CN105078913B - A kind of Irbesartan Tablets and preparation method thereof - Google Patents
A kind of Irbesartan Tablets and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of Irbesartan Tablets and preparation method thereof.The Irbesartan Tablets are made up of following raw material by mass parts：150~450 parts of Irbesartan, 15~50 parts of montmorillonite, 85~270 parts of sucrose, 0.5~1.5 part of magnesium stearate, 0.5~1.5 part of silica.The present invention also provides the preparation method of Irbesartan Tablets.Cooperation of the invention by specific auxiliary material and main ingredient, and specific proportioning, solve the problems such as existing drug particles mobility is bad, medicine disintegration is undesirable, drug dissolution is low, stability is poor and human bioavailability is not high.
Description
Technical field
The present invention relates to a kind of Irbesartan Tablets and preparation method thereof, belong to pharmaceutical technology field.
Background technology
According to the ill statistics of Chinese high blood pressure in 2002, adult hypertension illness rate in China's is national up to 18.8% at present
Hypertension total number of persons nearly 1.6 hundred million.The various complication caused by high blood pressure, it is the important original for triggering cranial vascular disease dead
Cause.Therefore, hypertension how is effectively prevented and treated, reduces or reduce the various complication as caused by hypertension, is to improve China human mortality
Quality, reduce the important measures of mortality of cardio and cerebral vascular disease.
Irbesartan Tablets are angiotensinⅡ (Angiotensin II, Ang II) acceptor inhibitor, can suppress I turn of Ang
Turn to Ang II, can the specifically acceptor of antagonizing angiotensin converting Enzyme 1 (AT1), AT28500 is more than to AT1 antagonism
Times, by optionally blocking Ang II and AT1 acceptors combination, suppress the release of vessel retraction and aldosterone, produce decompression and make
With.This product does not suppress Angiotensin-Converting (ACE), feritin, other hormone receptors, does not suppress to put down with blood pressure control and sodium yet
Weigh relevant ion channel.
China's hypertension drug market potential is huge, and because the living standard of people improves, work competition growing tension is high
Blood pressure number of patients greatly increases, and especially still will be enlarged by, drops in economical gradually developing northern the greater part, Hypertensive Population
Pressing has the larger market demand.
Though China's pharmaceutical market is still occupied an leading position with calcium antagonist and ACEI at present, ACEI increases comparatively fast, although to sand
The positioning of the definite indication of smooth class medicine (single dose and compound preparation), is only limited to hypertension, to the clinic of other indications at present
Data waits to accumulate, but the side reactions such as excellent antihypertensive effect, dry cough are low because husky smooth class has, and the compliance of patient is good, and
And existing several years Clinical practice basis, there is certain popularity in hospital doctor.Losartan ELITE-2 result of the tests make sand
Smooth kind new medicine is by major defeat, it is meant that the loss of market of such medicine in terms of heart failure treatment, but brand-new negative booster
System makes sartans have preferable market point of penetration (such as：Steadily it is depressured, side reaction is low, without dry cough acceptor levels suppression etc.).
Chinese patent document CN103191076A discloses a kind of Irbesartan tablet preparation method, and Irbesartan is dissolved in
In sodium hydrate aqueous solution, dried and pharmaceutic adjuvant mixed pressuring plate after adding PVPP absorption；Its purpose of this method in order to
Solving the dissolution rate of medicine, Irbesartan is dissolved in sodium hydroxide solution, has changed the physicochemical property of medicine by this method, and
New material is generated, may clinically bring other unknown effects.
Chinese patent document CN102309456B discloses a kind of Irbesartan sodium micro composite powder and tablet and its preparation
Method, it, which is used, is dissolved in Irbesartan in organic solvent, adds pharmaceutic adjuvant and is well mixed, be spray-dried, is prepared
Go out amorphous and crystal type Irbesartan sodium micro composite powder, with tabletting after mix lubricant, its purpose is to solve for this method
The certainly dissolution rate of medicine, but due to that by high temperature spray-drying method, medicine and auxiliary material may be made to be caused in hot environment
Unstability factor, make the relevant material of preparation of Irbesartan against regulation.
Because Irbesartan is non-solubization medicine, and the disintegration of existing preparation is slow, and uses routine prescription and routine
Preparation technology and auxiliary material, it is difficult to solve the relatively low technical barrier of bioavilability in drug dissolution and human body.Therefore
A kind of steady quality is found, safe and effective Irbesartan tablet recipe and auxiliary material and preparation technology have become matter of utmost importance.
The content of the invention
In view of the shortcomings of the prior art, the present invention provides a kind of Irbesartan Tablets and preparation method thereof.By specific auxiliary
Material and the cooperation of main ingredient, and specific proportioning, solve that existing drug particles mobility is bad, medicine disintegration is undesirable, medicine
The problems such as thing dissolution rate is low, stability is poor and human bioavailability is not high.
Technical scheme is as follows：
A kind of Irbesartan Tablets, it is made up of following raw material by mass parts：
, according to the invention it is preferred to,
A kind of Irbesartan Tablets, it is made up of following raw material by mass parts：
According to the present invention, it is further preferred that
A kind of Irbesartan Tablets, it is made up of following raw material by mass parts：
Or a kind of Irbesartan Tablets, it is made up of following raw material by mass parts：
Or a kind of Irbesartan Tablets, it is made up of following raw material by mass parts：
Irbesartan Tablets of the present invention, wherein described montmorillonite is medicinal smectite.Original used in the present invention
Expect that not specified is conventional commercial products.
The preparation method of Irbesartan Tablets of the present invention, comprises the following steps：
(1) Irbesartan, sucrose, montmorillonite are crushed into sieving for standby；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then add second made from step (2)
Alcohol solution, it is uniformly mixed and softwood is made, sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried, sieving whole grain obtains dry particl, standby；
(5) addition magnesium stearate, silica are well mixed with dry particl made from step (4), and tabletting produces.
, according to the invention it is preferred to,
Irbesartan described in step (1), cross 80~100 mesh sieves；Described sucrose, cross 110~130 mesh sieves；It is described
Montmorillonite, cross 350~400 mesh sieves.
The addition of ethanol water described in step (3) is 5~10% (w/w) of total solid substance.
Drying described in step (4) is dried 1~4 hour under the conditions of 45~60 DEG C；The sieving whole grain was 16~
24 mesh sieves；The moisture of described dry particl be 3% (w/w) below.
Described Irbesartan Tablets medicine piece is 0.25~0.30g/ pieces again.
The Irbesartan Tablets of the present invention are safe efficient, quality controllable, easy to use, the piece and existing Irbesartan medicine
Compare, be whether formulated or have significant distinctive feature in preparation method.Specially：
1st, Irbesartan Tablets pharmaceutical formulation application montmorillonite of the invention is disintegrant so that in Irbesartan Tablets significantly
Reduction auxiliary material species and usage amount, disintegration time and dissolution rate significantly improve, and Irbesartan tablet stability is good, work
Skill is easy.
2nd, filler sucrose is added in the present invention, wherein sucrose plays filler effect in Irbesartan Tablets, rises again
Acted on to adhesive, the wherein addition of sucrose further cooperates with montmorillonite peptizaiton, promotes the disintegration rate of Irbesartan Tablets.
In summary, the invention provides a kind of Irbesartan Tablets medicine that can be disintegrated rapidly, drastically increase and collapse
Speed is solved, dissolution rate is high；On the premise of ensuring that Irbesartan Tablets medicine meets quality standard while cause its therapeutic efficiency not
It is impacted and improve human bioavailability, there is great strategic structural, good market prospect.
With reference to experimental example, the present invention is described further, but not limited to this.
Experimental example 1：The screening experiment of disintegrant
In the present invention, the species of disintegrant and the dissolution rate of Irbesartan Tablets and bioavilability are closely related.At present,
During preparation research, the most frequently used disintegrant has：Sodium carboxymethyl starch (CMS-Na), low-substituted hydroxypropyl cellulose
(LHPC), nearly 20 kinds of PVPP (PVPP) etc., the disintegrant itself in tablet have stronger suction mostly
Hydroexpansivity, so as to disintegrate the adhesion of tablet.Usually said high-quality disintegrant refers to water absorption and swelling degree collapsing more than 5ml/g
Agent is solved, expansion rate is bigger, and disintegration effect is more notable.The selection of disintegrant is one of factor important in tablet formulation design, is ground
Study carefully the disintegrant of exploitation function admirable, or preparation work from suitable disintegrant and is improved according to the characteristic of different disintegrants
Skill, it will make the tablet of development there is more excellent Release Performance.
1st, to montmorillonite and sodium carboxymethyl starch (CMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crosslinked polyethylene
Pyrrolidones (PVPP), the water swelling degree of pregelatinized starch carry out experimental study；It is shown in Table 1.
Table 11g samples fully absorb water after weight and volume number
| Disintegrant | Weight (g) after water suction | Volume (ml) after water suction |
| Low-substituted hydroxypropyl cellulose (LHPC) | 6.32±0.28 | 7.6±0.2 |
| Pregelatinized starch | 8.57±0.17 | 10.4±0.2 |
| Sodium carboxymethyl starch (CMS-Na) | 19.29±0.21 | 20.4±0.3 |
| PVPP (PVPP) | 4.04±0.13 | 5.6±0.2 |
| Montmorillonite | 18.78±0.24 | 19.8±0.3 |
It is larger by the swelling volume that montmorillonite can be analyzed in table 1, it is 19.8ml/g；Slightly smaller than sodium carboxymethyl starch
(CMS-Na), more than other disintegrants.
2nd, the comparative studies of montmorillonite and the disintegrating property of conventional disintegrant；The present invention prepares blank model using calcium carbonate
Piece, using the hardness of tablet and disintegration time limited as inspection target, experimental study is carried out to the disintegrating property of montmorillonite：It is shown in Table 2.
Several disintegrant hardness of table 2 and disintegration time compare
| Disintegrant | Hardness (N) | Disintegration time (minute) |
| Calcium carbonate (blank model piece) | 57 | ＞ 2 hours |
| Low-substituted hydroxypropyl cellulose (L-HPC) | 51 | 4.32±1.11 |
| Pregelatinized starch | 49 | 6.16±0.83 |
| Sodium carboxymethyl starch (CMS-Na) | 56 | 3.16±0.64 |
| PVPP (PVPP) | 56 | 2.02±0.87 |
| Montmorillonite | 54 | 2.23±0.96 |
Analyzed by table 2, in hardness in the case of, when being not added with disintegrant, during the disintegration of calcium carbonate blank model piece
Between more than two hours, add the tablet of disintegrant, disintegration time substantially shortens, wherein PVPP (PVPP)
Disintegration time is most short, and montmorillonite is better than other disintegrants.
Tested by table 1,2 and studied, the present invention is from the disintegrant that montmorillonite is Irbesartan Tablets.
Experimental example 2：Prescription screening is tested
The auxiliary material of this tablet institute plan is pharmaceutic adjuvant grade, for this preparation characteristic and combines tablet R＆D experience, if
Count the prescription of preliminary screening.Character, friability, disintegration time, dissolution rate are investigated respectively, and pay attention to observing preparation process
Phenomenon.It is shown in Table 3.
(the unit of 3 Irbesartan Tablets prescription screening of table 1：g)
| Component | 01 | 02 | 03 |
| Irbesartan | 150 | 150 | 150 |
| Montmorillonite | 3 | 6 | 9 |
| Sucrose | 98 | 98 | 98 |
| Magnesium stearate | 0.5 | 0.5 | 0.5 |
| Silica | 0.5 | 0.5 | 0.5 |
Preparation method：Prepare 75% (w/w) ethanol solution；
Supplementary material Irbesartan, sucrose, montmorillonite are taken, is well mixed, adhesive ethanol water is added and prepares softwood, mistake
Wet granular is made in 20 mesh sieves；
Wet granular is dried under the conditions of 50 ± 5 DEG C, 16 mesh sieve whole grains；
Add magnesium stearate lubricant, silica is well mixed；
Justify stamping with 9mm dimple forms.
Each prescription is tested, as a result see the table below 4：
The prescription screening of table 4 tests 1 assay
| Supplementary material | 01 | 02 | 03 |
| Character | It is unilateral not clean | It is unilateral bright and clean | It is unilateral bright and clean |
| Friability | Meet regulation | Meet regulation | Meet regulation |
| Disintegration time (min) | 30 | 26 | 17 |
| Remarks | Compressibility is very poor, can not tabletting | Mobility of particle is poor, the more difficult control of piece weight | Disintegration time is longer |
Interpretation of result：The particle compressibility of prescription 1 is too poor, and easy sticking leads to not normal tabletting, and disintegration time is longer,
Abandon.The mobility of particle of prescription 2 is poor, and uncontrollable weight, another disintegration time is oversize, abandons.The preparation process of prescription 3 is more suitable
Profit, but tablet disintegration times are longer, can influence subsequent product dissolution determination, therefore supplementary product kind, dosage are adjusted according to prescription 3,
Continue to screen prescription.It is shown in Table 5.
(the unit of 5 prescription screening of table 2：g)
| Component | 04 | 05 | 06 |
| Irbesartan | 150 | 150 | 150 |
| Montmorillonite | 12 | 14 | 16 |
| Sucrose | 98 | 98 | 98 |
| Magnesium stearate | 0.5 | 0.5 | 0.5 |
| Silica | 0.5 | 0.5 | 0.5 |
Preparation method：Prepare 80% (w/w) ethanol solution；
Supplementary material Irbesartan, sucrose, montmorillonite are taken, is well mixed, adhesive ethanol water is added and prepares softwood, mistake
Wet granular is made in 20 mesh sieves；
Wet granular is dried under the conditions of 50 ± 5 DEG C, 16 mesh sieve whole grains；
Add magnesium stearate lubricant, silica is well mixed；
Justify stamping with 9mm dimple forms.
Each prescription is tested, as a result see the table below 6：
The prescription screening of table 6 tests 2 assays
| Supplementary material | 04 | 05 | 06 |
| Character | It is unilateral bright and clean | It is unilateral bright and clean | It is unilateral bright and clean |
| Friability | Meet regulation | Meet regulation | Meet regulation |
| Disintegration time | 12 | 10 | 6 |
| Dissolution rate | 31.4 | 73.40 | 95.50 |
| Content | 99.27 | 100.12 | 99.80 |
| Remarks | Disintegration time is longer, dissolution is very poor | Dissolution is relatively low | Well |
Conclusion：The tablet disintegration times of prescription 4 are longer, and dissolution is too low, abandon.The tablet dissolution of prescription 5 is relatively low, unqualified,
Abandon.The gained tablet items of prescription 6 are good.So determine the optimal prescription that prescription 6 is this preparation.
Experimental example 3：Supplementary material compatibility experiments
The montmorillonite selected during Irbesartan Tablets drug research of the present invention as disintegrant, sucrose as filler,
Supplementary material compatibility test is as follows；
By raw material and selected auxiliary material physical mixed by a certain percentage, according to Chinese Pharmacopoeia 2010 edition two (C of annex Ⅺ Ⅹ)
The experimental method of influence factor in bulk drug and pharmaceutical preparation stability test guideline, respectively in 60 DEG C ± 2 DEG C of high temperature, wet
Placed 10 days under conditions of degree 90% ± 5%, strong 4500 ± 500lx of light, check and place front and rear change.Result of the test is as follows：
1st, hot conditions supplementary material compatibility test
Supplementary material is mixed according to a certain percentage, exposure was put under the conditions of 60 DEG C ± 2 DEG C of high temperature 10 days, respectively at 0,5,10 day
Sampling, assay see below 7 tables.
7 supplementary material compatibility test of table 10 days
Through 10 days compatibility tests under the conditions of 60 DEG C ± 2 DEG C of high temperature, each auxiliary material character, relevant material, content are as a result shown
It is unchanged.Moisture inspection result shows with time lengthening and reduced.
Result above shows that Irbesartan is good with auxiliary material compatibility under the conditions of 60 DEG C ± 2 DEG C of high temperature.
2nd, super-humid conditions supplementary material compatibility test
Supplementary material is mixed according to a certain percentage, exposure is put under the conditions of high humidity (90% ± 5%) 10 days, respectively at 0,5,10
Its sampling, determines indices, as a result sees 8 tables.
Sample is divides equally three parts of progress, three condition tests after weighing, therefore 10 days results of high humidity were the same as high temperature 10 days.
8 supplementary material compatibility test high humidity (90% ± 5%) of table 10 days
Through 10 days compatibility tests under the conditions of high humidity 90% ± 5%, each auxiliary material character, relevant material, content are as a result shown
It is unchanged.Because this law is that material is exposed under super-humid conditions, therefore some projects moisture increased.
Result above shows that Irbesartan is good with auxiliary material compatibility under the conditions of high humidity 90% ± 5%.Compbined test knot
Fruit shows that preparation should be sealed.
3rd, illumination condition supplementary material compatibility test
Supplementary material is mixed according to a certain percentage, exposure is put under the conditions of illumination (4500 ± 500lx) 10 days, respectively at 0,5,
Sample within 10 days, measure Irbesartan content the results are shown in Table 9 compared with 0 day.
0 day result of illumination was the same as high temperature 0 day.
9 supplementary material compatibility test illumination (4500 ± 500lx) of table 10 days
Through 10 days compatibility tests under the conditions of illumination (4500 ± 500lx), as a result show each auxiliary material character, relevant material,
Content is unchanged, because this law is that therefore some projects moisture increased under material exposure condition
Result above shows that Irbesartan is good with auxiliary material compatibility under the conditions of illumination (4500 ± 500lx).
Shown through supplementary material compatibility test under three kinds of experimental conditions, all samples items leading indicator and raw material are more equal
Without significant change, show that Irbesartan is respectively provided with preferable compatibility with above-mentioned auxiliary material, selected auxiliary material is reasonable.
To sum up test result indicates that：Disintegrant in the Irbesartan Tablets medicine of the present invention uses montmorillonite；Filler is adopted
Sucrose, wherein sucrose draw moist relatively strong, and water swellability of the montmorillonite in water is 19.8ml/g, both auxiliary materials
Synergy, so that Irbesartan Tablets dispersion of medicine is good, dissolution rate is high, and simple process, and industrialization degree is high,
For auxiliary material using less, production cost is low.
Brief description of the drawings
Fig. 1 is the Irbesartan Tablets medicine Irbesartan Dissolution profiles figure of embodiment 1；
Fig. 2 is the Irbesartan Tablets medicine Irbesartan Dissolution profiles figure of embodiment 2；
Fig. 3 is the Irbesartan Tablets medicine Irbesartan Dissolution profiles figure of embodiment 3.
Fig. 4 is the average Dissolution profiles figure of Irbesartan Tablets medicine Irbesartan of embodiment 1,2,3.
Embodiment
With reference to embodiment, the present invention is described further, but not limited to this.
Supplementary material source is described as follows in embodiment：
| Supplementary material title | Manufacturing enterprise | Execution standard |
| Irbesartan | Xiuzheng Pharmaceutical Group Liuhe Pharmaceutical Co., Ltd. | National drug standards WS1- (X-005) -2005Z |
| Montmorillonite | Shandong Xian He pharmaceutical Co. Ltds | 2010 editions addendums of Chinese Pharmacopoeia |
| Sucrose | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 edition two |
| Magnesium stearate | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 edition two |
| Silica | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 edition two |
| Medicinal alcohol (95%) | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 edition two |
| Purified water | Shandong Sibangde Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 edition two |
Involved device and equipment are solid pharmaceutical preparation production common apparatus in embodiment, and market is commercially available.It is described as follows:
Universal high-efficiency pulverizer (model 30B), square shaking screen (model FS-0.5M2-X), high-speed mixing granulating machine (type
Number GHL200), oscillating granulator (model YK320), heated-air circulation oven (model C T- III), three-dimensional motion mixer (model
SYH-800) above equipment：Changzhou Teng Longyaohua equipment Co., Ltd is on sale.
Full-automatic double discharging high speed tablet presses (model GZPS-49)：Beijing Hanlin Hangyu Technology Development Co., Ltd. is on sale.
Embodiment 1：The preparation of Irbesartan Tablets
Irbesartan Tablets, it is made up of following raw material by mass parts：
Preparation method is as follows：
(1) by Irbesartan, sucrose, montmorillonite, crush；Wherein it is standby to cross 90 mesh sieves for Irbesartan；Sucrose crosses 120 mesh sieves
It is standby；It is standby that montmorillonite crosses 350 mesh sieves；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then added 75 made from step (2)
~80% (w/w) ethanol water, is uniformly mixed and softwood is made, and sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried 1.5 hours at 50~52 DEG C, detects pellet moisture 2.5%, mistake
25 mesh sieve whole grains, it is standby；
(5) metering part magnesium stearate is added, silica is well mixed with dry particl made from step (4), particle 9mm
Dimple form circle stamping obtains Irbesartan Tablets.
Testing result：
Appearance film type is complete, smooth, and dispersing uniformity meets regulation, and the relevant material of Irbesartan is (1) 0.12%, (2)
0.13%th, (3) 0.25 (refer to that Irbesartan has three relevant materials, generally with 1,2,3 come table about material (1), (2), (3)
State), the Irbesartan Tablets dissolution rate of 30 minutes is 99.23%.The content of Irbesartan is 99.53%, and other indexs meet
Regulation.
The preparation of the Irbesartan Tablets of embodiment 2：
Irbesartan Tablets, it is made up of following raw material by mass parts：
Preparation method is as follows：
(1) by Irbesartan, sucrose, montmorillonite, crush；Wherein it is standby to cross 80 mesh sieves for Irbesartan；Sucrose crosses 110 mesh sieves
It is standby；It is standby that montmorillonite crosses 400 mesh sieves；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then added 75 made from step (2)
~80% (w/w) ethanol water, is uniformly mixed and softwood is made, and sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried 1 hour at 53~55 DEG C, detects pellet moisture 2.3%, cross 30
Mesh sieve whole grain, it is standby；
(5) metering part magnesium stearate is added, silica is well mixed with dry particl made from step (4), particle 9mm
Dimple form circle stamping obtains Irbesartan Tablets.
Testing result：
Appearance film type is complete, smooth, and dispersing uniformity meets regulation, and the relevant material of Irbesartan is (1) 0.11%, (2)
0.12% (3) 0.26, the Irbesartan dissolution rate of 30 minutes are 98.39%.The content of Irbesartan is 99.6%, other indexs
Meet regulation.
The preparation of the Irbesartan Tablets of embodiment 3：
Irbesartan Tablets, it is made up of following raw material by mass parts：
Preparation method is as follows：
(1) by Irbesartan, sucrose, montmorillonite, crush；Wherein it is standby to cross 80 mesh sieves for Irbesartan；Sucrose crosses 130 mesh sieves
It is standby；It is standby that montmorillonite crosses 370 mesh sieves；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then added 75 made from step (2)
~80% (w/w) ethanol water, is uniformly mixed and softwood is made, and sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried 1.2 hours at 52~54 DEG C, detects pellet moisture 2.15%, mistake
40 mesh sieve whole grains, it is standby；
(5) metering part magnesium stearate is added, silica is well mixed with dry particl made from step (4), particle 9mm
Dimple form circle stamping obtains Irbesartan Tablets.
Testing result：
Appearance film type is complete, smooth, and dispersing uniformity meets regulation, and the relevant material of Irbesartan is (1) 0.13%, (2)
0.11% (3) 0.27, the Irbesartan dissolution rate of 30 minutes are 97.14%.The content of Irbesartan is 100.01%；Other fingers
Mark meets regulation.
The preparation of the Irbesartan Tablets of embodiment 4：
Irbesartan Tablets, it is made up of following raw material by mass parts：
Preparation method is as follows：
(1) by Irbesartan, sucrose, montmorillonite, crush；Wherein it is standby to cross 100 mesh sieves for Irbesartan；Sucrose crosses 120 mesh
Sieve standby；It is standby that montmorillonite crosses 350 mesh sieves；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then added 75 made from step (2)
~80% (w/w) ethanol water, is uniformly mixed and softwood is made, and sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried 2 hours at 55~57 DEG C, detects pellet moisture 2.35%, cross 20
Mesh sieve whole grain, it is standby；
(5) metering part magnesium stearate is added, silica is well mixed with dry particl made from step (4), particle 9mm
Dimple form circle stamping obtains Irbesartan Tablets.
Testing result：
Appearance film type is complete, smooth, and dispersing uniformity meets regulation, and the relevant material of Irbesartan is (1) 0.13%, (2)
0.12% (3) 0.26, the Irbesartan dissolution rate of 30 minutes are 96.70%.The content of Irbesartan is 99.70%；Other fingers
Mark meets regulation.
The preparation of the Irbesartan Tablets of embodiment 5：
Irbesartan Tablets, it is made up of following raw material by mass parts：
Preparation method is as follows：
(1) by Irbesartan, sucrose, montmorillonite, crush；Wherein it is standby to cross 80 mesh sieves for Irbesartan；Sucrose crosses 110 mesh sieves
It is standby；It is standby that montmorillonite crosses 350 mesh sieves；
(2) 95% (w/w) medicinal alcohol is added into purified water and is configured to 75~80% (w/w) ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then added 75 made from step (2)
~80% (w/w) ethanol water, is uniformly mixed and softwood is made, and sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried 1 hour at 53~55 DEG C, detects pellet moisture 2.3%, cross 30
Mesh sieve whole grain, it is standby；
(5) metering part magnesium stearate is added, silica is well mixed with dry particl made from step (4), particle 9mm
Dimple form circle stamping obtains Irbesartan Tablets.
Testing result：
Appearance film type is complete, smooth, and dispersing uniformity meets regulation, and the relevant material of Irbesartan is (1) 0.12%, (2)
0.11% (3) 0.25, the Irbesartan dissolution rate of 30 minutes are 98.70%.The content of Irbesartan is 99.80%；Other fingers
Mark meets regulation.
The Dissolution experiments of the Irbesartan Tablets of embodiment 6
Tested more than and determine that the dissolution test method of this product is as follows：
The medicine of Example 1,2,3, according to dissolution method (《Chinese Pharmacopoeia》The two annex X C second of version in 2010
Method), using 0.1mol/L hydrochloric acid solutions 900ml as dissolution medium, rotating speed is 50 turns per minute, is operated in accordance with the law, during through 20 minutes, is taken
Solution 10ml, filtration, precision measure that subsequent filtrate is appropriate, are quantitatively diluted and be made in every 1ml containing about 10 μ g solution with dissolution medium,
According to UV-VIS spectrophotometry (two A of annex IV of Chinese Pharmacopoeia version in 2010), absorbance is determined at 245nm wavelength；Separately
Take Irbesartan reference substance appropriate, it is accurately weighed, add dissolution medium to dissolve and quantify dilution be made it is molten containing about 10 μ g in every 1ml
Liquid, it is measured in the same method, calculates the stripping quantity of every.Limit is the 80% of labelled amount, should meet regulation.It is shown in Table 10.
Table every dissolution rate of 10 3 batches of Irbesartan Tablets
Interpretation of result：Irbesartan dissolution rate in embodiment 1,2,3 three batches of Irbesartan Tablets every meets regulation.
The average dissolution rate of Irbesartan in three batches of Irbesartan Tablets is shown in Table 11.
11 3 batches of Irbesartan Tablets dissolution rates of table
Interpretation of result：Irbesartan dissolution rate in embodiment 1,2,3 three batches of Irbesartan Tablets meets regulation.
The long-term stable experiment of the Irbesartan Tablets of embodiment 7
The Irbesartan Tablets of embodiment 1 are subjected to long-term stable experiment under storage requirement as defined in listing, investigate strategic point
Bei Shatan pieces in transport, preserve, the stability features during use, so as to as the determination term of validity and storage requirement according to
According to.By using the Irbesartan Tablets of polyvinyl chloride/low density polyethylene (LDPE) solid medicinal composite hard sheet, Key works Drug packing In Aluminium Foil Packing
Sample, be positioned over 25 DEG C ± 2 DEG C, place 24 months in the constant temperature of RH60% ± 10%, constant humidity cabinet, respectively at 0,3,6,9,12,
18th, sample within 24 months, detect every quality index.It the results are shown in Table 12.
The long term test of the Irbesartan Tablets of table 12
As a result：Through the long-time stability investigation of 24 months, as a result show that indices are without significant change, table compared with 0 month
Bright Irbesartan Tablets have good stability under the conditions of 25 DEG C ± 2 DEG C, RH60% ± 10%, produced under defined terms and conditions,
Packaging, storage, transport will not have a negative impact to the quality of this product, can ensure that clinical application is safe and effective.
Claims (9)
1. a kind of Irbesartan Tablets, it is characterised in that be made up of following raw material by mass parts：
Described Irbesartan Tablets are prepared as follows：
(1) Irbesartan, sucrose, montmorillonite are crushed into sieving for standby；
(2) 95%w/w medicinal alcohol is added into purified water and is configured to 75~80%w/w ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then add ethanol water made from step (2)
Solution, it is uniformly mixed and softwood is made, sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried, sieving whole grain obtains dry particl, standby；
(5) addition magnesium stearate, silica are well mixed with dry particl made from step (4), and tabletting produces.
2. Irbesartan Tablets as claimed in claim 1, it is characterised in that be made up of following raw material by mass parts：
3. Irbesartan Tablets as claimed in claim 2, it is characterised in that be made up of following raw material by mass parts：
4. Irbesartan Tablets as claimed in claim 2, it is characterised in that be made up of following raw material by mass parts：
5. Irbesartan Tablets as claimed in claim 2, it is characterised in that be made up of following raw material by mass parts：
6. the Irbesartan Tablets as described in claim any one of 1-5, it is characterised in that medicine piece is 0.25~0.30g/ again
Piece.
7. the preparation method of the Irbesartan Tablets as described in claim any one of 1-5, comprises the following steps；
(1) Irbesartan, sucrose, montmorillonite are crushed into sieving for standby；
(2) 95%w/w medicinal alcohol is added into purified water and is configured to 75~80%w/w ethanol waters, it is standby；
(3) Irbesartan, sucrose, montmorillonite are weighed according to proportioning, be well mixed, then add ethanol water made from step (2)
Solution, it is uniformly mixed and softwood is made, sieves and wet granular is made；
(4) wet granular prepared by step (3) is dried, sieving whole grain obtains dry particl, standby；
(5) addition magnesium stearate, silica are well mixed with dry particl made from step (4), and tabletting produces.
8. the preparation method of Irbesartan Tablets as claimed in claim 7, it is characterised in that the E Beisha described in step (1)
It is smooth, cross 80~100 mesh sieves；Described sucrose, cross 110~130 mesh sieves；Described montmorillonite, cross 350~400 mesh sieves.
9. the preparation method of Irbesartan Tablets as claimed in claim 7, it is characterised in that drying described in step (4) be
Dried 1~4 hour under the conditions of 45~60 DEG C；The sieving whole grain was 16~24 mesh sieves；The moisture of described dry particl is 3%
Below w/w.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2065035A1 (en) * | 2007-11-28 | 2009-06-03 | Laboratorios Lesvi, S.L. | Pharmaceutical formulations containing irbesartan |
| CN101632644A (en) * | 2008-07-25 | 2010-01-27 | 北京以岭生物工程有限公司 | Avapro dispersible tablet and preparation method thereof |
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| US20090030052A1 (en) * | 2006-02-17 | 2009-01-29 | Alembic Limited | Pharmaceutical tablet compositions containing irbesartan |
| KR20090052944A (en) * | 2007-11-22 | 2009-05-27 | 문영일 | A pharmaceutical composition comprising irbesartan |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2065035A1 (en) * | 2007-11-28 | 2009-06-03 | Laboratorios Lesvi, S.L. | Pharmaceutical formulations containing irbesartan |
| CN101632644A (en) * | 2008-07-25 | 2010-01-27 | 北京以岭生物工程有限公司 | Avapro dispersible tablet and preparation method thereof |
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