CN105078913A - Irbesartan tablet and preparation method thereof - Google Patents
Irbesartan tablet and preparation method thereof Download PDFInfo
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- CN105078913A CN105078913A CN201410220124.0A CN201410220124A CN105078913A CN 105078913 A CN105078913 A CN 105078913A CN 201410220124 A CN201410220124 A CN 201410220124A CN 105078913 A CN105078913 A CN 105078913A
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Abstract
The invention relates to an irbesartan tablet and a preparation method thereof. The irbesartan tablet is prepared from the following raw materials in parts by mass: 150-450 parts of irbesartan, 15-50 parts of montmorillonite, 85-270 parts of sucrose, 0.5-1.5 parts of magnesium stearate and 0.5-1.5 parts of silicon dioxide. The invention also provides a preparation method of the irbesartan tablet. The irbesartan tablet disclosed by the invention, by matching special accessories and main drugs and through special proportions, can be used for solving the problems of existing drug particles which are poor in liquidity, non-ideal in drug disintegration, low in drug dissolution, poor in stability, not high in bioavailability in human body and the like.
Description
Technical field
The present invention relates to a kind of Irbesartan Tablets and preparation method thereof, belong to medical art.
Background technology
According to the ill statistics of Chinese hypertension in 2002, current China adult hypertension prevalence reached 18.8%, national hypertension total number of persons nearly 1.6 hundred million.Because of the various complication that hypertension causes, it is the major reason causing cerebrovascular disease death.Therefore, how effectively to prevent and treat hypertension, reduce or reduce the various complication caused by hypertension, be improve China's population quality, reduce the important measures of mortality of cardio and cerebral vascular disease.
Irbesartan Tablets is angiotensinⅡ (Angiotensin II, Ang II) acceptor inhibitor, Ang I can be suppressed to be converted into Ang II, can antagonizing angiotensin converting Enzyme 1 receptor (AT1) specifically, AT28500 is greater than doubly to the antagonism of AT1, by optionally blocking Ang II and the combination of AT1 receptor, suppressing the release of vasoconstriction and aldosterone, producing hypotensive effect.This product does not suppress Angiotensin-Converting (ACE), feritin, other hormone receptor, does not suppress the ion channel relevant with blood pressure regulating and sodium balance yet.
China's hypertension drug market potential is huge, because the living standard of people improves, and work competition growing tension, Hypertension number increases greatly, especially in economy developing northern the greater part gradually, Hypertensive Population will expand, and depressor has the larger market demand.
Though current China pharmaceutical market is still occupied an leading position with calcium antagonist and ACEI, ACEI increases very fast, although to the location of the definite indication of sartans (single dose and compound preparation), be only limited to hypertension at present, accumulation is waited to the clinical data of other indications, but there is excellent antihypertensive effect due to the smooth class of sand, the side reactions such as dry cough are low, the compliance of patient is good, and the Clinical practice basis of existing several years, has certain popularity in hospital doctor.Losartan ELITE-2 result of the test makes husky smooth kind new medicine be subject to major defeat, mean the loss of market of such medicine in heart failure treatment, but brand-new Hypotensive Mechanism makes sartans have good market point of penetration (as: steady blood pressure lowering, side reaction low, without dry cough acceptor levels suppression etc.).
Chinese patent document CN103191076A discloses a kind of irbesartan tablet preparation method, is dissolved in by irbesartan in sodium hydrate aqueous solution, dry and pharmaceutic adjuvant mixed pressuring plate after adding polyvinylpolypyrrolidone absorption; Its object of the method is in order to solve the dissolution of medicine, and irbesartan is dissolved in sodium hydroxide solution by the method, has changed the physicochemical property of medicine, and creates new material, may bring other unknown effects clinically.
Chinese patent document CN102309456B discloses a kind of Irbesartan sodium micro composite powder and tablet and preparation method thereof, it adopts and is dissolved in organic solvent by irbesartan, add pharmaceutic adjuvant mix homogeneously, carry out spraying dry, prepare amorphous and crystal type Irbesartan sodium micro composite powder, with tabletting after mix lubricant, the method its objective is the dissolution in order to solve medicine, but owing to passing through high temperature spray-drying method, may make medicine and adjuvant in hot environment, cause unstability factor, make the preparation related substance of irbesartan against regulation.
Because irbesartan is non-solubization medicine, and existing formulation disintegrates is slow, and adopts routine prescription and conventional fabrication process and adjuvant, is difficult to solve the technical barrier that bioavailability in drug dissolution and human body is lower.Therefore find a kind of steady quality, safe and effective irbesartan tablet recipe and adjuvant and preparation technology become matter of utmost importance.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of Irbesartan Tablets and preparation method thereof.By coordinating of specific adjuvant and principal agent, and specific proportioning, solve that existing drug particles mobility is bad, medicine disintegration is undesirable, drug dissolution is low, poor stability and the problem such as human bioavailability is not high.
Technical scheme of the present invention is as follows:
A kind of Irbesartan Tablets, be made up by mass parts of following raw material:
According to the present invention, preferably,
A kind of Irbesartan Tablets, be made up by mass parts of following raw material:
According to the present invention, further preferably,
A kind of Irbesartan Tablets, be made up by mass parts of following raw material:
Or, a kind of Irbesartan Tablets, be made up by mass parts of following raw material:
Or, a kind of Irbesartan Tablets, be made up by mass parts of following raw material:
Irbesartan Tablets of the present invention, wherein said Montmorillonitum is medicinal smectite.What raw material used in the present invention was not specified is conventional commercial products.
The preparation method of Irbesartan Tablets of the present invention, comprises the following steps:
(1) irbesartan, sucrose, Montmorillonitum are pulverized sieving for standby;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add the ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet grain drying prepared by step (3), the granulate that sieves must do granule, for subsequent use;
(5) the dry granule adding magnesium stearate, silicon dioxide and step (4) obtained is mixed homogeneously, tabletting and get final product.
According to the present invention, preferably,
Irbesartan described in step (1), crosses 80 ~ 100 mesh sieves; Described sucrose, crosses 110 ~ 130 mesh sieves; Described Montmorillonitum, crosses 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 under 45 ~ 60 DEG C of conditions dry 1 ~ 4 hour; The described granulate that sieves was 16 ~ 24 mesh sieves; The moisture of described dry granule be 3% (w/w) below.
Described Irbesartan Tablets medicine sheet is heavily 0.25 ~ 0.30g/ sheet.
Irbesartan Tablets of the present invention safety, efficient, quality controllable, easy to use, this sheet compared with existing irbesartan medicine, no matter be formula or have significant distinctive feature in preparation method.Be specially:
1, Irbesartan Tablets pharmaceutical formulation application Montmorillonitum of the present invention is disintegrating agent, and make the kind and the use amount that significantly reduce adjuvant in Irbesartan Tablets, disintegration time and dissolution rate significantly improve, and Irbesartan Tablets good stability, simple process.
2, add filler sucrose in the present invention, wherein namely sucrose play filler effect in Irbesartan Tablets, plays again binding agent effect, wherein works in coordination with Montmorillonitum peptizaiton further adding of sucrose, promote the disintegration rate of Irbesartan Tablets.
In sum, the invention provides a kind of can the Irbesartan Tablets medicine of disintegrate rapidly, drastically increase disintegration rate, dissolution is high; Guaranteeing make its therapeutic efficiency unaffected under Irbesartan Tablets medicine meets the prerequisite of quality standard and improve human bioavailability simultaneously, there is great strategic structural, good market prospects.
Below in conjunction with experimental example, the present invention is described further, but be not limited thereto.
Experimental example 1: the screening experiment of disintegrating agent
In the present invention, the kind of disintegrating agent and the dissolution of Irbesartan Tablets and bioavailability closely related.At present, in preparation research process, the most frequently used disintegrating agent has: nearly 20 kinds of carboxymethyl starch sodium (CMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crospolyvinylpyrrolidone (PVPP) etc., disintegrating agent in tablet self has stronger water swellability mostly, thus disintegrates the adhesion of tablet.Usually said high-quality disintegrating agent refers to that water absorption and swelling degree is greater than the disintegrating agent of 5ml/g, and expansion rate is larger, and disintegrate effect is more remarkable.The selection of disintegrating agent is one of factor important in tablet formulation design, the disintegrating agent of research and development function admirable, or select suitable disintegrating agent and improvement preparation technology according to the characteristic of different disintegrating agents, the tablet of development will be made to have more excellent Release Performance.
1, to the imbibition degree research experiment of Montmorillonitum and carboxymethyl starch sodium (CMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crospolyvinylpyrrolidone (PVPP), pregelatinized Starch; In table 1.
Weight and volume number after table 11g sample fully absorbs water
| Disintegrating agent | 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 |
| Carboxymethyl starch sodium (CMS-Na) | 19.29±0.21 | 20.4±0.3 |
| Crospolyvinylpyrrolidone (PVPP) | 4.04±0.13 | 5.6±0.2 |
| Montmorillonitum | 18.78±0.24 | 19.8±0.3 |
Comparatively large by the swelling volume that can analyze Montmorillonitum in table 1, be 19.8ml/g; Be slightly smaller than carboxymethyl starch sodium (CMS-Na), be greater than other disintegrating agent.
2, the comparative study of the disintegrating property of Montmorillonitum and conventional disintegrating agent; The present invention adopts calcium carbonate to prepare blank model sheet, with the hardness of tablet and disintegration for inspection target, and the disintegrating property research experiment to Montmorillonitum: in table 2.
Several disintegrating agent hardness of table 2 and disintegration time compare
| Disintegrating agent | Hardness (N) | Disintegration time (minute) |
| Calcium carbonate (blank model sheet) | 57 | > 2 hours |
| Low-substituted hydroxypropyl cellulose (L-HPC) | 51 | 4.32±1.11 |
| Pregelatinized Starch | 49 | 6.16±0.83 |
| Carboxymethyl starch sodium (CMS-Na) | 56 | 3.16±0.64 |
| Crospolyvinylpyrrolidone (PVPP) | 56 | 2.02±0.87 |
| Montmorillonitum | 54 | 2.23±0.96 |
Analyzed by table 2, when hardness close to, time not with disintegrating agent, the disintegration time of the blank model sheet of calcium carbonate is more than two hours, add the tablet of disintegrating agent, disintegration time obviously shortens, and wherein crospolyvinylpyrrolidone (PVPP) disintegration time is the shortest, and Montmorillonitum is better than other disintegrating agent.
By table 1,2 test and studies, the present invention selects Montmorillonitum to be the disintegrating agent of Irbesartan Tablets.
Experimental example 2: prescription screening is tested
This tablet the adjuvant intended be pharmaceutic adjuvant grade, for this preparation characteristic and in conjunction with tablet R&D experience, the prescription of Design Fundamentals screening.Respectively character, friability, disintegration time, dissolution are investigated, and note observing preparation process phenomenon.In table 3.
Table 3 Irbesartan Tablets prescription screening 1 (unit: g)
| Component | 01 | 02 | 03 |
| Irbesartan | 150 | 150 | 150 |
| Montmorillonitum | 3 | 6 | 9 |
| Sucrose | 98 | 98 | 98 |
| Magnesium stearate | 0.5 | 0.5 | 0.5 |
| Silicon dioxide | 0.5 | 0.5 | 0.5 |
Method for making: preparation 75% (w/w) alcoholic solution;
Get supplementary material irbesartan, sucrose, Montmorillonitum, mix homogeneously, add binding agent ethanol water and prepare soft material, cross 20 mesh sieves and obtain wet granular;
Wet granular is dried under 50 ± 5 DEG C of conditions, 16 mesh sieve granulate;
Add magnesium stearate lubricant, silicon dioxide mix homogeneously;
With the stamping of 9mm dimple form circle.
Each prescription is tested, the results are shown in following table 4:
Table 4 prescription screening tests 1 assay
| Supplementary material | 01 | 02 | 03 |
| Character | Unilateral not bright and clean | Unilateral bright and clean | Unilateral bright and clean |
| Friability | Conform with the regulations | Conform with the regulations | Conform with the regulations |
| Disintegration time (min) | 30 | 26 | 17 |
| Remarks | Compressibility is very poor, cannot tabletting | Mobility of particle is poor, the heavy more difficult control of sheet | Disintegration time is longer |
Interpretation of result: prescription 1 granule compressibility is too poor, easy sticking causes cannot normal tabletting, and disintegration time is longer, abandons.Prescription 2 mobility of particle is poor, and uncontrollable weight, another disintegration time is oversize, abandons.Prescription 3 preparation process is comparatively smooth, but tablet disintegration times is longer, can affect subsequent product dissolution determination, therefore adjusts supplementary product kind, consumption according to prescription 3, continues screening prescription.In table 5.
Table 5 prescription screening 2 (unit: g)
| Component | 04 | 05 | 06 |
| Irbesartan | 150 | 150 | 150 |
| Montmorillonitum | 12 | 14 | 16 |
| Sucrose | 98 | 98 | 98 |
| Magnesium stearate | 0.5 | 0.5 | 0.5 |
| Silicon dioxide | 0.5 | 0.5 | 0.5 |
Method for making: preparation 80% (w/w) alcoholic solution;
Get supplementary material irbesartan, sucrose, Montmorillonitum, mix homogeneously, add binding agent ethanol water and prepare soft material, cross 20 mesh sieves and obtain wet granular;
Wet granular is dried under 50 ± 5 DEG C of conditions, 16 mesh sieve granulate;
Add magnesium stearate lubricant, silicon dioxide mix homogeneously;
With the stamping of 9mm dimple form circle.
Each prescription is tested, the results are shown in following table 6:
Table 6 prescription screening tests 2 assays
| Supplementary material | 04 | 05 | 06 |
| Character | Unilateral bright and clean | Unilateral bright and clean | Unilateral bright and clean |
| Friability | Conform with the regulations | Conform with the regulations | Conform with the regulations |
| Disintegration time | 12 | 10 | 6 |
| Dissolution | 31.4 | 73.40 | 95.50 |
| Content | 99.27 | 100.12 | 99.80 |
| Remarks | Disintegration time is longer, stripping is very poor | Stripping is lower | Well |
Conclusion: prescription 4 tablet disintegration times is longer, stripping is too low, abandons.The stripping of prescription 5 tablet is lower, defective, abandons.Prescription 6 gained tablet is every all good.So determine that prescription 6 is the optimum prescription of this preparation.
Experimental example 3: supplementary material compatibility experiments
The Montmorillonitum selected in Irbesartan Tablets drug research process of the present invention is as disintegrating agent, and sucrose is as filler, and supplementary material compatibility test is as follows;
By raw material and selected adjuvant physical mixed by a certain percentage, according to the experimental technique of influence factor in Chinese Pharmacopoeia 2010 editions two (annex Ⅺ Ⅹ C) crude drug and pharmaceutical preparation stability test guideline, place 10 days under the condition of high temperature 60 DEG C ± 2 DEG C, humidity 90% ± 5%, high light 4500 ± 500lx respectively, check change before and after placing.Result of the test is as follows:
1, hot conditions supplementary material compatibility test
Mixed according to a certain percentage by supplementary material, expose and set high lower 10 days of temperature 60 DEG C ± 2 DEG C conditions, respectively at sampling in 0,5,10 day, assay was shown in lower 7 tables.
Table 7 supplementary material compatibility test 10 days
Through high temperature 60 DEG C ± 2 DEG C conditions lower 10 days compatibility tests, result shows each adjuvant character, related substance, content are all unchanged.The display of moisture check result extends in time and reduces.
Above result shows that irbesartan is good with the adjuvant compatibility under high temperature 60 DEG C ± 2 DEG C conditions.
2, super-humid conditions supplementary material compatibility test
Supplementary material is mixed according to a certain percentage, exposes and set high lower 10 days of wet (90% ± 5%) condition, respectively at sampling in 0,5,10 day, measure indices, the results are shown in 8 tables.
Sample is divided equally three parts and is carried out three condition tests after weighing, therefore high humidity 10 days results were with high temperature 10 days.
Table 8 supplementary material compatibility test high humidity (90% ± 5%) 10 days
Through high humidity 90% ± 5% condition lower 10 days compatibility tests, result shows each adjuvant character, related substance, content are all unchanged.Because this law is under material is exposed to super-humid conditions, therefore some projects moisture increases to some extent.
Above result shows that irbesartan is good with the adjuvant compatibility under high humidity 90% ± 5% condition.Composite score shows that preparation should seal preservation.
3, illumination condition supplementary material compatibility test
Supplementary material is mixed according to a certain percentage, exposes and put illumination (4500 ± 500lx) condition lower 10 days, respectively at sampling in 0,5,10 day, measure irbesartan content and compared with 0 day, the results are shown in Table 9.
Illumination 0 day result was with high temperature 0 day.
Table 9 supplementary material compatibility test illumination (4500 ± 500lx) 10 days
Through illumination (4500 ± 500lx) condition lower 10 days compatibility tests, result shows each adjuvant character, related substance, content are all unchanged, and Yin Benfa is under material exposure condition, therefore some projects moisture increases to some extent
Above result shows that irbesartan is good with the adjuvant compatibility under illumination (4500 ± 500lx) condition.
Under supplementary material compatibility test shows three kinds of experimental conditions, the every leading indicator of all samples and raw material ratio comparatively have no significant change, and show that irbesartan and above-mentioned adjuvant all have the better compatibility, selected adjuvant is reasonable.
To sum up experimental result shows: the disintegrating agent in Irbesartan Tablets medicine of the present invention adopts Montmorillonitum; The sucrose that filler adopts, wherein sucrose draws moist stronger, and the water swellability of Montmorillonitum in water is 19.8ml/g, the synergism of these two kinds of adjuvants, thus make Irbesartan Tablets dispersion of medicine good, dissolution is high, and simple process, industrialization degree is high, and adjuvant uses few, and production cost is low.
Accompanying drawing explanation
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.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described further, but be not limited thereto.
In embodiment, supplementary material source is described as follows:
| Supplementary material title | Manufacturing enterprise | Operative norm |
| Irbesartan | Xiuzheng Pharmaceutical Group Liuhe Pharmaceutical Co., Ltd. | National drug standards WS1-(X-005)-2005Z |
| Montmorillonitum | Shandong Xian He pharmaceutical Co. Ltd | Chinese Pharmacopoeia 2010 editions addendums |
| Sucrose | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Magnesium stearate | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Silicon dioxide | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Medicinal alcohol (95%) | Hu'nan Erkang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Purified water | Shandong Sibangde Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
Device involved in embodiment and equipment are solid preparation and produce common apparatus, and market can be purchased.Be described as follows:
Universal high-efficiency pulverizer (model 30B), square shaking screen (model FS-0.5M2-X), high-speed mixing granulating machine (model 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 company limited is on sale.
Full-automatic two discharging high speed tablet press (model GZPS-49): Beijing Hanlin Hangyu Technology Development Co., Ltd. is on sale.
Embodiment 1: the preparation of Irbesartan Tablets
Irbesartan Tablets, be made up by mass parts of following raw material:
Preparation method is as follows:
(1) by irbesartan, sucrose, Montmorillonitum, pulverize; Wherein to cross 90 mesh sieves for subsequent use for irbesartan; It is for subsequent use that 120 mesh sieves crossed by sucrose; It is for subsequent use that 350 mesh sieves crossed by Montmorillonitum;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add 75 ~ 80% (w/w) ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet granular prepared by step (3) 50 ~ 52 DEG C of dryings 1.5 hours, detect pellet moisture 2.5%, cross 25 mesh sieve granulate, for subsequent use;
(5) the dry granule adding metering part magnesium stearate, silicon dioxide obtained with step (4) is mixed homogeneously, and granule 9mm dimple form is justified stamping and namely obtained Irbesartan Tablets.
Testing result:
Outward appearance flap-type is complete, smooth, dispersing uniformity conforms with the regulations, (related substance (1), (2), (3) refer to that irbesartan has three related substances to irbesartan related substance for (1) 0.12%, (2) 0.13%, (3) 0.25, usual use 1,2,3 is stated), the Irbesartan Tablets dissolution of 30 minutes is 99.23%.The content of irbesartan is 99.53%, and other index all conforms with the regulations.
The preparation of embodiment 2 Irbesartan Tablets:
Irbesartan Tablets, be made up by mass parts of following raw material:
Preparation method is as follows:
(1) by irbesartan, sucrose, Montmorillonitum, pulverize; Wherein to cross 80 mesh sieves for subsequent use for irbesartan; It is for subsequent use that 110 mesh sieves crossed by sucrose; It is for subsequent use that 400 mesh sieves crossed by Montmorillonitum;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add 75 ~ 80% (w/w) ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet granular prepared by step (3) 53 ~ 55 DEG C of dryings 1 hour, detect pellet moisture 2.3%, cross 30 mesh sieve granulate, for subsequent use;
(5) the dry granule adding metering part magnesium stearate, silicon dioxide obtained with step (4) is mixed homogeneously, and granule 9mm dimple form is justified stamping and namely obtained Irbesartan Tablets.
Testing result:
Outward appearance flap-type is complete, smooth, and dispersing uniformity conforms with the regulations, and irbesartan related substance is (1) 0.11%, (2) 0.12% (3) 0.26, and the irbesartan dissolution of 30 minutes is 98.39%.The content of irbesartan is 99.6%, and other index all conforms with the regulations.
The preparation of embodiment 3 Irbesartan Tablets:
Irbesartan Tablets, be made up by mass parts of following raw material:
Preparation method is as follows:
(1) by irbesartan, sucrose, Montmorillonitum, pulverize; Wherein to cross 80 mesh sieves for subsequent use for irbesartan; It is for subsequent use that 130 mesh sieves crossed by sucrose; It is for subsequent use that 370 mesh sieves crossed by Montmorillonitum;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add 75 ~ 80% (w/w) ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet granular prepared by step (3) 52 ~ 54 DEG C of dryings 1.2 hours, detect pellet moisture 2.15%, cross 40 mesh sieve granulate, for subsequent use;
(5) the dry granule adding metering part magnesium stearate, silicon dioxide obtained with step (4) is mixed homogeneously, and granule 9mm dimple form is justified stamping and namely obtained Irbesartan Tablets.
Testing result:
Outward appearance flap-type is complete, smooth, and dispersing uniformity conforms with the regulations, and irbesartan related substance is (1) 0.13%, (2) 0.11% (3) 0.27, and the irbesartan dissolution of 30 minutes is 97.14%.The content of irbesartan is 100.01%; Other index all conforms with the regulations.
The preparation of embodiment 4 Irbesartan Tablets:
Irbesartan Tablets, be made up by mass parts of following raw material:
Preparation method is as follows:
(1) by irbesartan, sucrose, Montmorillonitum, pulverize; Wherein to cross 100 mesh sieves for subsequent use for irbesartan; It is for subsequent use that 120 mesh sieves crossed by sucrose; It is for subsequent use that 350 mesh sieves crossed by Montmorillonitum;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add 75 ~ 80% (w/w) ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet granular prepared by step (3) 55 ~ 57 DEG C of dryings 2 hours, detect pellet moisture 2.35%, cross 20 mesh sieve granulate, for subsequent use;
(5) the dry granule adding metering part magnesium stearate, silicon dioxide obtained with step (4) is mixed homogeneously, and granule 9mm dimple form is justified stamping and namely obtained Irbesartan Tablets.
Testing result:
Outward appearance flap-type is complete, smooth, and dispersing uniformity conforms with the regulations, and irbesartan related substance is (1) 0.13%, (2) 0.12% (3) 0.26, and the irbesartan dissolution of 30 minutes is 96.70%.The content of irbesartan is 99.70%; Other index all conforms with the regulations.
The preparation of embodiment 5 Irbesartan Tablets:
Irbesartan Tablets, be made up by mass parts of following raw material:
Preparation method is as follows:
(1) by irbesartan, sucrose, Montmorillonitum, pulverize; Wherein to cross 80 mesh sieves for subsequent use for irbesartan; It is for subsequent use that 110 mesh sieves crossed by sucrose; It is for subsequent use that 350 mesh sieves crossed by Montmorillonitum;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add 75 ~ 80% (w/w) ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet granular prepared by step (3) 53 ~ 55 DEG C of dryings 1 hour, detect pellet moisture 2.3%, cross 30 mesh sieve granulate, for subsequent use;
(5) the dry granule adding metering part magnesium stearate, silicon dioxide obtained with step (4) is mixed homogeneously, and granule 9mm dimple form is justified stamping and namely obtained Irbesartan Tablets.
Testing result:
Outward appearance flap-type is complete, smooth, and dispersing uniformity conforms with the regulations, and irbesartan related substance is (1) 0.12%, (2) 0.11% (3) 0.25, and the irbesartan dissolution of 30 minutes is 98.70%.The content of irbesartan is 99.80%; Other index all conforms with the regulations.
The Dissolution experiments of embodiment 6 Irbesartan Tablets
Determine that the dissolution test method of this product is as follows through above test:
The medicine of Example 1,2,3, according to dissolution method (" Chinese Pharmacopoeia " version in 2010 two annex XC second methods), with 0.1mol/L hydrochloric acid solution 900ml for dissolution medium, rotating speed is 50 turns per minute, operate in accordance with the law, through 20 minutes time, get solution 10ml, filter, it is appropriate that precision measures subsequent filtrate, quantitatively dilute the solution made about containing 10 μ g in every 1ml with dissolution medium, according to ultraviolet visible spectrophotometry (Chinese Pharmacopoeia version in 2010 two annex IV A), measure absorbance at 245nm wavelength place; Separately get irbesartan reference substance appropriate, accurately weighed, add stripping medium dissolves and quantitatively dilute the solution made about containing 10 μ g in every 1ml, being measured in the same method, calculating the stripping quantity of every sheet.Limit is 80% of labelled amount, should conform with the regulations.In table 10.
The every sheet dissolution of table 10 three batches of Irbesartan Tablets
Interpretation of result: the irbesartan dissolution in embodiment 1,2,3 three batches of every sheets of Irbesartan Tablets all conforms with the regulations.
The average dissolution of irbesartan in three batches of Irbesartan Tablets is in table 11.
Table 11 three batches of Irbesartan Tablets dissolutions
Interpretation of result: the irbesartan dissolution in embodiment 1,2,3 three batches of Irbesartan Tablets all conforms with the regulations.
The long-term stable experiment of embodiment 7 Irbesartan Tablets
The Irbesartan Tablets of embodiment 1 is carried out long-term stable experiment under the storage requirement of listing regulation, investigates the stability features of Irbesartan Tablets in transport, preservation, use procedure, thus as determining the foundation of effect duration and storage requirement.The Irbesartan Tablets sample of polrvinyl chloride/Low Density Polyethylene solid medicinal composite hard sheet, drug packaging In Aluminium Foil Packing will be adopted, be positioned over 25 DEG C ± 2 DEG C, the constant temperature of RH60% ± 10%, place 24 months in constant humidity cabinet, respectively at sampling in 0,3,6,9,12,18,24 month, detect every quality index.The results are shown in Table 12.
The long term test of table 12 Irbesartan Tablets
Result: through the long-time stability investigation of 24 months, result display compared indices without significant change with 0 month, show Irbesartan Tablets 25 DEG C ± 2 DEG C, RH60% ± 10% condition stability inferior is good, under the terms and conditions of regulation, production, packaging, storage, transport all can not have a negative impact to the quality of this product, can ensure that clinical drug safety is effective.
Claims (10)
1. an Irbesartan Tablets, is characterized in that, is made up by mass parts of following raw material:
2. Irbesartan Tablets as claimed in claim 1, is characterized in that, be made up of following raw material by mass parts:
3. Irbesartan Tablets as claimed in claim 1 or 2, is characterized in that, be made up of following raw material by mass parts:
4. Irbesartan Tablets as claimed in claim 1 or 2, is characterized in that, be made up of following raw material by mass parts:
5. Irbesartan Tablets as claimed in claim 1 or 2, is characterized in that, be made up of following raw material by mass parts:
6. the Irbesartan Tablets as described in any one of claim 1-5, is characterized in that, medicine sheet is heavily 0.25 ~ 0.30g/ sheet.
7. the preparation method of the Irbesartan Tablets as described in any one of claim 1-5, comprises the following steps;
(1) irbesartan, sucrose, Montmorillonitum are pulverized sieving for standby;
(2) medicinal alcohol of 95% (w/w) is added purified water and be mixed with 75 ~ 80% (w/w) ethanol water, for subsequent use;
(3) take irbesartan, sucrose, Montmorillonitum according to proportioning, mix homogeneously, then add the ethanol water that step (2) is obtained, be uniformly mixed and make soft material, sieve obtained wet granular;
(4) by the wet grain drying prepared by step (3), the granulate that sieves must do granule, for subsequent use;
(5) the dry granule adding magnesium stearate, silicon dioxide and step (4) obtained is mixed homogeneously, tabletting and get final product.
8. the preparation method of Irbesartan Tablets as claimed in claim 7, is characterized in that, the irbesartan described in step (1), crosses 80 ~ 100 mesh sieves; Described sucrose, crosses 110 ~ 130 mesh sieves; Described Montmorillonitum, crosses 350 ~ 400 mesh sieves.
9. the preparation method of Irbesartan Tablets as claimed in claim 7, it is characterized in that, the addition of ethanol water described in step (3) is 5 ~ 10% (w/w) of total solid substance.
10. the preparation method of Irbesartan Tablets as claimed in claim 7, is characterized in that, drying described in step (4) is under 45 ~ 60 DEG C of conditions dry 1 ~ 4 hour; The described granulate that sieves was 16 ~ 24 mesh sieves; The moisture of described dry granule be 3% (w/w) below.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111249248A (en) * | 2020-02-03 | 2020-06-09 | 北京阳光诺和药物研究有限公司 | Blood lipid reducing medicine 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 |
| 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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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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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| CN111249248A (en) * | 2020-02-03 | 2020-06-09 | 北京阳光诺和药物研究有限公司 | Blood lipid reducing medicine and preparation method thereof |
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