CN106822006A - A kind of Apixaban tablet and preparation method thereof - Google Patents
A kind of Apixaban tablet and preparation method thereof Download PDFInfo
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- CN106822006A CN106822006A CN201610404486.4A CN201610404486A CN106822006A CN 106822006 A CN106822006 A CN 106822006A CN 201610404486 A CN201610404486 A CN 201610404486A CN 106822006 A CN106822006 A CN 106822006A
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- eliquis
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- apixaban tablet
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- magnesium stearate
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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
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The present invention provides a kind of Apixaban tablet, contain Eliquis raw material and pharmaceutic adjuvant, the X ray powder diffractions that wherein Eliquis raw material is represented with 2 θ angles are at 12.8 ± 0.2 °, 13.9 ± 0.2 °, 17.0 ± 0.2 °, 18.4 ± 0.2 °, 22.2 ± 0.2 °, there is characteristic peak at 26.9 ± 0.2 °, present inventors have unexpectedly found that, when by the D of Eliquis A crystal formations90At 40 85 μm, obtained Eliquis preparation dissolution rate change is very small, and dissolution rate is hardly changed by the change of particle diameter, has obtained the homogeneous Eliquis preparation of dissolution for control.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of Apixaban tablet and preparation method thereof.
Background technology
Eliquis, chemical name is 1- (4- methoxyphenyls) -7- oxos -6- [4- (2- oxo -1- piperidyls) benzene
Base] -4,5,6,7- tetrahydrochysene -1H- pyrazoles [3,4-c] pyridine-3-carboxamides, molecular formula is C25H25N5O4, structural formula is：
Eliquis are that a kind of potent, orally active reversible, direct, high selectivity Xa factor avtive spot suppresses
Agent, can suppress Xa factor that is free and being combined with thrombus, and suppress factor enzymatic activity.European drug administration and the U.S.
FDA have been approved by Apixaban tablet for prevent receive to select a time hip joint or knee replacements adult patients appearance vein
Thromboembolism (VTE) event, palsy and thrombus are prevented for NVAF patient, and for adult patient deep vein
The treatment of bolt and pulmonary embolism and the prevention of recurrent DVT and pulmonary embolism.Eliquis are white to pale yellow crystals type
Powder, non-ionic compound, under the conditions of physiological pH 1.2-6.8, the solubility in water is about 0.04mg/ml.
Patent CN104788448A discloses a kind of Eliquis crystal formation (for convenience of describing, hereinafter referred to as crystal formation A), and A is brilliant
Type with more preferable dissolubility, and will not occur crystal transfer compared with existing crystal formation during storage, ensure that
The quality stable homogeneous of different batches of product, and the content of wherein specific impurities is lower, with security higher.
Patent US6967208 discloses a series of coagulation factor xa inhibitors, wherein Eliquis are contained, and its
Illustrate that Eliquis can be administered with pharmaceutically useful medium, the form of the pharmaceutical composition of diluent or carrier.
Patent CN102770126A discloses a kind of particle mean size less than or equal to 89 μm of Eliquis particle and medicinal auxiliary
The composition of material, disclosing can prepare Eliquis particle and then preparation Apixaban tablet using wet method or dry granulation process
Agent.
Patent CN102908324A discloses a kind of increase and absorbs, and improves the Eliquis preparation of bioavilability, uses
Modern solid dispersion technology, disperses during Eliquis are added into 60 DEG C of molten polyethylene glycols 6000, is crushed after solidification cooling, obtains
Eliquis solid dispersions, its requirement to workshop in big production is higher, it is necessary to configure can not only heat but also having with stirring
The equipment and decompression drying equipment of standby refrigerating function, production difficulty are larger.Patent CN104095823A discloses a kind of Ah piperazine
The preparation method of husky class's tablet, the method is used first by Eliquis and water-soluble material co-grinding, then by mixture
Other auxiliary material direct tablet compressings are added, Eliquis tablet 15min could realize that dissolution rate is reached more than 80% obtained in the method,
Dissolution rate is slow and impurity content is high.
Dissolution rate is the key quality factors of oral solid formulation, affects medicine and absorbs in vivo, is distributed, is metabolized and arranges
Let out.Ensure dissolution rate homogeneity, be the key for ensureing drug effectiveness and security.And according to above-mentioned prior art, crystal formation, grain
The composition of auxiliary material has significant impact to the dissolution rate of Eliquis in degree, prescription, or even can produce interactive influence, because
This, it is necessary to develop a kind of Apixaban tablet of dissolution rate stable homogeneous.
The content of the invention
The present invention by Eliquis A crystal formations (crystal formation by patent CN104788448A disclosed in method carry out
Prepare) in the research of preparation of preparation, have been surprisingly found that, when by the D of Eliquis A crystal formations90(90% particle volume has less than finger
Determine the diameter of diameter D) at 40-85 μm, obtained Eliquis preparation dissolution rate change is very small, and dissolution rate is almost for control
Do not changed by the change of particle diameter, obtained the homogeneous Eliquis preparation of dissolution.
The particle diameter of defined refers to the particle diameter determined using laser scattering technology, D in the present invention90It refer to 90% granule
Product has the diameter less than designated diameter D, such as D90There is the diameter less than 85 μm for 85 μm of particle volumes of expression 90%.
The present invention provides a kind of Apixaban tablet, contains Eliquis raw material and pharmaceutic adjuvant, wherein Eliquis raw material
The X-ray powder diffraction represented with 2 θ angles at 12.8 ± 0.2 °, 13.9 ± 0.2 °, 17.0 ± 0.2 °, 18.4 ± 0.2 °,
22.2 ± 0.2 °, there is characteristic peak at 26.9 ± 0.2 °, the particle diameter D of the Eliquis raw material for being used90It is 40-85 μm.
The X-ray powder diffraction that described Eliquis raw material is represented with 2 θ angles at 12.8 ± 0.2 °, 13.9 ±
0.2 °, 17.0 ± 0.2 °, 18.4 ± 0.2 °, 18.8 ± 0.2 °, 21.1 ± 0.2 °, 21.5 ± 0.2 °, 22.2 ± 0.2 °, 24.7 ±
0.2 °, 26.9 ± 0.2 °, there is characteristic peak at 29.9 ± 0.2 °.
In above-mentioned Apixaban tablet, the amount of Eliquis raw material is 2.5mg or 5mg.
Described pharmaceutic adjuvant includes filler, disintegrant, lubricant and surfactant.
Described filler is selected from lactose, mannitol, microcrystalline cellulose, fructose, sorbierite, sucrose, starch or its combination.
Described disintegrant is selected from Ac-Di-Sol, PVPP, Sodium Hydroxymethyl Stalcs, low substitution hydroxyl
Third cellulose, pregelatinized starch or its combination.
Described lubricant is selected from magnesium stearate, superfine silica gel powder, talcum powder, hydrogenated vegetable oil, polyethylene glycols, dodecane
Base sodium sulphate, Stepanol MG or its combination.
Described surfactant is selected from lauryl sodium sulfate, Stepanol MG or its combination.
Preferably, described filler is lactose and microcrystalline cellulose, and disintegrant is Ac-Di-Sol, lubrication
Agent is magnesium stearate, and surfactant is lauryl sodium sulfate, and the percentage by weight of each component is as follows：Eliquis 2.5%,
Lactis Anhydrous 45.0-47.5%, microcrystalline cellulose 45.0-47.5%, Ac-Di-Sol 3%-5%, magnesium stearate
0.8%-1.2%, lauryl sodium sulfate 0.9%-1.1%.
In above-mentioned Apixaban tablet, the percentage by weight of each component is more preferably：Eliquis 2.5%, anhydrous lactitol
Sugar 46.25%, microcrystalline cellulose 46.25%, Ac-Di-Sol 3%, magnesium stearate 1.0%, dodecyl sulphate
Sodium 1.0%.
Brief description of the drawings
Fig. 1：The X-ray powder diffraction spectrogram of Eliquis A crystal formations；
Fig. 2：Different D90Eliquis preparation it is molten in the 0.1N hydrochloric acid solutions containing 0.05% lauryl sodium sulfate
Go out curve ratio compared with
Fig. 3：Different D90Eliquis preparation in the pH4.5 acetate buffers containing 0.05% lauryl sodium sulfate
Stripping curve compare
Fig. 4：Different D90Eliquis preparation in the pH6.8 phosphate buffers containing 0.05% lauryl sodium sulfate
Stripping curve compare
Fig. 5：Different D90Stripping curve of the Eliquis preparation in the water containing 0.05% lauryl sodium sulfate compare
Fig. 6：Different D90Eliquis preparation in the pH6.8 phosphate buffers containing 0.05% lauryl sodium sulfate
Stripping curve compare (5mg Eliquis)
Specific embodiment
Eliquis A crystal formations are used in comparative example 1-4 as described below, embodiment 1-6.
Comparative example 1
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 21 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Comparative example 2
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 29 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Embodiment 1
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 40 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Embodiment 2
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 52 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Embodiment 3
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 74 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Embodiment 4
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 85 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Comparative example 3
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 90 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
Comparative example 4
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 103 μm.
(2) crushing of recipe quantity auxiliary material is taken, is sieved for subsequent use.
(3) by recipe quantity Eliquis, microcrystalline cellulose, Lactis Anhydrous, Ac-Di-Sol, dodecyl sulphur
Sour sodium is added after being well mixed in mixer, adds magnesium stearate (interior to add) to be well mixed, and granulation obtains hybrid particles；
(4) magnesium stearate (additional) is well mixed together with the hybrid particles obtained by step (3) in mixer；
(5) by the granulation obtained by step (4)；
(6) it is coated, coating weight gain 2%-4%.
The dissolution rate of test case 1 is detected
Detection method is respectively with 0.1N hydrochloric acid solution, pH4.5 vinegar of the 900ml containing 0.05% lauryl sodium sulfate (SLS)
Phthalate buffer, water and pH6.8 phosphate buffers are dissolution medium.Using Chinese Pharmacopoeia four 0,931 second methods of version in 2015
Paddle method.Rotating speed is 50rpm, is measured by sampling respectively at 5,10,15,30,45,60min.
It is appropriate that reference substance solution takes Eliquis reference substance, accurately weighed, is dissolved with methyl alcohol and diluted and is made standard inventory
Solution, then the solution being made in every 1ml containing about Eliquis 0.005mg is diluted with dissolution medium, shake up, it is molten as reference substance
Liquid.
Testing result is as shown in the table, and Dissolution profiles figure is shown in accompanying drawing 2,3,4,5.
Table 1
Table 2
Table 3
Table 4
There is notable difference in the stripping curve that can be seen that comparative example 1 and 2 respectively by accompanying drawing 2-5, comparative example 3 and right
The stripping curve of ratio 4 there is also notable difference, and not have notable difference between the stripping curve of embodiment 1-4.This explanation is worked as
The granularity D of Eliquis90During less than 40 μm or more than 85 μm, granularity change can cause dissolution homogeneity to be deteriorated.And Eliquis
Granularity D90When changing in 40 μm~85 μ ms, dissolution homogeneity will not be caused to be deteriorated.
Dissolution rate testing result according to table 1- tables 4 is also found that in four kinds of different dissolution mediums, when Ah piperazine is husky
The granularity D of class90During less than 40 μm (comparative example 1,2), comparative example 1 and comparative example 2 were in 5 minutes and 10 minutes RSD values of dissolution rate
Respectively more than 15% and 10%.As the granularity D of Eliquis90During more than 85 μm when (comparative example 3,4), its dissolution rate was at 15 minutes
And the RSD values of follow-up individual time point are more than 10%, homogeneity is deteriorated.And work as Eliquis granularity D90For 40-85 μm when, its
Dissolution rate RSD is preferably and smaller with the change of particle diameter.
In sum, the present invention is found surprisingly that, as granularity D90During less than 40 μm, granularity change can cause stripping curve
Significant change, also, within this range, the RSD values of 5 minutes and 10 clock dissolution rates more than 10% (difference between piece and piece compared with
Greatly)；As granularity D90During more than 85 μm, granularity change can also cause the significant change of stripping curve, also, within this range, 15
The RSD values of the dissolution rate of minute and follow-up individual time point are more than 10% (difference between piece and piece becomes big)；Work as Eliquis
Granularity D90For 40-85 μm when, granularity change will not cause the change of stripping curve, and Each point in time dissolution rate in the range of this
RSD be respectively less than 10% (difference between piece and piece is small).
Embodiment 5
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 52 μm.
(2) by recipe quantity Eliquis, microcrystalline cellulose, mannitol, Ac-Di-Sol, dodecyl sulphate
Magnesium and superfine silica gel powder are added in mixer and are well mixed；
(3) compressing tablet；
(4) it is coated, coating weight gain 2%-4%.
Embodiment 6
Preparation process：
(1) recipe quantity Eliquis are taken, is pulverized and sieved, and measure its D90It is 85 μm.
(2) mannitol crushing, sieving, other auxiliary material sieving for standby are taken；
(3) by recipe quantity Eliquis, microcrystalline cellulose, mannitol, PVPP (interior to add), dodecyl sulphate
Magnesium, superfine silica gel powder (interior to add) are added in mixer and are well mixed, and are well mixed, and add wetting agent to pelletize, and are dried, and obtain particle；
(4) step (3) gained particle, PVPP (additional), superfine silica gel powder (additional) are added to mixer together
In be well mixed；
(5) compressing tablet；
(6) it is coated, coating weight gain 2%-4%.
The dissolution rate of test case 2 is detected
Detection method is situated between by dissolution of pH6.8 phosphate buffers of the 900ml containing 0.05% lauryl sodium sulfate (SLS)
Matter.Using Chinese Pharmacopoeia four 0,931 second method paddle method of version in 2015.Rotating speed is 50rpm, respectively at 5,10,15,30,45,
60min is measured by sampling.
It is appropriate that reference substance solution takes Eliquis reference substance, accurately weighed, is dissolved with methyl alcohol and diluted and is made standard inventory
Solution, then the solution being made in every 1ml containing about Eliquis 0.005mg is diluted with dissolution medium, shake up, it is molten as reference substance
Liquid.
As shown in table 5, Dissolution profiles figure is shown in accompanying drawing 6 to testing result.
The preferred embodiment of the present invention described in detail above.But, the present invention is not limited in above-mentioned implementation method
Detail, in range of the technology design of the invention, various simple variants can be carried out to technical scheme.This
A little simple variants belong to protection scope of the present invention.
It is further to note that each particular technique feature described in above-mentioned specific embodiment, in not lance
In the case of shield, can be combined by any mode.In order to avoid unnecessary repetition, the present invention is to various possible groups
Conjunction mode is no longer separately illustrated.
Additionally, can also be combined between a variety of implementation methods of the invention, without departing from this hair
Bright thought, it should equally be considered as content disclosed in this invention.
Claims (10)
1. a kind of Apixaban tablet, contains Eliquis raw material and pharmaceutic adjuvant, it is characterised in that described Eliquis raw material
The X-ray powder diffraction represented with 2 θ angles at 12.8 ± 0.2 °, 13.9 ± 0.2 °, 17.0 ± 0.2 °, 18.4 ± 0.2 °,
22.2 ± 0.2 °, there is characteristic peak at 26.9 ± 0.2 °, the particle diameter D of the Eliquis raw material for being used90It is 40-85 μm.
2. Apixaban tablet according to claim 1, it is characterised in that described Eliquis raw material is represented with 2 θ angles
X-ray powder diffraction in 12.8 ± 0.2 °, 13.9 ± 0.2 °, 17.0 ± 0.2 °, 18.4 ± 0.2 °, 18.8 ± 0.2 °, 21.1
± 0.2 °, 21.5 ± 0.2 °, 22.2 ± 0.2 °, 24.7 ± 0.2 °, 26.9 ± 0.2 °, there is characteristic peak at 29.9 ± 0.2 °.
3. the Apixaban tablet according to claim 1-2, it is characterised in that the amount of Eliquis raw material be 2.5mg or
5mg。
4. Apixaban tablet according to claim 3, it is characterised in that described pharmaceutic adjuvant includes filler, disintegration
Agent, lubricant and surfactant.
5. Apixaban tablet according to claim 4, it is characterised in that described filler is selected from lactose, mannitol, micro-
Crystalline cellulose, fructose, sorbierite, sucrose, starch or its combination.
6. Apixaban tablet according to claim 4, it is characterised in that described disintegrant is fine selected from cross-linked carboxymethyl
The plain sodium of dimension, PVPP, Sodium Hydroxymethyl Stalcs, low-substituted hydroxypropyl cellulose, pregelatinized starch or its combination.
7. Apixaban tablet according to claim 4, it is characterised in that described lubricant is selected from magnesium stearate, micro mist
Silica gel, talcum powder, hydrogenated vegetable oil, polyethylene glycols, lauryl sodium sulfate, Stepanol MG or its combination.
8. Apixaban tablet according to claim 4, it is characterised in that described surfactant is selected from dodecyl sulphur
Sour sodium, Stepanol MG or its combination.
9. Apixaban tablet according to claim 4, it is characterised in that described filler is lactose and microcrystalline cellulose
Element, disintegrant is Ac-Di-Sol, and lubricant is magnesium stearate, and surfactant is lauryl sodium sulfate, respectively
The percentage by weight of component is as follows：Eliquis 2.5%, Lactis Anhydrous 45.0-47.5%, microcrystalline cellulose 45.0-47.5% are handed over
Connection sodium carboxymethylcellulose 3%-5%, magnesium stearate 0.8%-1.2%, lauryl sodium sulfate 0.9%-1.1%.
10. Apixaban tablet according to claim 9, it is characterised in that the percentage by weight of each component is as follows：Ah piperazine is husky
Class 2.5%, Lactis Anhydrous 46.25%, microcrystalline cellulose 46.25%, Ac-Di-Sol 3%, magnesium stearate 1.0%, 12
Sodium alkyl sulfate 1.0%.
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| CN109528674A (en) * | 2018-12-20 | 2019-03-29 | 南京海辰药业股份有限公司 | A kind of Eliquis pharmaceutical composition and preparation method thereof containing hydrophilic version |
| CN112791057A (en) * | 2021-02-07 | 2021-05-14 | 齐飞 | Slow release preparation containing edoxaban and preparation method thereof |
| WO2024016993A1 (en) * | 2022-07-21 | 2024-01-25 | 扬子江药业集团上海海尼药业有限公司 | Apixaban tablet and method for preparing same |
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