof |
| WO2018197613A1 (en) * | 2017-04-27 | 2018-11-01 | Boehringer Ingelheim International Gmbh | Tablet comprising dabigatran etexilate or pharmaceutically acceptable salt thereof and method of producing same |
| JP2020520892A (en) * | 2017-04-27 | 2020-07-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Tablet containing dabigatran etexilate or a pharmaceutically acceptable salt thereof and method for producing the same |
| CN107970225A (en) * | 2017-12-22 | 2018-05-01 | 重庆植恩药业有限公司 | A kind of dabigatran etcxilate solid lipid nano granule and preparation method thereof |
| CN107970225B (en) * | 2017-12-22 | 2022-06-03 | 植恩生物技术股份有限公司 | Dabigatran etexilate solid lipid nanoparticle and preparation method thereof |
| WO2019151966A3 (en) * | 2017-12-28 | 2019-10-10 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical tablet compositions of dabigatran |
| JP2020147542A (en) * | 2019-03-14 | 2020-09-17 | 日本ケミファ株式会社 | Multilayer tablet comprising dabigatran etexilate or pharmaceutically acceptable salt thereof |
| JP2020180099A (en) * | 2019-04-26 | 2020-11-05 | 沢井製薬株式会社 | Dabigatran etexylate methanesulfonate formulation |
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| CN105919962B (en) | 2019-01-18 |
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