CN106551927A - Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof - Google Patents
Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof Download PDFInfo
- Publication number
- CN106551927A CN106551927A CN201510639366.8A CN201510639366A CN106551927A CN 106551927 A CN106551927 A CN 106551927A CN 201510639366 A CN201510639366 A CN 201510639366A CN 106551927 A CN106551927 A CN 106551927A
- Authority
- CN
- China
- Prior art keywords
- metformin hydrochloride
- vildagliptin
- pharmaceutical composition
- preparation
- carried out
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to technical field of medicine synthesis, discloses a kind of pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof.In the present invention, from certain adjuvant and allocated in specific amount ranges, first metformin hydrochloride is individually pelletized, then the metformin hydrochloride granule of preparation is carried out into mixing granulation with vildagliptin and pharmaceutically acceptable adjuvant again, so as to effectively improve the robustness in tablet manufacture and controllability, favorable reproducibility, produces the tablet of sane, controllable, favorable reproducibility, is adapted to industrialized production.
Description
Technical field
The present invention relates to technical field of medicine synthesis, and in particular to the pharmaceutical composition comprising vildagliptin and metformin hydrochloride and
Its preparation method.
Background technology
Diabetes are a kind of metabolic diseases, are the Portugals caused by the cellular metabolism effect defect due to insufficient insulin or insulin
A kind of syndrome of grape sugar, protein and lipid metabolic disorder.Diabetes can betide any age, as diabetes are fallen ill
The prolongation of time, be easily caused the histopathologies such as nerve, kidney, blood vessel and heart infringement so that finally occur blind, uremia,
Apoplexy and myocardial infarction, or even threat to life.Diabetes are a kind of commonly encountered diseases, and the prevalence of developed country's diabetes is up to
5%-10%, the prevalence of China is up to 3%.
Type 2 diabetes mellitus are also Adult Onset's patients with type Ⅰ DM, more in the sequela of 35-40 year, account for diabeticss more than 90%.2
Patients with type Ⅰ DM produces the ability of insulin in patient body and not completely loses, and in some patient's bodies, insulin is even produced excessively, but
As the Insulin Resistance of body strengthens, and make the action effect of insulin unobvious, therefore the insulin in patient's body lacks
Weary is a kind of relative shortage.
In type 2 diabetes mellitus their early stage client need oral hypoglycemic drug therapy, the antidiabetic medicine that clinic is commonly used at present includes
Sulfonylurea, double flesh classes, thiazolidinedione (glitazone) etc., these medicines have corresponding shortcoming, i.e. muscular tissue without
Oxygen zymolysis increase, and cause lactic acidosiss etc..
Metformin hydrochloride and vildagliptin are two kinds of hypoglycemic medicines, and the mechanism of action of the two is different, can play complementary
Effect.
Metformin hydrochloride does not promote insulin secretion, and its blood sugar reducing function predominantly promotes fatty tissue ingestion of glucose, makes flesh
Meat tissue anerobic glycolysises increase, and increase the utilization of glucose, moreover it is possible to reduce the gastral absorptions of glucose Jing.
Vildagliptin (vildagliptin) is a kind of DPP IV (DPP-IV) inhibitor, also known as incretin reinforcing agent.
The medicine is, by the activity for suppressing DPP-IV, to reduce the degradation speed of glucagon-like peptide (GLP-1), and then in height
Stimulate the secretion of insulin under blood sugar concentration, and can be by postponing gastric emptying, glucagon suppression release, promoting islets of langerhans β
Cell is bred and breaks up and strengthen the approach such as satietion to play anti-type 2 diabetes mellitus function.
The chemical name of vildagliptin is 1- [[(3 monohydroxy, one 1 one adamantyl) amino] acetyl group] one (5)-tetrahydrochysene pyrrole of -2- cyano group
Alkane is coughed up, molecular formula is C17H25N3O2, relative molecular mass is 303.4.Its chemical constitution is as follows:
Chinese patent application CN 101234105A disclose a kind of Pharmaceutical composition containing metformin and vildagliptin and its
Preparation method, vildagliptin, Microcrystalline Cellulose are crossed 80 mesh sieves, mix homogeneously respectively for which, then are progressively increased method and salt using equivalent
Sour metformin mixing, stirs, standby.Then, 50% ethanol solution is added in mixed powder, soft material processed,
24 mesh sieves are pelletized, and are dried, 20 mesh sieve granulate, add micropowder silica gel, CMS-Na, are suppressed using suitable punch die after mix homogeneously
Tablet, obtains final product.It is coated to above-mentioned tablet, then obtains coated tablet, can is Film coated tablets, enteric coatel tablets etc..The preparation side
The granule poor compressibility obtained by method, tablet hardness are poor, and technology stability is poor.
Chinese patent application CN 101897697A discloses a kind of hypoglycemic medicine composition and purposes, and which is by the adjuvant in formula
Crushed 80 mesh sieves, drying for standby.Take 400g metformin, 5g vildagliptins, according to equal increments method mix homogeneously.
Starch, Microcrystalline Cellulose, shuttle methyl starch sodium and the light propyl cellulose of low replacement are separately added into according still further to formula ratio, are passed by equivalent
Increasing method uniformly mixes, and soft material is made with 5% 30 POVIDONE K 30 BP/USP 29/30-95% ethanol solution, and the granulation of 20 mesh sieves is done at 40 DEG C of temperature
Dry 2h, 18 mesh sieve granulate, the water content for making granule is 2%-3%, dried granule is mixed homogeneously with magnesium stearate and is made
Semi-finished product, semi-finished product are detected, determine content, tabletted with tablet machine.Made by tablet need to use aluminum-plastic blister bag
Dress, keeps in dark place.The method is loaded down with trivial details due to preparation technology, and constituent species are more, increased the uncontrollability of prescription and technique, from
And cause the robustness of formulation and technology poor.
In the formulation and technology containing vildagliptin and the pharmaceutical composition of metformin hydrochloride is prepared, shared by metformin hydrochloride
Large percentage, determine material it is always mixed after main character.Meanwhile, the poor compressibility of metformin hydrochloride, after result in total mixing
The compressibility of material is poor.If adopting wet granulation technology, granule is more closely knit, even if adding other adjuvants to be improved,
As its proportion is larger, both allowed tablet weight excessive, and be unfavorable for swallowing, technique can not have been met well and wanting for producing
Ask.Therefore, in the technique containing vildagliptin and the pharmaceutical composition of metformin hydrochloride is prepared, improve metformin hydrochloride
Compressibility just become the key factor for preparing sane controllable tablet.
The content of the invention
One of the object of the invention is the pharmaceutical composition for providing a kind of good vildagliptin of compressibility and metformin hydrochloride.
Invention has been first provided to a kind of pharmaceutical composition comprising vildagliptin and metformin hydrochloride, and which also includes following adjuvant：
Filler, binding agent, disintegrating agent and lubricant；The mass fraction of each component is：
Effective ingredient 68～78%；
Filler 9～15%；Binding agent 4～9%；Disintegrating agent 4～9%；Lubricant 0.3～1.5%.
Inventor has found the proportioning by control component, and the compressibility of compositionss can be caused to be optimized.
Grope to find by further test, using the compositionss containing following components (w/w), said medicine combination can be met
The compressibility of thing is required：Filler 9～15%；Binding agent 4～9%；Disintegrating agent 4～9%；Lubricant 0.3～1.5%.
Consider from the compressibility for further improving preparation, it is preferable that further control following condition：
Filler loading is controlled 10～12%；It is highly preferred that controlling 10.5～11%；
Disintegrating agent consumption is controlled 5～6%；It is highly preferred that controlling 5～5.5%；
Lubricant quantity is controlled 0.4～0.5%；It is highly preferred that controlling 0.43～0.49%.
In a preferred embodiment, in described effective ingredient, the weight ratio of vildagliptin and metformin hydrochloride is
2～5:65～75.
Alternatively, the filler is selected from Microcrystalline Cellulose；Binding agent is selected from hydroxypropyl cellulose, hydroxypropyl methylcellulose, gathers
One or more in dimension ketone and Copolyvidone；Disintegrating agent is selected from the poly- dimension of carboxymethylstach sodium, Croscarmellose Sodium and crosslinking
One or more in ketone；Lubricant is selected from one or more in sodium stearyl fumarate, Glyceryl Behenate and magnesium stearate.
Alternatively, described pharmaceutical composition also contains coating constituents OPADRY.
Aforementioned pharmaceutical compositions can be prepared by the following method acquisition：First metformin hydrochloride is individually pelletized, then again will
The metformin hydrochloride granule of preparation carries out mixing granulation with vildagliptin and adjuvant.
As preferred scheme, metformin hydrochloride can be pelletized using fluid bed top spray granulating process.
Method concrete steps：
(1) metformin hydrochloride is crushed；
(2) metformin hydrochloride is pelletized；
(3) the metformin hydrochloride granule obtained by step (2) is carried out into mixing granulation with vildagliptin and adjuvant；
(4) lubricant, mix homogeneously are added in the compositionss obtained by step (3)；
(5) tabletting is carried out to the total mixing composition obtained by step (4).
In a preferred embodiment of the present invention, the unit formulation content of metformin hydrochloride is 125mg-2000mg；Wei Gelie
The unit formulation content in spit of fland is 25mg-200mg.In further preferred embodiment of the present invention, the list of metformin hydrochloride
Position formulation content is 500mg-1000mg, and the unit formulation content of vildagliptin is 50mg-100mg.
In a preferred embodiment of the present invention, pharmaceutical composition of the invention is oral tablet.
In a preferred embodiment of the present invention, comprise the following specific steps that：
1st, metformin hydrochloride was crushed into 80 mesh sieves；
2nd, metformin hydrochloride is pelletized using fluid bed top spray granulating process；
3rd, the metformin hydrochloride granule and vildagliptin and pharmaceutically acceptable adjuvant obtained by step 2 is carried out into mixing granulation；
4th, lubricant, mix homogeneously are added in the compositionss obtained by step 3；
5th, tabletting is carried out to the total mixing composition obtained by step 4；
6th, the tablet obtained by step 5 is carried out into film coating.
In a preferred embodiment of the present invention, step 2 prepares binder solution first, is then added to metformin hydrochloride
In fluid bed, fluid bed top spray granulation is carried out with the binder solution of gained.
The invention provides a kind of pharmaceutical composition with metformin hydrochloride and vildagliptin as active component, efficiently solves list
Solely take conventional hypoglycemic medicine or vildagliptin is unable to the defect of effective control type 2 diabetes mellitus.
Importantly, poor compressibility of the present invention for metformin hydrochloride present in prior art, causes total mixed rear material
Poor compressibility defect.It is by selecting certain adjuvant and being allocated in specific amount ranges, first double to hydrochloride
Guanidine is individually pelletized, and then the metformin hydrochloride granule of preparation is carried out with vildagliptin and pharmaceutically acceptable adjuvant again
Mixing granulation, so as to effectively improve the robustness in tablet manufacture and controllability, favorable reproducibility, produce it is sane, can
Control, the tablet of favorable reproducibility, are adapted to industrialized production.
Description of the drawings
Fig. 1：The In-vitro release curves of pharmaceutical composition prepared by embodiment 1.
VGLT：Vildagliptin；EJSG：Metformin.
Fig. 2：The In-vitro release curves of pharmaceutical composition prepared by embodiment 2.
VGLT：Vildagliptin；EJSG：Metformin.
Fig. 3：The In-vitro release curves of pharmaceutical composition prepared by embodiment 3.
VGLT：Vildagliptin；EJSG：Metformin.
Fig. 4：The In-vitro release curves of pharmaceutical composition prepared by embodiment 4.
VGLT：Vildagliptin；EJSG：Metformin.
Fig. 5：The In-vitro release curves of pharmaceutical composition prepared by embodiment 5.
VGLT：Vildagliptin；EJSG：Metformin.
Specific embodiment
Below by embodiment, the present invention is described in further detail, it is intended to limits the present invention for illustrating rather than.
It should be pointed out that to those skilled in the art, under the premise without departing from the principles of the invention, the present invention can also be carried out
Some improvement and modification, these improve and modification similarly falls under the scope of the present invention.
Microcrystalline cellulose excipients used in following examples are purchased from FMC Corp., and hydroxypropyl cellulose is purchased from Ya Shilan companies,
Carboxymethylstach sodium is purchased from Distributions in Liaocheng of Shandong Province, and magnesium stearate is purchased from the Anhui mountains and rivers, and OPADRY is purchased from Ka Lekang." % " described in embodiment
Mass percent is, is separately had except especially indicating.
Unit used in following examples is conventional equipment well known in the art, and the fluid bed for using is Grant
GPCG2 types, high-speed mixing granulating machine are Xinyi spy's mini-CG types, and oscillatory type grinding bolting mill is powder Ruide MF-67 types,
Hoppertypeofblender is Canaan HBD100 types, and to create good WeiC ＆C800 types of winning, high-efficiency coating machine is letter to rotary tablet machine
Suitable spy's Labcoating1 types.
Embodiment 1：Preparation comprising vildagliptin and the pharmaceutical composition of metformin hydrochloride
1st, prescription：Specification 50mg/1000mg, recipe quantity are 1000.
| Supplementary material | Ratio (%) | Consumption (g) |
| Vildagliptin | 3.57 | 50 |
| Metformin hydrochloride | 71.42 | 1000 |
| Microcrystalline Cellulose PH102 | 11.16 | 156.25 |
| Hydroxypropyl cellulose EF | 5.36 | 75 |
| Carboxymethylstach sodium | 5.36 | 75 |
| Magnesium stearate | 0.45 | 6.25 |
| OPADRY | 2.68 | 37.5 |
| Amount to | 100 | 1400 |
2nd, preparation technology：
(1) accurately weigh above-mentioned supplementary material；
(2) metformin hydrochloride was crushed into 80 mesh sieves；
(3) binding agent hydroxypropyl cellulose EF is dissolved in appropriate water, is stirred to clarify, binding agent is completely dissolved, prepared
Composite adhesives solution；
(4) metformin hydrochloride is added in fluid bed, the binder solution prepared with step (3) carries out fluid bed top spray
Granulation；
(5) granule obtained by step (4) is mixed with vildagliptin, Microcrystalline Cellulose, carboxymethylstach sodium to uniform；
(6) magnesium stearate is added in the compositionss obtained by step (5), mix to uniform；
(7) the total mixing composition obtained by step (6) is carried out into tabletting, makes 1000；
(8) prepared tablet is carried out by film coating using OPADRY.
Embodiment 2：Preparation comprising vildagliptin and the pharmaceutical composition of metformin hydrochloride
1st, prescription：Specification 50mg/1000mg, recipe quantity are 1000.
| Supplementary material | Ratio (%) | Consumption (g) |
| Vildagliptin | 3.50 | 50 |
| Metformin hydrochloride | 69.93 | 1000 |
| Microcrystalline Cellulose PH102 | 10.90 | 160 |
| PVPK29/32 (is pelletized) | 3.64 | 52 |
| PVPK29/32 (mixes) | 3.64 | 52 |
| Carboxymethylstach sodium | 5.24 | 75 |
| Glyceryl Behenate | 0.49 | 6 |
| OPADRY | 2.66 | 38 |
| Amount to | 100 | 1433 |
2nd, preparation technology：
(1) accurately weigh above-mentioned supplementary material；
(2) metformin hydrochloride was crushed into 80 mesh sieves；
(3) PVPK29/32 (granulation) is dissolved in appropriate water, is stirred to clarify, binding agent is completely dissolved, prepared
Composite adhesives solution；
(4) metformin hydrochloride is added in fluid bed, the binder solution prepared with step (3) carries out fluid bed top spray
Granulation；
(5) granule obtained by step (4) is formed sediment with vildagliptin, PVPK29/32 (mixing), Microcrystalline Cellulose, carboxylic first
Powder sodium is mixed to uniform；
(6) Glyceryl Behenate is added in the compositionss obtained by step (5), mix to uniform；
(7) the total mixing composition obtained by step (6) is carried out into tabletting, makes 1000；
(8) prepared tablet is carried out by film coating using OPADRY.
Embodiment 3：Preparation comprising vildagliptin and the pharmaceutical composition of metformin hydrochloride
1st, prescription：Specification 50mg/1000mg, recipe quantity are 1000.
| Supplementary material | Ratio (%) | Consumption (g) |
| Vildagliptin | 3.33 | 50 |
| Metformin hydrochloride | 66.67 | 1000 |
| Microcrystalline Cellulose PH101 | 10.13 | 152 |
| PVPK29/32 (top spray granulation) | 3.47 | 52 |
| PVPK29/32 (wet granulation) | 3.47 | 52 |
| Carboxymethylstach sodium (interior to add) | 5.00 | 75 |
| Carboxymethylstach sodium (additional) | 5.00 | 75 |
| Magnesium stearate | 0.4 | 6 |
| OPADRY | 2.53 | 38 |
| Amount to | 100 | 1500 |
2nd, preparation technology：
(1) accurately weigh above-mentioned supplementary material；
(2) metformin hydrochloride was crushed into 80 mesh sieves；
(3) PVPK29/32 (top spray granulation) is dissolved in appropriate water, is stirred to clarify, binding agent is completely dissolved,
It is prepared into binder solution；
(4) metformin hydrochloride and carboxymethylstach sodium (interior to add) are added in fluid bed, the bonding prepared with step (3)
Agent solution carries out fluid bed top spray granulation；
(5) by granule obtained by step (4) and vildagliptin, PVPK29/32 (wet granulation), Microcrystalline Cellulose PH101,
Carboxymethylstach sodium (additional) is mixed to uniform；
(6) magnesium stearate is added in the compositionss obtained by step (5), mix to uniform；
(7) the total mixing composition obtained by step (6) is carried out into tabletting, makes 1000；
(8) prepared tablet is carried out by film coating using OPADRY.
Embodiment 4：Preparation comprising vildagliptin and the pharmaceutical composition of metformin hydrochloride
1st, prescription：Specification 50mg/1000mg, recipe quantity are 1000.
| Supplementary material | Ratio (%) | Consumption (g) |
| Vildagliptin | 3.62 | 50 |
| Metformin hydrochloride | 72.41 | 1000 |
| Microcrystalline Cellulose PH102 | 10.86 | 150 |
| Hydroxypropyl cellulose EF | 4.34 | 60 |
| Polyvinylpolypyrrolidone | 5.43 | 75 |
| Sodium stearyl fumarate | 0.43 | 6 |
| OPADRY | 2.90 | 40 |
| Amount to | 100 | 1381 |
2nd, preparation technology：
(1) accurately weigh above-mentioned supplementary material；
(2) metformin hydrochloride was crushed into 80 mesh sieves；
(3) binding agent hydroxypropyl cellulose EF is dissolved in appropriate water, is stirred to clarify, binding agent is completely dissolved, prepared
Composite adhesives solution；
(4) metformin hydrochloride is added in fluid bed, the binder solution prepared with step (3) carries out fluid bed top spray
Granulation；
(5) granule obtained by step (4) is mixed with vildagliptin, Microcrystalline Cellulose, polyvinylpolypyrrolidone to uniform；
(6) sodium stearyl fumarate is added in the compositionss obtained by step (5), mix to uniform；
(7) the total mixing composition obtained by step (6) is carried out into tabletting, makes 1000；
(8) prepared tablet is carried out by film coating using OPADRY.
Embodiment 5：Preparation comprising vildagliptin and the pharmaceutical composition of metformin hydrochloride
1st, prescription：Specification 50mg/1000mg, recipe quantity are 1000.
| Supplementary material | Ratio (%) | Consumption (g) |
| Vildagliptin | 3.54 | 50 |
| Metformin hydrochloride | 70.72 | 1000 |
| Microcrystalline Cellulose PH102 | 12.02 | 170 |
| Hydroxypropyl cellulose EF | 5.30 | 75 |
| Croscarmellose Sodium | 4.95 | 70 |
| Magnesium stearate | 0.50 | 7 |
| OPADRY | 2.97 | 42 |
| Amount to | 100 | 1414 |
2nd, preparation technology：
(1) accurately weigh above-mentioned supplementary material；
(2) metformin hydrochloride was crushed into 80 mesh sieves；
(3) binding agent hydroxypropyl cellulose EF is dissolved in appropriate water, is stirred to clarify, binding agent is completely dissolved, prepared
Composite adhesives solution；
(4) metformin hydrochloride is added in fluid bed, the binder solution prepared with step (3) carries out fluid bed top spray
Granulation；
(5) by granule obtained by step (4) mixed with vildagliptin, Microcrystalline Cellulose, Croscarmellose Sodium to
Uniformly；
(6) magnesium stearate is added in the compositionss obtained by step (5), mix to uniform；
(7) the total mixing composition obtained by step (6) is carried out into tabletting, makes 1000；
(8) prepared tablet is carried out by film coating using OPADRY.
Embodiment 6, release property test experience
1st, chromatographic condition：
(1) chromatographic column：XTerra C8(150×4.6mm,3.5um)；Numbering：R&D-02-006.
(2) column temperature：30℃；Detection wavelength：210nm (vildagliptin detection)；255nm (metformin detection)；
(3) mobile phase：15mmol/L potassium dihydrogen phosphates containing 0.05% sodium heptanesulfonate (phosphoric acid adjusts pH3.0)-acetonitrile
(90:10)；
(4) flow velocity：1.0ml/min.
2nd, release conditions：
Basket method；Rotating speed：100rpm；Temperature：37℃；Medium volume：900ml.Sample point be 5min, 10min, 15min,
20min、30min。
3rd, the preparation of reference substance solution：
(1) vildagliptin storing solution：Reference substance about 27.8mg is weighed, is placed in 20ml volumetric flasks, plus release medium dissolving,
Dilution, and constant volume.
(2) prepared by mixed reference substance solution：Metformin reference substance about 27.8mg is weighed, is placed in 25ml volumetric flasks, plus
Release medium dissolves in right amount, adds and states vildagliptin storing solution 1ml, plus release medium dilution constant volume.
4th, the preparation (preparing with reference to European standard) of release medium：
PH1.0 hydrochloric acid solution release medium：Take 9ml hydrochloric acid and be placed in 1L degassing ultra-pure waters and dissolve and obtain final product.
The In-vitro release curves of the pharmaceutical composition that embodiment 1-5 is prepared respectively referring to Figure of description 1-5, wherein VGLT are
Vildagliptin, EJSG are metformin.From the point of view of release conditions, in pH1.0 hydrochloric acid solution release medium, embodiment 1-5
Middle vildagliptin and metformin hydrochloride reach stable release, such as Fig. 1-5, and meet release request.
Embodiment 7, with the compressibility of pharmaceutical composition made by different auxiliary material, Dissolution experiments
Vildagliptin, metformin hydrochloride medicinal composition are prepared with different auxiliary material.The similar above-described embodiment of preparation process.Test
The compressibility index of compositionss and Hao Sina ratios.
Method of testing：The powder before tabletting is weighed, is placed in measurement graduated cylinder (100ml), is started according to jolt ramming instrument working specification and shake
Dynamic component.Compressibility index and Hao Sina ratios are calculated by following equation：
The prescription of different pharmaceutical compositionss is as shown in table 1, table 2.
The pharmaceutical composition composition and its compressibility index and Hao Sina ratios (1) of 1. different prescriptions of table
The pharmaceutical composition composition and its compressibility index and Hao Sina ratios (1) of 2. different prescriptions of table
After being prepared into pharmaceutical composition, dissolution experiment is further carried out.Experimental technique such as embodiment 6.As a result it is as shown in table 3.
Dissolution rate (%) (1) of the 3. different prescription drugs of table in different time points
Dissolution rate (%) (2) of the 4. different prescription drugs of table in different time points
From result, the compressibility of the present composition is preferable, and stable effective ingredients ground dissolution, and final release rate is high.
The present composition can substantially improve the problem of the poor compressibility of metformin hydrochloride present in prior art.From further carrying
The compressibility of high preparation considers, in above-mentioned exemplary prescription, the best results of prescription 2,4, and compressibility index is 13.7
Or it is following.
1 mixing granulation method of comparative example
Using mixing granulation method, the mixing granulation of vildagliptin and metformin hydrochloride is carried out according to following prescription.
5 mixing granulation method prescription of table
As a result as shown in table 6,7.
6. vildagliptin uniformity of dosage units of table
7. compressibility index of table and Hao Sina ratios
| Compressibility index | 20.7% |
| Hao Sina ratios | 1.45 |
It can be seen that, if the method for comparative selection example 1 carries out mixing granulation, it may appear that the medicament contg uniformity and mobility it is not good and
The excessive problem of tablet weight variation, compressibility are deteriorated.
Claims (10)
1. the pharmaceutical composition of vildagliptin and metformin hydrochloride is included, and which includes effective ingredient vildagliptin and hydrochloride is double
Guanidine, it is characterised in that also comprising adjuvant：Filler, binding agent, disintegrating agent and lubricant；The mass fraction of each component is：
Effective ingredient 68～78%；
Filler 9～15%；Binding agent 4～9%；Disintegrating agent 4～9%；Lubricant 0.3～1.5%.
2. pharmaceutical composition as claimed in claim 1, it is characterised in that in described effective ingredient, vildagliptin and hydrochloric acid two
The weight ratio of first biguanide is 2～5:65～75.
3. the pharmaceutical composition as described in claim 1～2 is arbitrary, it is characterised in that the filler loading control is 10～12%；
It is highly preferred that controlling 10.5～11%.
4. the pharmaceutical composition as described in claim 1～2 is arbitrary, it is characterised in that the disintegrating agent consumption control is 5～6%；
It is highly preferred that controlling 5～5.5%.
5. the pharmaceutical composition as described in claim 1～2 is arbitrary, it is characterised in that the lubricant quantity control is 0.4～0.5%；
It is highly preferred that controlling 0.43～0.49%.
6. the pharmaceutical composition as described in claim 1～2 is arbitrary, it is characterised in that the filler is selected from Microcrystalline Cellulose；It is viscous
Mixture is selected from one or more in hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvidone and Copolyvidone；Disintegrating agent is selected from
One or more in carboxymethylstach sodium, Croscarmellose Sodium and polyvinylpolypyrrolidone；Lubricant is selected from stearoyl-fumarate
One or more in sodium, Glyceryl Behenate and magnesium stearate.
7. the pharmaceutical composition as described in claim 1～2 is arbitrary, it is characterised in that also containing coating constituents OPADRY.
8. the preparation method of pharmaceutical composition as claimed in claim 1, it is characterised in that first metformin hydrochloride is individually made
Then the metformin hydrochloride granule of preparation is carried out mixing granulation with vildagliptin and adjuvant by grain again.
9. pharmaceutical composition as claimed in claim 1, wherein being carried out to metformin hydrochloride using fluid bed top spray granulating process
Granulation.
10. method as claimed in claim 9, which comprises the following specific steps that：
(1) metformin hydrochloride is crushed；
(2) metformin hydrochloride is pelletized；
(3) the metformin hydrochloride granule obtained by step (2) is carried out into mixing granulation with vildagliptin and adjuvant；
(4) lubricant, mix homogeneously are added in the compositionss obtained by step (3)；
(5) tabletting is carried out to the total mixing composition obtained by step (4).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510639366.8A CN106551927A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510639366.8A CN106551927A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106551927A true CN106551927A (en) | 2017-04-05 |
Family
ID=58417275
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510639366.8A Pending CN106551927A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106551927A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019219920A1 (en) * | 2018-05-18 | 2019-11-21 | Galenicum Health S.L.U | Stable pharmaceutical compositions of dpp-iv inhibitors in combination with metformin in the form of immediate release tablets |
| CN114306267A (en) * | 2020-09-30 | 2022-04-12 | 深圳翰宇药业股份有限公司 | Sitagliptin and metformin tablet preparation and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN101897697A (en) * | 2009-05-27 | 2010-12-01 | 北京奥萨医药研究中心有限公司 | Sugar-lowering drug composition and application |
| CN103705515A (en) * | 2013-12-27 | 2014-04-09 | 华润赛科药业有限责任公司 | Method for preparing pharmaceutical composition containing repaglinide and metformin hydrochloride |
| 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 |
-
2015
- 2015-09-30 CN CN201510639366.8A patent/CN106551927A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN101897697A (en) * | 2009-05-27 | 2010-12-01 | 北京奥萨医药研究中心有限公司 | Sugar-lowering drug composition and application |
| CN103705515A (en) * | 2013-12-27 | 2014-04-09 | 华润赛科药业有限责任公司 | Method for preparing pharmaceutical composition containing repaglinide and metformin hydrochloride |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| 崔德福: "《药剂学（第二版）》", 31 January 2011, 中国医药科技出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019219920A1 (en) * | 2018-05-18 | 2019-11-21 | Galenicum Health S.L.U | Stable pharmaceutical compositions of dpp-iv inhibitors in combination with metformin in the form of immediate release tablets |
| CN114306267A (en) * | 2020-09-30 | 2022-04-12 | 深圳翰宇药业股份有限公司 | Sitagliptin and metformin tablet preparation and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5779566B2 (en) | Pharmaceutical composition comprising a combination of a dipeptidyl peptidase-4 inhibitor and metformin | |
| JP2020055816A5 (en) | ||
| RU2493844C2 (en) | Double-action pharmaceutical compositions of submolecular structure of angiotensin receptor blocker (arb) and neutral endopeptidase (nep) inhibitor | |
| CN103655539B (en) | A kind of oral solid formulation of canagliflozin and preparation method thereof | |
| JP2011513408A (en) | Combination pharmaceutical composition of metformin and dipeptidyl peptidase-IV inhibitor | |
| JP2011510986A (en) | Combination pharmaceutical composition of metformin and dipeptidyl peptidase-IV inhibitor | |
| CN108653226A (en) | The daily single administration sustained release preparation of Mosapride of pharmacology and clinical effect is provided | |
| JP2005508331A (en) | Dosage preparation for the treatment of diabetes | |
| JP4848558B2 (en) | Rapid-release tablets containing metformin hydrochloride | |
| WO2004054574A1 (en) | Solid drug for oral use | |
| JP2013508370A (en) | Pharmaceutical composition comprising a combination of a dipeptidyl peptidase-4 inhibitor and pioglitazone | |
| US20060240101A1 (en) | Orally disintegrating pharmaceutical tablet formulations of olanzapine | |
| CN105456270A (en) | Dipeptidyl peptidase IV inhibitor pharmaceutical composition, use and preparation method thereof | |
| CN102499923B (en) | Drug combination, as well as preparation method and application of same | |
| JP2020114834A (en) | Ceritinib formulation | |
| CN103520128A (en) | Pramipexole sustained-release tablet, preparation method and application thereof | |
| CN106551927A (en) | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof | |
| CN103251594B (en) | Repaglinide/metformin combo tablet | |
| CN100525760C (en) | Duloxetine hydrochloride sustained release medicine | |
| JP2023514005A (en) | Composite preparation containing sitagliptin and dapagliflozin and method for producing the same | |
| KR20190000661A (en) | Once a day oral dosage sustained-release formulation comprising mosapride | |
| CN104739835A (en) | Novel pharmaceutical composition for treating diabetes | |
| CN109010298B (en) | Metformin and glipizide compound composition and preparation method thereof | |
| WO2013189305A1 (en) | Valsartan-amlodipine compound solid preparation and preparation method therefor | |
| TWI436760B (en) | Galenical formulations of aliskiren |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170405 |
|
| RJ01 | Rejection of invention patent application after publication |