CN107536831A - A kind of composition and preparation method containing vildagliptin and melbine - Google Patents
A kind of composition and preparation method containing vildagliptin and melbine Download PDFInfo
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- CN107536831A CN107536831A CN201610505488.2A CN201610505488A CN107536831A CN 107536831 A CN107536831 A CN 107536831A CN 201610505488 A CN201610505488 A CN 201610505488A CN 107536831 A CN107536831 A CN 107536831A
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Abstract
The invention provides a kind of preparation method of the composition containing vildagliptin and melbine, including：S1) adhesive of 1~10 parts by weight is dissolved in water and/or alcoholic solvent, obtains granulation liquid；S2 the melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt) are subjected to fluidization granulation and drying with the granulation liquid, then the vildagliptin of 1~5 parts by weight of addition and/or its pharmaceutically acceptable salt and the mix lubricant of 1~5 parts by weight are uniform, tabletting, obtain the composition containing vildagliptin and melbine.Compared with prior art, the present invention using fluidization granulation simplifies production process, while fluidization granulation improves material flow, and the particle for making to obtain is more loose adds compressibility；Further, since vildagliptin and its pharmaceutically acceptable salt are not added in pelletization, so that its process contaminants reduce.
Description
Technical field
The invention belongs to technical field of medicine, more particularly to it is a kind of containing vildagliptin and melbine
Composition and preparation method thereof.
Background technology
Vildagliptin is that a kind of have selective, competitive, reversible DPP-4 inhibitor.Vildagliptin leads to
Cross and combine to form DPP-4 compounds with DPP-4 and suppress the activity of the enzyme, improving GLP-l concentration, promoting
While B cell produces insulin, Glucagon concentrations are reduced, so as to reduce blood glucose, and to body
Have no significant effect again.And the classical antidiabetic drug melbine of vildagliptin melbine Compound Tablet set and new
The advantage of type dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin, can cooperate with rise GLP-1 levels with
And regulation islet cell function, lose weight, contribute to the effective Blood sugar management of patient safety.
Novartis of Yuan Yan producers label includes hydroxypropyl cellulose, magnesium stearate, vildagliptin, melbine.
Coating membrane contains：Hydroxypropyl methylcellulose, polyethylene glycol, talcum powder, titanium dioxide, iron oxide yellow.
Water is avoided as far as possible because vildagliptin is to moisture-sensitive, therefore in preparation process, and in tablet
Moisture is also required to be stored in reduced levels, if moisture is higher in tablet, medicine easily drops
Solution.Yuan Yan producers use a kind of special preparation technique, i.e., it is double to obtain diformazan using hot-melt extrusion process
Guanidine particle.Product is ground in above-mentioned original, due to using special installation, causes production process to be responsible for, if
Melbine and vildagliptin mixing wet granulation, then because technical process touches moisture, then about thing
Matter increases；If the independent dry granulation of melbine, the compressibility of melbine can not be improved, if
Add filler such as microcrystalline cellulose and improve its compressibility, then because the moisture such as microcrystalline cellulose are higher, and
It is difficult to remove when drying, then impurity increases comparatively fast during shelf-stability.
The content of the invention
In view of this, the technical problem to be solved in the present invention is to provide one kind containing vildagliptin and diformazan pair
Composition of guanidine and preparation method thereof, the preparation method is simple and the composition compressibility of preparation is preferable.
The invention provides a kind of preparation method of the composition containing vildagliptin and melbine, including：
S1) adhesive of 1~10 parts by weight is dissolved in water and/or alcoholic solvent, obtains granulation liquid；
S2) melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are entered with the granulation liquid
Row fluidization granulation and drying, then add the vildagliptin of 1~5 parts by weight and/or its is pharmaceutically acceptable
Salt and the mix lubricant of 1~5 parts by weight are uniform, tabletting, obtain the group containing vildagliptin and melbine
Compound.
Preferably, the ratio of the water and/or alcoholic solvent and adhesive is (10~50) ml：1g.
Preferably, described adhesive is selected from hydroxypropyl methylcellulose and/or hydroxypropylcellulose.
Preferably, the lubricant is in magnesium stearate, hard fumaric acid sodium and glyceryl tristearate
One or more.
Preferably, the step S2) be specially：
The melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are carried out being put into fluid bed to enter
Row preheated fluidification, then spray the granulation liquid granulation simultaneously while dry, then add 1~5 parts by weight
Vildagliptin and/or its pharmaceutically acceptable salt and the mix lubricant of 1~5 parts by weight are uniform, tabletting,
Obtain the composition containing vildagliptin and melbine.
Preferably, the step S2) be specially：
The melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are carried out being put into fluid bed to enter
Row preheated fluidification, then spray the granulation liquid granulation simultaneously while dry, then add 1~5 parts by weight
Vildagliptin and/or its pharmaceutically acceptable salt are well mixed, and finally add the lubrication of 1~5 parts by weight
Agent is well mixed, tabletting, obtains the composition containing vildagliptin and melbine.
Preferably, described adhesive is 2~5 parts by weight.
Preferably, the melbine and/or its pharmaceutically acceptable salt are 10~80 parts by weight.
Preferably, the vildagliptin is 1~5 parts by weight.
Present invention also offers a kind of composition containing vildagliptin and melbine.
The invention provides a kind of preparation method of the composition containing vildagliptin and melbine, including：
S1) adhesive of 1~10 parts by weight is dissolved in water and/or alcoholic solvent, obtains granulation liquid；S2) by 5~95
The melbine of parts by weight and/or its pharmaceutically acceptable salt carry out fluidization granulation with the granulation liquid and done
It is dry, then add the vildagliptin and/or its pharmaceutically acceptable salt and 1~5 parts by weight of 1~5 parts by weight
Mix lubricant it is uniform, tabletting, obtain the composition containing vildagliptin and melbine.With existing skill
Art is compared, and the present invention simplifies production process using fluidization granulation, while fluidization granulation improves raw material stream
Dynamic property, and the particle for making to obtain is more loose adds compressibility；Further, since do not have in pelletization
Have and add vildagliptin and its pharmaceutically acceptable salt, so that its process contaminants reduce.
Embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that and described embodiment is only part of the embodiment of the present invention, rather than all
Embodiment.Based on the embodiment in the present invention, those of ordinary skill in the art are not making creativeness
The every other embodiment obtained under the premise of work, belongs to the scope of protection of the invention.
The invention provides a kind of preparation method of the composition containing vildagliptin and melbine, including：
S1) adhesive of 1~10 parts by weight is dissolved in water and/or alcoholic solvent, obtains granulation liquid；S2) by 5~95
The melbine of parts by weight and/or its pharmaceutically acceptable salt carry out fluidization granulation with the granulation liquid and done
It is dry, then add the vildagliptin and/or its pharmaceutically acceptable salt and 1~5 parts by weight of 1~5 parts by weight
Mix lubricant it is uniform, tabletting, obtain the composition containing vildagliptin and melbine.
Wherein, the present invention is not particularly limited to the source of all raw materials, is commercially available.
In the present invention, the content of described adhesive is preferably 2~10 parts by weight, more preferably 2~8 parts by weight,
It is further preferably 2~5 parts by weight；Described adhesive is adhesive well known to those skilled in the art, and
It is preferably hydroxypropyl methylcellulose and/or hydroxypropylcellulose in the present invention without special limitation；The present invention is in group
The filler such as cellulose family and adhesive PVP class of the easy moisture absorption are not added in compound, therefore can be made
Water tariff collection in composition makes relevant material to maintain relatively low level in relatively low level.
Adhesive is first dissolved in water and/or alcoholic solvent by the present invention, obtains granulation liquid；Preferably, first will be viscous
Mixture is dissolved in water or alcohol solution；The ratio of the water and/or alcoholic solvent and adhesive is preferably
(10~100) ml：1g, more preferably (10~50) ml：1g, it is further preferably (10~30) ml：1
G, most preferably 15ml：1g.
The melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are carried out with the granulation liquid
Vulcanization is granulated and dried；The content of the melbine and/or its pharmaceutically acceptable salt is preferably
10~80 parts by weight, more there are preferably 20~80 parts by weight, be further preferably 40~80 parts by weight, be most preferably
60~80 parts by weight；In the present invention, the step is preferably specially：By melbine and/or its pharmaceutically
Acceptable salt carries out fluidisation preheating, then sprays the granulation liquid granulation and while dries；The fluidisation
The temperature of preheating is preferably 55 DEG C~70 DEG C；The temperature of the drying is preferably 55 DEG C~60 DEG C.
After drying, the vildagliptin and/or its pharmaceutically acceptable salt and 1~5 weight of 1~5 parts by weight are added
The mix lubricant for measuring part is uniform；Wherein, the vildagliptin and/or its pharmaceutically acceptable salt contain
Amount is preferably 1~5 parts by weight；The vildagliptin pharmaceutically acceptable salt is that those skilled in the art are ripe
Its pharmaceutically acceptable salt known, has no special limitation, is preferably sulfuric acid dimension lattice in the present invention
Arrange spit of fland, phosphoric acid vildagliptin, hydrochloric acid vildagliptin and the one or more in fumaric acid vildagliptin；Institute
The content for stating lubricant is preferably 1~3 parts by weight；The lubricant is profit well known to those skilled in the art
Lubrication prescription, special limitation is had no, be preferably magnesium stearate, hard fumaric acid sodium and three in the present invention
One or more in tristerin.
In the present invention, it is preferred to after drying, vildagliptin and/or pharmaceutically acceptable salt mixing are first added
After uniformly, it is uniform to add mix lubricant.
After well mixed, tabletting, preferably also it is coated, obtains the group containing vildagliptin and melbine
Compound.The method of the tabletting and coating is method well known to those skilled in the art, and it is special to have no
Limitation.
Such as by melbine and vildagliptin mixing wet granulation, due to touching moisture in technical process,
So that relevant material in composition can be made to increase, as melbine uses drying and granulating, then can not improve
The compressibility of melbine, such as by the independent wet granulation of melbine, but it is for example micro- to be such as added without filler class
If crystalline cellulose, the poor compressibility of particle can be caused, it can cause moisture if adding microcrystalline cellulose
It is higher, and be difficult to remove when drying, impurity can increase comparatively fast during shelf-stability.Therefore,
The present invention simplifies production process using fluidization granulation, while fluidization granulation improves material flow, and
And the particle for making to obtain is more loose adds compressibility；Further, since dimension is not added in pelletization
Ge Lieting and its pharmaceutically acceptable salt, so that its process contaminants reduce.
Contain vildagliptin and combination with metformin by prepared by above-mentioned preparation method present invention also offers a kind of
Thing.
In order to further illustrate the present invention, Wei Gelie is contained to one kind provided by the invention with reference to embodiments
Composition of spit of fland and melbine and preparation method thereof is described in detail.
Reagent used is commercially available in following examples；Agents useful for same source is as follows in embodiment：
Eucreas commercially available products:Novartis；
Vildagliptin：Jiangsu is permanent to contain；
Metformin hydrochloride：Shandong Ke Yuan；
Hard magnesium：The Anhui mountains and rivers；
Opadry：Ka Lekang.
Embodiment 1
1.1 by 20g hydroxypropyl celluloses, are dissolved in 300mL purification of aqueous solutions and are prepared into granulation liquid.
1.2 by melbine 400g, is put into fluid bed fluidisation, and stream temperature is 65 DEG C, obtains suspending mixed
Compound material.
1.3 will pelletize on suspended mixture material that the granulation liquid in 1.1 is sprayed in 1.2,60 DEG C of dryings,
Additional vildagliptin 20g is well mixed, and stiffened fatty acid magnesium is well mixed, tabletting, prepares Opadry coating
Liquid is simultaneously coated, and obtains vildagliptin diformin tablet.
Embodiment 2
2.1 by 20g hydroxypropyl celluloses, are dissolved in 300mL purification of aqueous solutions and are prepared into granulation liquid.
2.2 by melbine 500g, is put into fluid bed fluidisation, and stream temperature is 65 DEG C, obtains suspending mixed
Compound material.
The granulation liquid is sprayed on the suspended mixture material and pelletized by 2.3,60 DEG C of dryings, additional dimension lattice
Row spit of fland 25g is well mixed, and stiffened fatty acid magnesium is well mixed, tabletting, is prepared Opadry coating solution and is carried out
Coating, obtains vildagliptin diformin tablet.
Comparative example 1：Wet granulation
1.1 will be prepared into granulation liquid in 100mL purification of aqueous solutions.
1.2 is double by microcrystalline cellulose 520g, sodium carboxymethylcellulose 57.5g, PVP 20g, diformazan
Guanidine 1000g is put into high-speed granulator and is well mixed, and obtains suspended mixture material.
Wetting agent is sprayed on suspended mixture material and pelletized by 1.3, and the wet granular after granulation passes through 0.1mm
The rocking type granule-finishing machine in aperture, the particle after whole grain are dried in fluid bed, 60 DEG C of EAT when drying,
It is 1~2% to dry to pellet moisture, then is added into hopper mixer, adds raw material vildagliptin 50
G is well mixed, then additional magnesium stearate lubricant 20g, mixes 3min, 10rpm, rotary pelleting machine
Tabletting, hardness are 180~220N.
1.4 prepare Opadry coating solutions, the product obtained in 1.3 are coated using coating pan, coating weight gain
For 1~2%, vildagliptin diformin tablet is obtained.
Comparative example 2：Wet granulation
2.1 will be prepared into granulation liquid in 100mL purification of aqueous solutions,
2.2 by sodium carboxymethylcellulose 57.5g, and PVP 20g, melbine 1000g are put at a high speed
It is well mixed in granulator, obtains suspended mixture material.
Granulation liquid is sprayed on suspended mixture material and pelletized by 2.3, and the wet granular after granulation passes through 0.1mm holes
The rocking type granule-finishing machine in footpath, the particle after whole grain are dried in fluid bed, 60 DEG C of EAT when drying, done
Dry to pellet moisture is 1~2%, then adds in hopper mixer, it is equal to add raw material vildagliptin 50g mixing
It is even, then additional magnesium stearate lubricant 20g, mix 3min, 10rpm, rotary pelleting machine tabletting, firmly
Spend for 80~120N.
2.4 prepare Opadry coating solutions, and the product obtained in 2.3 is coated using coating pan, is coated
Increase weight as 1~2%, obtain vildagliptin diformin tablet.
To the vildagliptin melbine obtained in embodiment 1, embodiment 2, comparative example 1 and comparative example 2
The performance of piece is detected, and obtains the results are shown in Table 1.
The vildagliptin diformin tablet tabletting result of the test of table 1
| Sample | Compressibility | Particle bulk density | Tap density |
| Embodiment 1 | 260N | 0.40g/mL | 0.63g/mL |
| Embodiment 2 | 240N | 0.52g/mL | 0.68g/mL |
| Comparative example 1 | 220N | 0.56g/mL | 0.71g/mL |
| Comparative example 2 | 80N | 0.62g/mL | 0.78g/mL |
From the above it can be seen that the particle compressibility that the improved fluidized bed granulation technique of inventor obtains
Have 260N, embodiment 2 has 240N, and if be added without microcrystalline cellulose with traditional wet granulation can
Pressure property only has 80N, is unsatisfactory for tabletting conditions, 220N is can reach after addition, but due to being added in prescription
Microcrystalline cellulose, on the one hand cause piece weight larger, thus prove the melbine via fluidized bed granulation
Compressibility is relatively preferable, and without piece weight is significantly increased；Compressibility is with particle bulk density and jolt ramming simultaneously
The increase of density, and reduce.
Stability test
Experiment be by《Chinese Pharmacopoeia》2000 editions two annex XIXC medicine stability test guidelines
Design.
Detection project：Loss on drying, relevant material, content.
Detection method：Relevant substance detecting method is HPLC methods in stability, and the method is relevant for checking
Material (maximum single miscellaneous and total miscellaneous).
Accelerated test：The Wei Ge obtained in Example 1, embodiment 2, comparative example 1 and comparative example 2
Spit of fland melbine sample is arranged, is put into relative humidity 75%, temperature is that 6 are placed in 40 DEG C of climatic chambers
Month, in 1,2,3,6 month sampling detection indices, it the results are shown in Table 2.
40 DEG C of 2 vildagliptin melbine of table, 75%RH accelerated test results
Conclusion：By result above it can be seen that, the sample shelf-stability mistake of different embodiments and comparative example
Loss on drying has no significant change in journey, but due to adding microcrystalline cellulose in comparative example, so water
Divide of a relatively high；After different embodiment shelf-stability processes reality is can be seen that from the variation tendency of impurity
Apply example 1 and impurity in embodiment 2 is relatively low, and the extension impurity increase of impurity over time is more slow；
, may be relevant with moisture etc. and 0 day relevant material impurities in comparative example are higher, used in prescription
Excipient also accelerates conversion rate, at the same during shelf-stability the increased speed of impurity also compared with it
His prescription is fast, while impurity 7, and embodiment is also smaller compared with comparative example prescription.
The measure of release in vitro and internal blood concentration
Release in vitro：Each 6 of the sample and Eucreas commercially available products obtained in Example 1, use is molten
Out-degree determination method II methods：Slurry processes (50rpm) carry out dissolution rate detection, and medium is 900mL pH0.1M
Hydrochloric acid solution, dissolution rate is measured by sampling 5,10,15,30,45,60min respectively, obtains result and sees
Table 3.
The dissolution data of 3 different samples of table
The vildagliptin melbine sample obtained as can be seen from the above using the preparation technology of the present invention is released
Put very fast, and the sample of comparative example 2 is consistent with listing sample, relatively slow, and each time difference compared with
Greatly, release in 60 minutes only reaches 80% or so, and preparation method provided by the invention just reaches in 30min
90%.
Internal medicine moves：Rat 24 is taken, is randomly divided into 2 groups, every group each 12, gavage is given respectively
By embodiment 1 and listing product, then taken a blood sample upon administration respectively at 0.5,1,2,4,8 hour, body
Outer anticoagulant heparin, with 2000rmin-1Centrifuge blood plasma, Cord blood.
Blood plasma is taken into centrifuge tube, acetonitrile precipitation albumen is added, is centrifuged after vortex mixed, supernatant is used
After methanol solvate, sample introduction, blood concentration is determined with HPLC, obtains the results are shown in Table 4.
Animal data in the rat body of 4 different samples of table
As can be seen from the above results, the vildagliptin diformin tablet obtained in embodiment 1 is in rat body
Relative listing reference substance (4h) Wei Ge that is shorter, and being obtained in embodiment 1 of interior peak time (2h)
The commercially available product that relatively listed up to Cmax for arranging spit of fland diformin tablet wants height, i.e., the vildagliptin two that prepared by the present invention
The release of first biguanides piece is more abundant, the effect of being advantageous to improve patient.Further demonstrate improvement of the present invention
Lifting of the technique to product quality.
Claims (10)
- A kind of 1. preparation method of the composition containing vildagliptin and melbine, it is characterised in that including：S1) adhesive of 1~10 parts by weight is dissolved in water and/or alcoholic solvent, obtains granulation liquid；S2) melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are entered with the granulation liquid Row fluidization granulation and drying, then add the vildagliptin of 1~5 parts by weight and/or its is pharmaceutically acceptable Salt and the mix lubricant of 1~5 parts by weight are uniform, tabletting, obtain the group containing vildagliptin and melbine Compound.
- 2. preparation method according to claim 1, it is characterised in that the water and/or alcoholic solvent with The ratio of adhesive is (10~50) ml：1g.
- 3. preparation method according to claim 1, it is characterised in that described adhesive is selected from hydroxypropyl Methylcellulose and/or hydroxypropylcellulose.
- 4. preparation method according to claim 1, it is characterised in that the lubricant is selected from tristearin Sour magnesium, hard fumaric acid sodium and the one or more in glyceryl tristearate.
- 5. preparation method according to claim 1, it is characterised in that the step S2) be specially：The melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are carried out being put into fluid bed to enter Row preheated fluidification, then spray the granulation liquid granulation simultaneously while dry, then add 1~5 parts by weight Vildagliptin and/or its pharmaceutically acceptable salt and the mix lubricant of 1~5 parts by weight are uniform, tabletting, Obtain the composition containing vildagliptin and melbine.
- 6. preparation method according to claim 1, it is characterised in that the step S2) be specially：The melbine of 5~95 parts by weight and/or its pharmaceutically acceptable salt are carried out being put into fluid bed to enter Row preheated fluidification, then spray the granulation liquid granulation simultaneously while dry, then add 1~5 parts by weight Vildagliptin and/or its pharmaceutically acceptable salt are well mixed, and finally add the lubrication of 1~5 parts by weight Agent is well mixed, tabletting, obtains the composition containing vildagliptin and melbine.
- 7. preparation method according to claim 1, it is characterised in that described adhesive is 2~5 weights Measure part.
- 8. preparation method according to claim 1, it is characterised in that the melbine and/or its Pharmaceutically acceptable salt is 10~80 parts by weight.
- 9. preparation method according to claim 1, it is characterised in that the vildagliptin is 1~5 Parts by weight.
- A kind of 10. composition containing vildagliptin and melbine prepared by any one of claim 1~9.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019182756A (en) * | 2018-04-03 | 2019-10-24 | 大原薬品工業株式会社 | Solid preparation containing vildagliptin |
| CN114886862A (en) * | 2022-05-17 | 2022-08-12 | 北京悦康科创医药科技股份有限公司 | Compound hypoglycemic medicine preparation and its preparing method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103845326A (en) * | 2014-03-24 | 2014-06-11 | 江苏奥赛康药业股份有限公司 | Compound composition of vildagliptin and melbine and preparation method thereof |
| CN105125539A (en) * | 2015-08-05 | 2015-12-09 | 浙江华海药业股份有限公司 | Pioglitazone metformin tablet and preparation method thereof |
| CN105582008A (en) * | 2014-11-14 | 2016-05-18 | 北京赛林泰医药技术有限公司 | Composition containing vildagliptin and metformin and preparation method of composition |
-
2016
- 2016-06-29 CN CN201610505488.2A patent/CN107536831A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103845326A (en) * | 2014-03-24 | 2014-06-11 | 江苏奥赛康药业股份有限公司 | Compound composition of vildagliptin and melbine and preparation method thereof |
| CN105582008A (en) * | 2014-11-14 | 2016-05-18 | 北京赛林泰医药技术有限公司 | Composition containing vildagliptin and metformin and preparation method of composition |
| CN105125539A (en) * | 2015-08-05 | 2015-12-09 | 浙江华海药业股份有限公司 | Pioglitazone metformin tablet and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019182756A (en) * | 2018-04-03 | 2019-10-24 | 大原薬品工業株式会社 | Solid preparation containing vildagliptin |
| CN114886862A (en) * | 2022-05-17 | 2022-08-12 | 北京悦康科创医药科技股份有限公司 | Compound hypoglycemic medicine preparation and its preparing method |
| CN114886862B (en) * | 2022-05-17 | 2024-02-02 | 北京悦康科创医药科技股份有限公司 | Compound hypoglycemic medicine preparation and its preparing process |
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Application publication date: 20180105 |