CN106727368A - A kind of Dapagliflozin pharmaceutical composition and preparation method thereof - Google Patents
A kind of Dapagliflozin pharmaceutical composition and preparation method thereof Download PDFInfo
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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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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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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Abstract
The present invention provides a kind of Dapagliflozin pharmaceutical composition, it is characterised in that described pharmaceutical composition is by following weight percents into being grouped into：Dapagliflozin microcrystalline cellulose compositions 1%~95%, filler/adhesive 0%~95%, disintegrant 0%~20%, lubricant 0.1%~5%, glidant 0%~10%.The present invention uses microcrystalline cellulose as carrier material, the inventive method mixes Dapagliflozin with microcrystalline cellulose, heating melts Dapagliflozin, and Dapagliflozin is covered in microcrystalline cellulose surface in liquid form, and medicine is set in microcrystalline cellulose surface after cooling, form the compound of Dapagliflozin and microcrystalline cellulose, increased the specific surface area of Dapagliflozin, therefore the dissolution rate of medicine, steady quality can be increased, preparation method of the present invention is simple and easy to apply, is adapted to industrialized production.
Description
Technical field
The present invention relates to medicine preparation, and in particular to a kind of sodium-glucose sugar cotransporter 2
The preparation method of inhibitor Dapagliflozin composition.
Background technology
Diabetes are a kind of common endocrine metabolism diseases, be characterized in hyperglycaemia with because
Sugared, the fatty and protein metabolism that hypoinsulinism and/or effect defect cause is disorderly.
Counted according to IDF (IDF), global diabetic's quantity (20 years old in 2014
To 79 years old) reach 3.87 hundred million people, it is contemplated that it was up to 5.92 hundred million people in 2035.And II type
Diabetes be the most common form of diabetes, its account in diabetes cases 90%.Its high-frequency
Complication, such as diabetes, kidney failure etc. not only has influence on the quality of life of patient, and
And it is likely to result in the shortening in life-span.Due to patients with NIDDM can not be appropriate in response to pancreas
Island element, and insulin is to receive endogenous or exogenous material such as by the beta Cell of islet in pancreas
The stimulation of glucose, lactose, ribose, arginine, hyperglycemic factor etc. and the hatching egg secreted
White matter hormone.Blood sugar can be generally converted into energy or blood sugar is stored in cell by insulin
Used after being provided with.For patients with NIDDM, its body produces normal amount even higher amount pancreas
During the element of island, but because the effect of some mechanism prevents insulin from glucose sugar is transferred in cell,
Cause the glucose in blood to raise, hyperglycemia state is presented, and lasting hyperglycemia is led
Glucose toxicity is caused, is made insulin resistance more serious and is facilitated Pancreatic beta cells function to hinder
Hinder, ringing has aggravated the control of type II diabetes.
SLGT-2 inhibitor (sodium-glucose sugar inhibitor of cotransporter 2,
The inhibitors of sodium-glucose co-transporter 2) it is that one kind being capable of specificity
Suppress glomerulus proximal tubule, to filtration glucose reabsorption, make excessive glucose from urine
Middle discharge, directly reduces the medicine of blood sugar.The SLGT-2 inhibitor class medicines for clinically using
There are Dapagliflozin (Dapagliflozin, trade nameAstraZenca&
Bristol-Myers Squib companies), canagliflozin (Canagliflozin,
Johnson＆Johnson companies), En Gelie net (Empagliflozin, trade nameBoehringer Ingelheim＆Eli Lilly companies), in addition also
There is compound medicine：Compound medicine (the trade name of canagliflozin and melbine),
Compound medicine (the trade name of Dapagliflozin and melbine), En Gelie is net/profit
Compound medicine (the trade name of Ge Lieting) etc..
Dapagliflozin is a kind of SGLT-2 inhibitor, beautiful during by Boehringer Ingelheim company and hundred
Shi Guibao companies are researched and developed jointly, and FDA approval listings are obtained in January, 2014.Its chemical name
For：The chloro- 5- of 2- (Β-D- glucopyranose -1- bases) -4'- ethoxy diphenyl first
Alkane；(1S) -1,5- is dehydrated -1-C- [the chloro- 3- of 4- [(4- ethoxyl phenenyls) methyl] phenyl]-D- Portugals
Grape sugar alcohol.Its structural formula is：
Dapagliflozin indissoluble in the aqueous solution of pH1-8, to meet clinical application requirement, it is necessary to
Increase its dissolubility in an aqueous medium.Patent CN20080044077 discloses Dapagliflozin
With the preparation method of melbine drug combination preparation, improved by reducing the method for particle diameter
Solubility.Patent CN 200880016902 discloses the preparation method of Dapagliflozin piece, passes through
Dapagliflozin and propane diols monohydrate are made into the method for eutectic to improve dissolubility, however it is molten
Although solution degree increases, dissolution velocity is very slow, it is still necessary to reduce grain by fine method
Footpath.
Research finds that Dapagliflozin fusing point is low (75~80 DEG C), if its standard machinery is micronized
It is easily tacky to reduce particle diameter, need to be crushed using low-temperature airflow, operation high to equipment requirement
It is cumbersome, low production efficiency.Other Dapagliflozin material density is small, if size controlling is in smaller model
Enclose, such as D90≤ 50 μm, easily float, dust is big, can not even if being made propylene glycol hydrate
Improve, contact area is greatly increased, it is necessary to special protection and environment dust Control, increase production
Potential safety hazard.Follow-up to attempt using 4%-8% hydroxypropylcellulose aqueous solution wet granulations, mixing is not
It is even, and granulation heat production for a long time, cause drug accumulation, particle diameter to increase, influence dissolution.Therefore,
It is necessary to improve its preparation method, solubility can be improved, and beneficial to industrialized production.
The content of the invention
The technical problems to be solved by the invention are to overcome above-mentioned weak point, research and design energy
Solubility is improved, beneficial to the Dapagliflozin pharmaceutical composition and preparation method thereof of industrialized production.
The invention provides a kind of Dapagliflozin pharmaceutical composition, matched by following weight percent
Into being grouped into：
Dapagliflozin microcrystalline cellulose compositions 1%~95%, filler/adhesive 0%~95%, collapse
Solution agent 0%~20%, lubricant 0.1%~5%, glidant 0%~10%.
Preferably, a kind of Dapagliflozin pharmaceutical composition of the invention, is matched by following weight percent
Into being grouped into：
Dapagliflozin microcrystalline cellulose compositions 10%~85%, filler or adhesive 10%~75%,
Disintegrant 0.25%~10%, lubricant 0.2%~2%, glidant 1%~4%.
In Dapagliflozin microcrystalline cellulose compositions of the present invention, Dapagliflozin and microcrystalline cellulose
The weight ratio of element is 1:2 to 1:20, preferably 1:8 to 1:15.
Microcrystalline cellulose of the present invention is selected fromThe PH101 of type, PH102,
PH301, PH302 or silicified microcrystalline cellulose.
Filler of the present invention is selected from microcrystalline cellulose or lignose；Or selected from lactose, sugarcane
Sugar, fructose, starch, pregelatinized starch, cornstarch, modified corn starch, glucose,
Mannitol, xylitol, sorbierite, inorganic salts (such as calcium carbonate, calcium phosphate, Dicalcium Phosphate,
Calcium sulfate), two or more mixtures in dextrin or maltodextrin.Being preferably filled with agent is
Microcrystalline cellulose and/or lactose.
Lactose of the present invention be selected from Lactis Anhydrous, lactose monohydrate, fast flo lactose, directly
Pressure lactose or modified lactose.
Adhesive of the present invention be selected from hydroxypropyl cellulose, cornstarch, pregelatinized starch,
Two kinds in modified starch, polyvinylpyrrolidone, HPMC or ethyl cellulose
Or various mixtures.Preferred adhesive is pregelatinized starch.
Disintegrant of the present invention is selected from Ac-Di-Sol, crosslinked polyethylene pyrrolidines
Ketone, starch, pregelatinized starch, cornstarch, microcrystalline cellulose or low substituted hydroxy-propyl fiber
Element, preferred disintegrant is PVPP.
Lubricant of the present invention be selected from magnesium stearate, talcum powder, Brazil wax, palm wax,
Palmitic acid, stearic acid, sodium stearyl fumarate, neopelex or hydrogenated vegetable oil,
The lubricant of preferred feedstock particle is magnesium stearate.
Glidant of the present invention is selected from silica, colloidal silica, magnesium silicate, three silicon
Sour magnesium, talcum or silica, preferred glidant are silica.
Tablet of the invention optionally carries out film coating.
Coating membrane generally weightening is 2%~5%.Coating powder is commercially available.
It is a further object of the present invention to provide the preparation side of the Dapagliflozin pharmaceutical composition
Method, the method comprises the following steps：
(1) Dapagliflozin and microcrystalline cellulose are mixed in high shear mixing granulator, is obtained
Dapagliflozin microcrystalline cellulose mixt；
(2) said mixture is heated to 70~200 DEG C by selection baking oven or heating mantle, makes melting,
Cooled down after being stirred with high shear mixing granulator or band screw rod hot-melt extruded machine, lattice row must be reached
Net Microcrystalline cellulose composite；
(3) after Dapagliflozin Microcrystalline cellulose composite is well mixed with pharmaceutic adjuvant, it is made
Dapagliflozin pharmaceutical composition.
Step described in the inventive method (2) heat melting process in, due to Dapagliflozin
Fusing point is 75~80 DEG C, and the carburizing temperature of microcrystalline cellulose is more than 260 DEG C.Selection baking oven or
Heating mantle or the high shear mixing granulator with heating covering device or band screw rod hot-melt extruded machine
It is prepared, heating-up temperature is 70~200 DEG C, more preferably preferably 75~150 DEG C, 80~90 DEG C.
The present invention prepare Dapagliflozin microcrystalline cellulose mobility preferably, therefore can with it is herein
Excipient needed for described one or more fills glue after being mixed together with any order for needing
Capsule or compressing tablet.Wet granulation, dry granulation process or known in the art any can also be used
It is prepared by other pharmaceutically acceptable methods.
Effect of the invention：
(1) present invention uses microcrystalline cellulose as carrier material, and microcrystalline cellulose is a kind of
Pure native cellulose depolymerization product, white, odorless, tasteless is water insoluble, does not have fiber
Property and mobility is extremely strong, due to the special nature such as low degree and large specific surface area,
Its own can act also as diluent, there is certain lubrication and calving disaggregation, be adapted at subsequent technique
Reason, is also not in need to control larger piece without rolling up disintegrant consumption in prescription
The problem of weight.
(2) present invention has screened the ratio of Dapagliflozin and microcrystalline cellulose, and crystallite is worked as in discovery
When cellulose ratios increase, the composition tablet dissolution rate of formation increases therewith.Be probably due to
Microcrystalline cellulose ratio increases, Dapagliflozin in the Dapagliflozin Microcrystalline cellulose composite of formation
Degree of grinding improve, caused by the increase of the specific surface area of Dapagliflozin.
(3) the inventive method mixes Dapagliflozin with microcrystalline cellulose, and heating makes Da Gelie
Net melting, under agitation, Dapagliflozin is merged into each other with microcrystalline cellulose, Dapagliflozin
Microcrystalline cellulose surface is covered in liquid form, and medicine is set in microcrystalline cellulose table after cooling
Face, forms the compound of Dapagliflozin and microcrystalline cellulose.Can selectively enter as needed
Row pulverising step, obtains suitable particle diameter, carries out follow-up preparation process treatment.According to the technique,
Because Dapagliflozin is to be covered in microcrystalline cellulose surface after melting, equivalent to increased Da Gelie
Net specific surface area, therefore the dissolution rate of medicine can be increased.
(4) compared with the inventive method prepares solid dispersions with hot-melt extruded method：
Hot-melt extruded method prepares solid dispersions and uses polymer carrier, general to have viscosity,
Such as PVP, HPC, HPMC etc..In preparation process, medicine melts, and polymer carrier
In melten glass state, medicine is cooled down after being merged with macromolecular material, forms solid dispersions.One
As to ensure syncretizing effect, the ratio of polymer carrier and medicine reaches more than 2 times, right
, it is necessary to polymer carrier at least more than 20mg, Gao Han for this product 10mg specifications
The adhesive carrier of amount act as the effect of adhesive, have one for the treatment of follow-up preparation process
Fixed difficulty, for example, mainly need to add substantial amounts of disintegrant, while bringing moisture-sensitive, influences
Stability etc. various problems.
This method prepares Dapagliflozin microcrystalline cellulose compositions after hot melt granulation, cools down, meeting
More open particulate matter is formed, can easily be sieved and be obtained final product Dapagliflozin microcrystalline cellulose group
Compound, without special crushing operation.If batch is smaller, 30 mesh, 40 mesh sieve hands may be selected
Dynamic sieving, if batch is larger, can use the pelletizing machine whole grain in 1.0mm or 1.2mm apertures.So
Method obtained in mobility of particle preferably, facilitate subsequent technique to process.
The preparation method that the present invention is provided is melted medicine, therefore the Da Gelie for feeding intake
Net particle without strict demand, it is relatively easy for preparation process, without to Dapagliflozin
Mechanical crushing or air-flow crushing are carried out, cost and production time has been saved.
Pharmaceutical preparation prepared by the present invention can be packaged in and ensure any of pharmaceutical preparation stability
In packaging.For example, high density polyethylene (HDPE) (HDPE) air-tight bottle or lining equipped with silica-gel desiccant
There is the aluminium bubble-cap of polyvinyl chloride (PVC).
Dapagliflozin microcrystalline cellulose compositions need heating to melt in preparation process, therefore right
Do not limited too much in the particle diameter of the Dapagliflozin for feeding intake, crushed without low-temperature airflow, this point
It has been greatly reduced raw material process equipment requirement and cost.
The Dapagliflozin microcrystalline cellulose compositions steady quality that the present invention is provided, further prepares
Tablet, capsule there is the In Vitro Dissolution behavior equivalent with airflow pulverization method, and preparation side
Method is simple and easy to apply, is adapted to industrialized production.
Brief description of the drawings
The stripping curve figure of Fig. 1 embodiments 5~10
It is the stripping curve figure of embodiment 5
It is the stripping curve figure of embodiment 6
It is the stripping curve figure of embodiment 7
It is the stripping curve figure of embodiment 8
It is the stripping curve figure of embodiment 9
It is the stripping curve figure of embodiment 10
Specific embodiment
With reference to embodiment, the invention will be further described.These embodiments illustrate for
Implement the best mode being currently contemplated of the invention, it is intended that illustrate rather than the limitation present invention.
To prove advantages of the present invention,
Following examples raw material and pharmaceutic adjuvant are commercially available.
The particle diameter of the Dapagliflozin raw material used by embodiment 1~4 is D90=110 μm.
(particle diameter D90 means that " the cumulative particle size distribution number of a sample reaches 90% when institute
90%) corresponding particle diameter ", i.e. particle diameter account for less than its particle
Embodiment 5~8 is obtained Dapagliflozin cellulose composition in embodiment 1~4
Grain.
The particle diameter of the Dapagliflozin raw material that embodiment 9 is used is D90=33 μm, is by air-flow
Breaking method crushes (D90=110 μm) acquisition of commercially available product.Airslide disintegrating mill model：AO is (preferably
Emerging pure and fresh powder machinery company), operating condition：Pump pressure 0.4MPa.
D90=110 μm of the particle diameter of the Dapagliflozin raw material used by embodiment 10.It is commercially available product.
Embodiment 1：The preparation of Dapagliflozin cellulose combination composition granule：
10g Dapagliflozins and 40g microcrystalline celluloses are weighed, after mixing in addition hot-melt extruded machine,
Temperature is set to 70 DEG C, after extrusion, takes out cooling, is crushed using mechanical crusher, will crush
Material afterwards crosses 30 mesh sieves, obtains Dapagliflozin cellulose combination composition granule 40g.
Embodiment 2：The preparation of Dapagliflozin cellulose combination composition granule：
10g Dapagliflozins and 70g microcrystalline celluloses are weighed, band heating covering device is added after mixing
High shear mixing granulator in granulated, temperature is set to 75 DEG C, after stirring 10min,
Cooling is taken out, is crushed using mechanical crusher, the material after crushing is crossed into 40 mesh sieves, obtained
Dapagliflozin cellulose combination composition granule 70g.
Embodiment 3：The preparation of Dapagliflozin cellulose combination composition granule：
10g Dapagliflozins and 100g microcrystalline celluloses are weighed, after mixing 10min, constant temperature is added
In case, temperature is set to 80 DEG C, after placing 20min, cooling is taken out, using mechanical crusher
Crush, the material after crushing is crossed into 50 mesh sieves, obtain Dapagliflozin cellulose combination composition granule
100g。
Embodiment 4：The preparation of Dapagliflozin cellulose combination composition granule：
10g Dapagliflozins and 130g microcrystalline celluloses are weighed, hot-melt extruded machine is added after mixing
In, temperature is set to 85 DEG C, after extrusion, takes out cooling, is made using the rotation of aperture 1.0mm
Grain machine carries out whole grain, obtains Dapagliflozin cellulose combination composition granule 130g.
Embodiment 5-10：The preparation of Dapagliflozin piece or capsule,
The grain of Dapagliflozin cellulose composition and Dapagliflozin raw material in Example 1~4
Footpath is particle diameter the reaching for D90=33 μm (2) of D90=110 μm (1), Dapagliflozin raw material
Lattice arrange net raw material, and piece agent 1000 or capsule 1000 are prepared according to the formula of following table.
Tablet and capsule particulate composition
Q.s. refer to be enough to constitute granulating composition with Dapagliflozin and adjust formula for 100%w/w
Amount.
The unit of following each raw materials：g
Preparation method (1000)：Dapagliflozin particle is weighed by formula ratio and other auxiliary materials (are removed
Magnesium stearate), mix 5~10min, magnesium stearate is added afterwards, mix 2~5min, compressing tablet is adjusted
Nodal plate weight and hardness, it is 40~80N to control hardness.Tablet press machine model：STC-ZPS8 (Shanghai day
Auspicious pharmaceutical machine Co., Ltd).
Tablet is coated：It is formulated conventionally and is coated fluid solid content 20.0%.Coating pan model：BY-300 is (safe
State city Tian Tai pharmaceutical machines factory).Coating conditions：Rotating speed 12rpm, atomizing pressure 0.3MPa,
60 DEG C of EAT.It is coated rear panel weight 250mg
It is prepared by capsule：Directly filled after weighing Dapagliflozin particle and the mixing of other auxiliary materials by formula ratio
It is encapsulated.Capsule machine model：Automated capsule filling machine(IN-Cap).
Stripping curve is determined：Dapagliflozin piece in above-described embodiment 5~10 is taken, each 6, is adopted
With《Chinese Pharmacopoeia》(version two in 2010) annex XC dissolution methods are determined in accordance with the law：
Dissolving device, slurry processes；Rotating speed, 50rpm；Temperature：37±0.5℃；Dissolution is controlled：Acetic acid
Salt buffer (pH4.5)；Medium volume：1000ml；Analysis method：High performance liquid chromatography
(HPLC)；Detection wavelength：220nm；Mobile phase：Water-acetonitrile (60:40)；Flow velocity：1ml/min；
Chromatographic column：Agilent Zorbax SB-C18 posts (5 μm, 4.6*220mm)；Column temperature：25℃；
Sampling volume：20μl.
Dissolution the results are shown in Table 4.
The Dapagliflozin tablet dissolution result % of table 4.
Result shows：Embodiment 5~9 is compared with Example 10, it can be seen that bulk drug is passed through
After crossing treatment, dissolution rate is obviously improved.
Embodiment 5~8 compared with Example 9 compared with, it can be seen that using being prepared into microcrystalline cellulose
The tablet dissolution rate of the bulk drug of promotor composition is with use through the raw material medicine phases after air-flow crushing
Than, dissolution rate quite or faster.
Claims (10)
1. a kind of Dapagliflozin pharmaceutical composition, it is characterised in that described pharmaceutical composition by
Following weight percent proportioning into being grouped into：
Dapagliflozin microcrystalline cellulose compositions 1%~95%, filler/adhesive 0%~95%, collapse
Solution agent 0%~20%, lubricant 0.1%~5%, glidant 0%~10%.
2. a kind of Dapagliflozin pharmaceutical composition, it is characterised in that described pharmaceutical composition by
Following weight percent proportioning into being grouped into：
Dapagliflozin microcrystalline cellulose compositions 10%~85%, filler or adhesive 10%~75%,
Disintegrant 0.25%~10%, lubricant 0.2%~2%, glidant 1%~4%.
3. Dapagliflozin pharmaceutical composition according to claim 1 and 2, its feature exists
In, in the Dapagliflozin microcrystalline cellulose compositions, the weight of Dapagliflozin and microcrystalline cellulose
Amount is than being 1:2 to 1:20, preferably 1:8 to 1:15.
4. Dapagliflozin pharmaceutical composition according to claim 3, it is characterised in that
The microcrystalline cellulose is selected fromPH101, PH102, PH301, PH302 of type
Or silicified microcrystalline cellulose.
5. Dapagliflozin pharmaceutical composition according to claim 1 and 2, its feature exists
In the filler is selected from microcrystalline cellulose or lignose；Or selected from lactose, sucrose, fruit
Sugar, starch, pregelatinized starch, cornstarch, modified corn starch, glucose, mannitol,
Xylitol, sorbierite, inorganic salts：Calcium carbonate, calcium phosphate, Dicalcium Phosphate, calcium sulfate,
Two or more mixtures in dextrin or maltodextrin；Agent is preferably filled with for microcrystalline cellulose
And/or lactose.
6. Dapagliflozin pharmaceutical composition according to claim 5, it is characterised in that
The lactose is selected from Lactis Anhydrous, and lactose monohydrate, fast flo lactose or changes vertical compression lactose
Property lactose.
7. Dapagliflozin pharmaceutical composition according to claim 1 and 2, its feature exists
In described adhesive is selected from hydroxypropyl cellulose, cornstarch, pregelatinized starch, modified shallow lake
Two or more in powder, polyvinylpyrrolidone, HPMC or ethyl cellulose
Mixture, preferred adhesive is pregelatinized starch.
8. Dapagliflozin pharmaceutical composition according to claim 1 and 2, its feature exists
In the disintegrant is selected from Ac-Di-Sol, PVPP, shallow lake
Powder, pregelatinized starch, cornstarch, microcrystalline cellulose or low-substituted hydroxypropyl cellulose, it is excellent
The disintegrant of choosing is PVPP.
9. Dapagliflozin pharmaceutical composition according to claim 1 and 2, its feature exists
In the lubricant is selected from magnesium stearate, talcum powder, Brazil wax, palm wax, palm
Acid, stearic acid, sodium stearyl fumarate, neopelex or hydrogenated vegetable oil, it is excellent
The lubricant of choosing is magnesium stearate；The glidant be selected from silica, colloidal silica,
Magnesium silicate, magnesium trisilicate, talcum or silica, preferred glidant are silica.
10. the preparation method of Dapagliflozin pharmaceutical composition as claimed in claim 1 or 2,
Characterized in that, the method comprises the following steps：
(1) Dapagliflozin and microcrystalline cellulose are mixed in high shear mixing granulator, is obtained
Dapagliflozin microcrystalline cellulose mixt；
(2) said mixture is heated to 70~200 DEG C by selection baking oven or heating mantle, makes melting,
Cooled down after being stirred with high shear mixing granulator or band screw rod hot-melt extruded machine, lattice row must be reached
Net Microcrystalline cellulose composite；
(3) after Dapagliflozin Microcrystalline cellulose composite is well mixed with pharmaceutic adjuvant, it is made
Dapagliflozin pharmaceutical composition；
In melting process is heated, selection baking oven or heating mantle or band are heated the step (2)
The high shear mixing granulator or band screw rod hot-melt extruded machine of covering device are prepared, heating temperature
It is 70~200 DEG C to spend, preferably 75~150 DEG C, more preferably 80~90 DEG C.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111374968A (en) * | 2018-12-27 | 2020-07-07 | 山东鲁抗医药股份有限公司 | Composition containing dapagliflozin and preparation method and application thereof |
| CN111481522A (en) * | 2020-04-07 | 2020-08-04 | 乐普制药科技有限公司 | Dapagliflozin microencapsulated sustained-release tablet and preparation method thereof |
| CN111956622A (en) * | 2020-09-15 | 2020-11-20 | 北京福元医药股份有限公司 | Dagliflozin propylene glycol hydrate pharmaceutical preparation |
| CN114028356A (en) * | 2021-12-28 | 2022-02-11 | 浙江海翔药业股份有限公司 | Dapagliflozin tablet and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015011113A1 (en) * | 2013-07-22 | 2015-01-29 | Sandoz Ag | Formulations containing amorphous dapagliflozin |
| CN104586803A (en) * | 2015-02-12 | 2015-05-06 | 浙江华海药业股份有限公司 | Preparation method of empagliflozin microcrystalline cellulose composition |
| CN104586795A (en) * | 2014-12-30 | 2015-05-06 | 山东博迈康药物研究有限公司 | Invokana tablet and preparation method thereof |
| WO2015104658A2 (en) * | 2014-01-08 | 2015-07-16 | Dr. Reddy’S Laboratories Limited | Amorphous solid dispersion of dapagliflozin and process for the preparation of amorphous dapagliflozin |
| WO2015128853A1 (en) * | 2014-02-28 | 2015-09-03 | Sun Pharmaceutical Industries Limited | Dapagliflozin compositions |
| CN105496966A (en) * | 2015-12-18 | 2016-04-20 | 北京华禧联合科技发展有限公司 | Medicine composition for Jardiance solid dispersion and preparation method thereof |
-
2015
- 2015-11-24 CN CN201510822343.0A patent/CN106727368A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015011113A1 (en) * | 2013-07-22 | 2015-01-29 | Sandoz Ag | Formulations containing amorphous dapagliflozin |
| WO2015104658A2 (en) * | 2014-01-08 | 2015-07-16 | Dr. Reddy’S Laboratories Limited | Amorphous solid dispersion of dapagliflozin and process for the preparation of amorphous dapagliflozin |
| WO2015128853A1 (en) * | 2014-02-28 | 2015-09-03 | Sun Pharmaceutical Industries Limited | Dapagliflozin compositions |
| CN104586795A (en) * | 2014-12-30 | 2015-05-06 | 山东博迈康药物研究有限公司 | Invokana tablet and preparation method thereof |
| CN104586803A (en) * | 2015-02-12 | 2015-05-06 | 浙江华海药业股份有限公司 | Preparation method of empagliflozin microcrystalline cellulose composition |
| CN105496966A (en) * | 2015-12-18 | 2016-04-20 | 北京华禧联合科技发展有限公司 | Medicine composition for Jardiance solid dispersion and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 罗明生等: "《药剂辅料大全 第2版》", 31 January 2006, 成都：四川出版集团.四川科学技术出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111374968A (en) * | 2018-12-27 | 2020-07-07 | 山东鲁抗医药股份有限公司 | Composition containing dapagliflozin and preparation method and application thereof |
| CN111481522A (en) * | 2020-04-07 | 2020-08-04 | 乐普制药科技有限公司 | Dapagliflozin microencapsulated sustained-release tablet and preparation method thereof |
| CN111956622A (en) * | 2020-09-15 | 2020-11-20 | 北京福元医药股份有限公司 | Dagliflozin propylene glycol hydrate pharmaceutical preparation |
| CN111956622B (en) * | 2020-09-15 | 2022-11-15 | 北京福元医药股份有限公司 | Dapagliflozin propylene glycol hydrate pharmaceutical preparation |
| CN114028356A (en) * | 2021-12-28 | 2022-02-11 | 浙江海翔药业股份有限公司 | Dapagliflozin tablet and preparation method thereof |
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