CN106580962A - Compound metformin and vildagliptin tablet and preparation method thereof - Google Patents
Compound metformin and vildagliptin tablet and preparation method thereof Download PDFInfo
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- CN106580962A CN106580962A CN201611271866.1A CN201611271866A CN106580962A CN 106580962 A CN106580962 A CN 106580962A CN 201611271866 A CN201611271866 A CN 201611271866A CN 106580962 A CN106580962 A CN 106580962A
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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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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Abstract
The invention discloses a compound metformin and vildagliptin tablet and a preparation method thereof. The metformin and the vildagliptin serve as active ingredients of the drug and are combined with a pharmaceutical adjuvant adhesive to form particles, a lubricating agent is added to prepare the tablet, the adhesive is one or more of polyvinylpyrrolidones K30, K45, K60, K70 and K80, and the dosage of the adhesive is 5%-20% of the weight of the composition. The particles can be prepared by adopting a one-step granulation and a one-step granulation and dry-process granulation combined mode. The dissolution property and stability of the preparation are improved while liquidity and compressibility of the particles are improved, and the tablet has good in-vivo bioavailability and a clinical curative effect.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of answering containing melbine and vildagliptin
Square piece agent and preparation method thereof.
Background technology
Diabetes are one group of metabolic diseases being characterized with hyperglycaemia.Hyperglycaemia be then due to defect of insulin secretion or
Its biological agent is damaged, or both have concurrently and cause.The state of chronic hyperglycemia of diabetes is significantly correlated with long-term complications, i.e., many
The infringement of multiple organ, dysfunction and MSOF, particularly kidney, eye, nerve, heart and blood vessel etc..The synthesis of diabetes
Treatment, should not only be conceived to makes blood sugar be down to close normal level, and should actively correct metabolic disorder and reduce the heart
Vascular risk factors.
It is at present that the symptom for having diabetes according to WHO/ADA standards adds casual plasma grape to the definition of diabetes
Sugar level >=11.1mmol/L, or fasting plasma glucose level >=7.0mmol/L, or in oral glucose tolerance test,
Plasma glucose levels >=the 11.1mmol/L of 2-h after 75g anhydrous grape glucose loads.If lacking typical diabetic symptom, no
Only diabetes can be diagnosed with a blood sugar detection, it is necessary to the next day it is confirmed after diagnose again.
According to Pathologic Characteristics, diabetes can be divided into type i diabetes and type ii diabetes.Type ii diabetes are one group and send out
The complicated metabolic disorder that interpretation of the cause, onset and process of an illness system is only partly known.It includes different degrees of islet beta cell function reduction, surrounding tissue pancreas islet
Element opposing and hepatic glycogen metabolic disorder.The glycemic control of type ii diabetes As time goes on, in progressive deteriorate become
Gesture；It is average to need to use a kind of new hypoglycemic medicine therapeutic intervention hand per 3-4 after diet control and kinesiatrics fail
Section, to reach or maintain good glycemic control.Finally, even if in current Cocktail treatment and/or insulin therapy feelings
Under condition, still there is quite a few patient to be unable to reach good glycemic control.Overweight, hypertension and hyperlipidemia often with sugar
Urine disease merges and exists, be to the therapeutic intervention of multiple cardiovascular risk factors in diabetes complex treatment it is considerable it is important because
Element.
Diabetes have become the third-largest disease of the serious harm human health after cardiovascular, malignant tumour.One
" national Diabetes Epidemiological Investigation (2007-2008) " shows, in China crowd of more than 20 years old, the sugar of masculinity and femininity
Respectively up to 10.6% and 8.8%, overall diabetes prevalence is 9.7% to the sick illness rate of urine, thus, extrapolates national diabetes total
Number of patients is about 92,000,000 people, alreadys exceed India, becomes the most country of diabetic in the world.
At present, every, U.S. diabetic year medical expense up to 11744 dollars, be ND more than 2 times.
In past 5 years, government is that the expense that diabetic pays increased 32%, up to 174,000,000,000 dollars.Wherein, 116,000,000,000 is beautiful
Unit is used for the medical expense related to diabetes, 58,000,000,000 dollars be treat, delay work due to patient, the indirect loss such as premature death.
Only in one area of Hawaii, America, the annual expenditure for diabetic is just up to 1,000,000,000 dollars.If can not find early, arrive
Treated again when diabetic complication occurs, the effect of diet and motion can be very limited, it is necessary to medication.If kidney work(
Energy exhaustion needs dialysis, and annual medical expense is not lower 100,000 yuan.China is used for the expenditure of diabetes for 2002 and accounts for health
4% for going out, 188.2 hundred million yuan altogether.General diabetes 3726 yuan of average cost for each person every year, once there is complication, average flower
Take up to 13897 yuan
Melbine is the hypoglycemic medicine of biguanides, is the widely used oral antihyperglycemic agent thing of current countries in the world man, can
Improve tolerance of the type ii diabetes patient to sugar, reduce basis and Post-prandial plasma glucose concentration.Metformin hydrochloride does not promote
Enter insulin secretion, its blood sugar reducing function predominantly promotes adipose tissue ingestion of glucose, increase musculature anerobic glycolysis, increase
Plus the utilization of glucose, moreover it is possible to reduce the gastral absorptions of glucose Jing.
Vildagliptin is that one kind has selective, competitive, reversible DPP IV (DPP-IV) inhibitor, also
Claim incretin reinforcing agent, by the degradation speed for suppressing the activity of DPP-IV to reduce pancreas hyperglycaemia sample peptide I GLP-1,
And then stimulate the secretion of insulin under high blood glucose concentration, and can discharge, promote by postponing gastric emptying, glucagon suppression
Enter the approach such as beta Cell of islet propagation and differentiation and enhancing satietion to play anti-type ii diabetes function.And to body weight without bright
Development rings.
EMEA ratifies the Metformin hydrochloride/vildagliptin Compound Tablet listing of Novartis, trade name in November, 2007：(preferably with auspicious).Treatment type ii diabetes, still can not effectively be controlled for treatment using melbine maximum tolerated dose
The patient of blood sugar processed or the current patient that vildagliptin (Galvus) and melbine has been used in combination.The specification of the composite tablet
For Metformin hydrochloride/vildagliptin 500mg/50mg, 850mg/50mg, 1000mg/50mg.
Because the dosage of melbine accounts for more than 80%, the dosage of vildagliptin is less than 10%, and melbine mobility
It is very poor, there is mixing problem of non-uniform.The compressibility extreme difference of melbine, and dosage is big, and rolling process is for poor compressibility
Material is unacceptable, therefore is unfavorable for dry granulation.Meanwhile, vildagliptin is a kind of poor compressibility and with hygroscopicity
Material, to water sensitive, meeting water can be susceptible to degraded for it.In order to overcome this problem, there is patent to vildagliptin using straight
Connecing the mode of compressing tablet carries out the preparation of tablet, and it possesses good every property, but the general drug load of direct tablet compressing is less than
20%, the active ingredient of indication of the present invention reaches more than 90%, and active ingredient poor fluidity, it is impossible to using the side of direct tablet compressing
It is prepared by method.If pelletized using normal wet, moisture and high temperature are difficult to avoid that, obvious shadow is produced to the stability of vildagliptin
Ring.Find in implementation process：(1) dry granulation is adopted, mobility of particle is poor, piece outward appearance and tablet weight variation are unqualified；(2) adopt
Tablet prepared by the wet granulation technology relevant material in stability study increases too fast, medicine it is off quality.
CN103845326A discloses a kind of compound containing melbine and vildagliptin and preparation method thereof,
Comprising：(1) vildagliptin or its officinal salt；(2) melbine or its officinal salt；(3) adhesive；Described adhesive be
The apparent viscosity of 1% aqueous solution is 2～4mpas hydroxypropyl celluloses or Hydroxypropyl methylcellulose, and its consumption is composition weight
20～30%.It discloses composite tablet of a kind of melbine and vildagliptin and preparation method thereof：(1) by first by two
Adhesive (by dry weight in terms of) of the first biguanides with 20～30% is pelletized with organic solvent, is then mixed with vildagliptin and other auxiliary materials
Preparation compressing tablet afterwards；(2) melbine, adhesive are dissolved in organic solvent, revolving is obtained after solid according to granulation, Ran Houyu
Preparation compressing tablet after vildagliptin and other auxiliary material mixing；(3) by the lubricant of melbine, adhesive and 50% recipe quantity, do
Preparation compressing tablet after adding vildagliptin to mix with other auxiliary materials after method granulation.This application proposes three kinds of method of granulating, concrete real
Find during applying：(1) normal wet is pelletized for the stability of vildagliptin has an impact, relevant in influence factor process of the test
Material growth rate is fast, for the quality of preparation has a negative impact；Simultaneously dissolution rate is too fast, with comparison medicine dissolved corrosion not
Unanimously, it is difficult to reach good clinical efficacy；(2) dry granulation is due to melbine poor compressibility, mobility of particle after dry method
Substantially reduce with compressibility, prepare because mobility of particle is poor during tablet, tablet appearance and tablet weight variation are unqualified, unfavorable
In the production of tablet.
The content of the invention
The present invention overcomes melbine and vildagliptin composite tablet dissolution is bad, matter according to problem present in technology
Measure the difficult problem such as unstable, it is desirable to provide a kind of melbine and vildagliptin composite tablet composition and preparation method thereof, realize
Preferable stability and more excellent quality.
Invention also provides the preparation method of melbine and vildagliptin composite tablet, the method can be effective
Improve mobility, the compressibility of particle, especially improve vildagliptin and meet after water in stability in normal wet pelletization
During hold problem of easy degradation, so as to ensure vivo biodistribution availability, make clinical to obtain good effect.
Concrete technical scheme of the present invention is as follows：
A kind of composite tablet of melbine and vildagliptin, comprising melbine or its officinal salt, vildagliptin or its can
Pharmaceutical salts and adhesive, described adhesive is one or more in PVP K30, K45, K60, K70, K80,
Its consumption is the 5%～20% of composition weight.
The melbine is 5～30: 1, preferably 5～20: 1 with the consumption mass ratio of vildagliptin.
Aforementioned pharmaceutical compositions, also including lubricant, consumption is the 0.2%～3% of composition weight, further preferably
0.3～1%, one or more in preferred magnesium stearate, talcum powder.
The invention provides a kind of method for preparing the vildagliptin and the composite tablet of melbine, using a step system
Grain method granulation.
Marumerization is also known as boiling granulating method, stream either spray granulation, fluidized bed granulation method：Pass through from bottom to top
In the presence of hot-air, while making material powders keep fluidized state, the solution containing binder is sprayed into, be polymerized to powder knot
The method of particle.It once completes the mixing of conventional wet lay granulation, granulation, dry three steps in closed container.
Concrete preparation process is as follows：
(1) adhesive of melbine, vildagliptin, recipe quantity is pulverized and sieved respectively, is well mixed, with appropriate organic molten
Agent, is pelletized with one-step-granulating method (fluidised bed granulator), is sieved；
Or, the adhesive of melbine, vildagliptin, part recipe quantity is pulverized and sieved respectively, it is well mixed, with appropriate
The adhesive of the remaining recipe quantity of organic solvent dissolving, is pelletized with one-step-granulating method, is sieved；
(2) it is uniform with mix lubricant by pellet through sieves, whole grain obtained in step (1)；
(3) tabletting machine is used.
Or,
(1) adhesive of melbine, vildagliptin, recipe quantity is pulverized and sieved respectively, is well mixed, with appropriate organic molten
Agent, is pelletized with one-step-granulating method (fluidised bed granulator), is sieved；
Or, the adhesive of melbine, vildagliptin, part recipe quantity is pulverized and sieved respectively, it is well mixed, with appropriate
The adhesive of the remaining recipe quantity of organic solvent dissolving, is pelletized with one-step-granulating method, is sieved；
(2) particle obtained in step (1) is pressed into into sheet, sheet is sieved, whole grain；
(3) it is particle obtained in step (2) is uniform with mix lubricant；
(4) tabletting machine is used.
One-step-granulating method of the present invention is this area conventional equipment, be can select such as multifunctional fluidized bed (the wound will of test-type
Electromechanical development in science and technology (Jiangsu) limited company, model：FLZB-1.5, FLZB-3), multipurpose fluid bed (make by Chongqing English lattice
Grain packaging technique Co., Ltd, model：WBF-3G, WBF-5G, WBF-15G) etc..
Organic solvent described in said method is alcohols solvent or its mixed solvent with water, preferably 70%～95% second
Alcoholic solution, the consumption of the organic solvent for composition weight 30%～80% (V/W), more preferably 45%～60%.
The adhesive of the part recipe quantity is the 5%～95% of binder dosage, more preferably 40～70%.
Because the dosage difference of two kinds of active medicines of vildagliptin in compound preparation and melbine is larger, easily cause mixed
Close problem of non-uniform.The method preferably improves the uneven problem of mixing.
Tablet prepared by the present invention is according to the preferably suitable different in nature stamping of piece weight, prepared tablet：
Tablet surface is smooth；
Tablet major diameter hardness is between 100～300N；
The friability of tablet is less than 1.0%；
The thickness of tablet is between 4～9mm；
The selection that the present invention passes through adhesive species and feed postition in prescription, and the improvement of preparation method and preferably, can be with
The obvious compressibility for further improving melbine and vildagliptin powder, the little composite tablet of the differences between batches for preparing,
The friability of tablet is qualified, and technological feasibility is high, compressibility that particle is improved well, the Dissolution behaviours for improving preparation and
Stability.The vildagliptin and melbine composite tablet differences between batches that the present invention is provided is little, and technique favorable reproducibility is more suitable for
Industrialized production.
Specific embodiment
In order to be better understood from the present invention, the present invention is illustrated below by specific case study on implementation, in following enforcement
In case, the various processes not described in detail and method are Conventional wisdoms as known in the art.Should correct understanding be：This
The case study on implementation of invention is made to illustrate the present invention, rather than limitation of the present invention, so in the method for the present invention
Under the premise of to the present invention simple transformation fall within the scope of the present invention.
Embodiment 1
Preparation technology：The melbine of the recipe quantity of table 1, vildagliptin are well mixed with adhesive, with 75% ethanol 500ml mono-
Step granulator granulation, crosses 30 mesh sieves, and 30 mesh sieve whole grains after 60 DEG C of dryings add magnesium stearate to mix, compressing tablet.
Table 1
| Title | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| Metformin hydrochloride | 1000g | 1000g | 1000g | 1000g |
| Vildagliptin | 50g | 50g | 50g | 50g |
| HPC-SSL | 315g | 210g | / | / |
| PVP K45 | / | / | / | 120g |
| PVP K60 | / | / | 100g | / |
| Magnesium stearate | 12g | 12g | 5g | 5g |
Influence factor comparative study：The sample that by more than prepared by different prescriptions carries out accelerated stability June test, as a result such as table 2
It is shown：
The accelerated stability June result of the test of table 2
| Total miscellaneous (%) | Acid amides (%) | Ring amidine (%) | Diketone (%) | |
| Prescription 1 | 4.74 | 2.36 | 1.32 | 0.98 |
| Prescription 2 | 4.21 | 2.22 | 1.09 | 0.77 |
| Prescription 3 | 2.41 | 1.11 | 0.69 | 0.37 |
| Prescription 4 | 2.39 | 1.07 | 0.78 | 0.42 |
| Standard limits | ≤3.5 | ≤2.0 | ≤.0 | ≤1.0 |
Result of the test shows：The tablet prepared as adhesive (prescription of patent CN103845326A) using HPC-SSL is being added
Place 6 months under the conditions of speed, amide impurities, ring amidine impurity and total miscellaneous more than drug standards limit, the close medicine of diketone impurity
Standard limits, drug quality is unqualified.The tablet prepared as adhesive using PVP is placed under acceleration conditions 6 months,
Each impurity and total miscellaneous not less than drug standards limit, drug quality is qualified.
Embodiment 2
With Metformin hydrochloride 1000g, vildagliptin 50g, PVP K45 120g, magnesium stearate 5g as prescription, using different
Preparation technology prepares tablet.
Technique 1：Melbine is well mixed with PVP K45, plus 75% ethanol 80ml wet granulations, excessively 30 mesh sieves, 60 DEG C
30 mesh sieve whole grain after drying, adds vildagliptin to mix with magnesium stearate, compressing tablet.
Technique 2：Melbine, vildagliptin and 60gPVP K45 are well mixed, and with 500ml75% ethanol 60g is dissolved
PVP K45 add magnesium stearate to be well mixed, compressing tablet as adhesive, one-step palletizing after 30 mesh sieve whole grains.
Technique 3：Melbine, vildagliptin and 60gPVP K45 are well mixed, and with 500ml75% ethanol 60g is dissolved
, used as adhesive, one-step palletizing, dry granulation compacting is large stretch of after 30 mesh sieve whole grains, crosses 30 mesh sieve whole grains for PVP K45, adds stearic
Sour magnesium is well mixed, compressing tablet.
Technique 4：Melbine, vildagliptin, PVP K45 are well mixed, and 30 mesh sieves are crossed after dry granulation, add stearic acid
Magnesium is well mixed, compressing tablet.
Table 4
| Technique 1 | Technique 2 | Technique 3 | Technique 4 | |
| Plain piece outward appearance | It is smooth, without piebald | It is smooth, without piebald | It is smooth, without piebald | There is piebald on plain piece surface |
| Tablet weight variation | It is qualified | It is qualified | It is qualified | It is unqualified |
| Friability | It is qualified | It is qualified | It is qualified | It is unqualified |
Influence factor comparative study：By sample prepared by above different process carry out the test of high temperature (60 DEG C) influence factor 30 days and
Accelerated stability June tests, and as a result see the table below：
30 days result of the tests of the high temperature of table 5 (60 DEG C) influence factor
| Total miscellaneous (%) | Acid amides (%) | Ring amidine (%) | Diketone (%) | |
| Technique 1 | 14.87 | 10.59 | 0.38 | 3.90 |
| Technique 2 | 3.08 | 1.80 | 0.24 | 0.82 |
| Technique 3 | 3.13 | 1.86 | 0.30 | 0.76 |
| Technique 4 | 13.78 | 7.47 | 2.86 | 3.45 |
| Standard limits | ≤3.5 | ≤2.0 | ≤1.0 | ≤1.0 |
The accelerated stability test June result of table 6
| Total miscellaneous (%) | Acid amides (%) | Ring amidine (%) | Diketone (%) | |
| Technique 1 | 4.55 | 2.56 | 1.05 | 0.89 |
| Technique 2 | 2.62 | 1.16 | 0.82 | 0.35 |
| Technique 3 | 2.51 | 1.12 | 0.78 | 0.38 |
| Technique 4 | 5.85 | 2.89 | 1.81 | 1.04 |
| Standard limits | ≤3.5 | ≤2.0 | ≤1.0 | ≤1.0 |
Result of the test shows：
(1) using dry granulation (technique 4), because mobility of particle is poor during piece is prepared, plain piece outward appearance and the piece method of double differences
Different and friability unqualified (result is as shown in table 4), is unsatisfactory for the basic demand of general tablet, is unfavorable for industrialization production,
Therefore dry granulation is not suitable for the preparation of tablet of the present invention.
(2) place 30 days under the conditions of 60 DEG C of high temperature, using dry granulation (technique 4) and wet granulation (technique 1) preparation
Tablet it is fast about the material growth rate tablet that substantially prepared by marumerization (technique 2, technique 3) more of the present invention, it is front
The total miscellaneous content of person is about 3 times (result is as shown in table 5) of the latter.
(3) place June under acceleration conditions, the tablet prepared using dry granulation (technique 4) and wet granulation (technique 1)
Stability is poor, acid amides, ring amidine and it is total it is miscellaneous exceed drug standards limit, drug quality is unqualified.According to a step of the present invention
The relevant material of tablet prepared by granulation granulation (technique 2 and technique 3) meets drug standards bound requirements, stablizes with good
Property, drug quality qualified (result is as shown in table 6).
In sum：
(1) melbine is not only relevant with auxiliary material used in prescription with the quality of the composite tablet of vildagliptin, at the same with it is selected
The preparation technology for selecting is even more closely related, selects qualified prescription and technique just to prepare the tablet of high stability.
(2) relevant material is one of critical project in drug quality research, and its content is the straight of reflection medicine purity
Connect index, the bad reaction that medicine is produced in Clinical practice except having outside the Pass with the pharmacologically active of medicine itself, in medicine
The relevant material for existing also has much relations.Tablet according to prescription of the present invention and technique productions is put under acceleration conditions
Put June relevant material and meet drug standards bound requirements, reach the stability requirement of drug quality, drug quality is qualified.
Claims (10)
1. the composite tablet of a kind of melbine and vildagliptin, comprising melbine or its officinal salt, vildagliptin or its
Officinal salt and adhesive, it is characterised in that described adhesive is in PVP K30, K45, K60, K70, K80
One or more, its consumption is the 5%～20% of composition weight.
2. composite tablet as claimed in claim 1, it is characterised in that the mass ratio of melbine and vildagliptin in composition
For 5～30: 1.
3. composite tablet as claimed in claim 1, it is characterised in that also including lubricant, consumption is composition weight
0.2%～3%.
4. pharmaceutical composition as claimed in claim 3, it is characterised in that the lubricant is selected from magnesium stearate and/or talcum
Powder.
5. the preparation method of composite tablet described in any one of Claims 1 to 4, it is characterised in that using marumerization or a step
Mode of the granulation in combination with dry granulation is pelletized.
6. preparation method as claimed in claim 5, it is characterised in that step is as follows：
(1) adhesive of melbine, vildagliptin, recipe quantity is pulverized and sieved respectively, is well mixed, with appropriate organic molten
Agent, is pelletized with one-step-granulating method, is sieved；
Or, the adhesive of melbine, vildagliptin, part recipe quantity is pulverized and sieved respectively, it is well mixed, with appropriate
The adhesive of the remaining recipe quantity of organic solvent dissolving, is pelletized with one-step-granulating method, is sieved；
(2) it is uniform with mix lubricant by pellet through sieves, whole grain obtained in step (1)；
(3) tabletting machine is used.
7. preparation method as claimed in claim 5, it is characterised in that step is as follows：
(1) adhesive of melbine, vildagliptin, recipe quantity is pulverized and sieved respectively, is well mixed, with appropriate organic molten
Agent, is pelletized with one-step-granulating method, is sieved；
Or, the adhesive of melbine, vildagliptin, part recipe quantity is pulverized and sieved respectively, it is well mixed, with appropriate
The adhesive of the remaining recipe quantity of organic solvent dissolving, is pelletized with one-step-granulating method, is sieved；
(2) particle obtained in step (1) is pressed into into sheet, sheet is sieved, whole grain；
(3) it is particle obtained in step (2) is uniform with mix lubricant；
(4) tabletting machine is used.
8. preparation method as claimed in claims 6 or 7, it is characterised in that the organic solvent is alcohols solvent or itself and water
Mixed solvent, the adhesive of the part recipe quantity is the 5%～95% of prescription binder dosage.
9. preparation method as claimed in claim 8, it is characterised in that organic solvent is 70%～95% ethanol solution, described
The consumption of organic solvent is the 30%～80% of composition weight；The adhesive of the part recipe quantity is prescription binder dosage
40～70%.
10. preparation method as claimed in claim 9, it is characterised in that organic solvent is 70%～95% ethanol solution, institute
The consumption for stating organic solvent is the 45%～60% of composition weight.
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| CN201611271866.1A CN106580962B (en) | 2016-12-30 | 2016-12-30 | Metformin and vildagliptin compound tablet and preparation method thereof |
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|---|---|---|---|
| CN201611271866.1A CN106580962B (en) | 2016-12-30 | 2016-12-30 | Metformin and vildagliptin compound tablet and preparation method thereof |
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| CN106580962B CN106580962B (en) | 2020-11-10 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110812337A (en) * | 2018-08-08 | 2020-02-21 | 上海宣泰医药科技有限公司 | Method for preparing aminocaproic acid tablets by fluidized bed granulation method |
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| WO2007078726A2 (en) * | 2005-12-16 | 2007-07-12 | Merck & Co., Inc. | Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with metformin |
| CN101181264A (en) * | 2007-11-27 | 2008-05-21 | 北京润德康医药技术有限公司 | Pharmaceutical composition taking metformin hydrochloride and vigelegting as active component as well as preparing method and uses 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 |
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| CN110812337A (en) * | 2018-08-08 | 2020-02-21 | 上海宣泰医药科技有限公司 | Method for preparing aminocaproic acid tablets by fluidized bed granulation method |
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| CN106580962B (en) | 2020-11-10 |
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