CN103989646A - Irbesartan medicinal composition, as well preparation method and application thereof - Google Patents
Irbesartan medicinal composition, as well preparation method and application thereof Download PDFInfo
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- CN103989646A CN103989646A CN201410233928.4A CN201410233928A CN103989646A CN 103989646 A CN103989646 A CN 103989646A CN 201410233928 A CN201410233928 A CN 201410233928A CN 103989646 A CN103989646 A CN 103989646A
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Abstract
The invention relates to an irbesartan medicinal composition, as well as a preparation method and application thereof. The preparation method comprises the following steps: preparing irbesartan solid dispersion which is prepared from irbesartan and a carrier material by adopting hot-melt granulation of a hot-melt extrusion granulator or a spray type solid dispersing agent preparation machine; mixing the irbesartan solid dispersion with a proper amount of diluting agent, disintegrating agent, surfactant, adhesive, flow aid and lubriant into tablets. According to the preparation method, irbessartan is prepared into a solid dispersing agent body and further prepared into a tablet, so that the dissolution rate is improved, and good absorption and biological utilization are achieved.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to pharmaceutical composition of irbesartan and its production and use.
Background technology
Cardiovascular disease is the disease of a class serious harm human body health, raising day by day along with social progress and human living standard, the sickness rate of this class disease rises gradually, become the No.1 killer of human health, hypertension is the most commonly encountered diseases in cardiovascular disease, its sickness rate is more and more high, and there is the trend of rejuvenation, therefore antihypertensive pharmaceutical requirements amount is very huge, and exploitation is efficient, long-acting, height cardiovascular selectivity, many organ protections, can belong to the task of top priority by concurrent various metabolism disorders and the little depressor of side effect of correcting blood pressure, irbesartan is the blood pressure lowering good medicine that meets these conditions.
Irbesartan is angiotensin-ii receptor 1 (AT1) selective antagonist of a kind of oral, non-polypeptide class, high selectivity, Orally active is higher, it is a class newtype drug of clinical treatment cardiovascular disease, research shows: irbesartan 150mg can make the caused external pressure effect of exogenous Angiotensin II almost completely suppressed, to light, in, severe hypertension patient is all effective, and old people, hepatic and kidney function obstacle patient are not needed to adjust dosage.Compare with angiotensin converting enzyme inhibitor (ACE I), both are at different parts blocking-up feritin hypertensin system (RAS) and produce hypotensive effect one by one, irbesartan is similar to ACE I class medicine efficacy of antihypertensive treatment, but this product seldom causes the side effect of cough.
For most drug, oral administration is best route of administration, can improve patient compliance, and economy, safety.But many promising fat-soluble or poorly water soluble drugs cause bioavailability not good because of its poorly water-soluble, bioavailability is low is the main cause that pharmacological active substance can not become medicine.It is reported that about more than 40% new active substance is due to poorly water-soluble, preparation prescription and complex process, there is more problem in oral administration biaavailability.
It is the key factor that affects medicine inside and outside dependency that oral drugs absorb at gastrointestinal.In absorption process, the dissolution rate of medicine is generally the rate-limiting step of its absorption.Therefore, the dissolubility and the dissolution rate that improve insoluble drug often become the first step that improves its oral administration bioavailability, and traditional pharmaceutics solubilising means are conceived to this more.As select suitable crystal formation, and superfine grinding, salify, adds solubilizing agent, cosolvent etc.In addition, by changing the molecular structure of insoluble drug, selecting suitable carrier and preparation technique to improve its physicochemical property, improve itself and the affinity of gastrointestinal tract mucosa and permeability etc., is also the effective way of its oral absorption of promotion.
Irbesartan is a kind of insoluble drug, and bioavailability is low, can not directly make qualified oral formulations by crude drug.The oral absorption of medicine is a complicated physiological process, and influence factor is more, and with respect to other route of administration, oral administration has larger unpredictability.The oral administration of insoluble drug often due to absorption difference, bioavailability is low is restricted, development along with new technique, new material in pharmaceutical field, oneself is overcome this restriction gradually, and insoluble drug also can obtain good absorption and bioavailability by oral administration.
Solid dispersion technology is dispersed in insoluble drug in large hydrophilic molecular carrier, can make the particle diameter of medicine be reduced to molecular level, and this method is conducive to make solid preparation, preparation method is easy, adjuvant is cheap and easy to get, is conducive to industry and produces greatly and reduce production costs and clinical treatment expense.
Summary of the invention
Inventor is after large quantity research; wonderful discovery adopts hot-melt extruded granulator hot melt to granulate or aerosol type solid dispersion draft machine is made irbesartan solid dispersion by irbesartan and carrier material; again itself and appropriate diluent, disintegrating agent, surfactant, binding agent, fluidizer and mix lubricant are made to tablet; improve the dissolution of medicine, obtained good absorption and bioavailability.
On the one hand, the present invention relates to a kind of pharmaceutical composition of irbesartan, it comprises irbesartan solid dispersion 200-650 weight portion, diluent 60-180 weight portion, disintegrating agent 10-20 weight portion, surfactant 5-10 weight portion, binding agent 5-10 weight portion, fluidizer 3-8 weight portion, lubricant 1-6 weight portion, described irbesartan solid dispersion comprises irbesartan and carrier material, described carrier material is selected from Polyethylene Glycol, poloxamer, stearic acid, sodium stearate, glyceryl monostearate, Lac, in polyoxyethylene monostearate or glycerin gelatine one or more, the weight ratio of described irbesartan and carrier material is l:1～6.
In a preferred embodiment, the pharmaceutical composition of described irbesartan, it comprises irbesartan solid dispersion 400-450 weight portion, diluent 150-180 weight portion, disintegrating agent 15 weight portions, surfactant 6 weight portions, binding agent 6-8 weight portion, fluidizer 4-5 weight portion, lubricant 1.5 weight portions, described irbesartan solid dispersion forms by irbesartan with carrier material, described carrier material is selected from Polyethylene Glycol, poloxamer, stearic acid, sodium stearate, glyceryl monostearate, Lac, in polyoxyethylene monostearate or glycerin gelatine one or more, the weight ratio of described irbesartan and carrier material is l:1～2.
In another preferred embodiment, described Polyethylene Glycol is selected from PEG2000, PEG4000, PEG6000, in PEG8000 or 10000 one or more, described diluent is selected from lactose, in microcrystalline Cellulose or pre-paying starch one or more, described disintegrating agent is selected from carboxymethyl starch sodium or crospolyvinylpyrrolidone one or both, described surfactant is selected from sodium lauryl sulphate or polyoxyethylene sorbitan monoleate one or both, described binding agent is selected from polyvidone or hypromellose one or both, described fluidizer is selected from micropowder silica gel or silicon dioxide one or both, and described lubricant is magnesium stearate.
In another preferred embodiment, described irbesartan solid dispersion is to be prepared by hot-melt extruded granulator or aerosol type solid dispersion draft machine.
In another preferred embodiment, the pharmaceutical composition of described irbesartan is tablet form.
Second aspect, the present invention relates to a kind of method of preparing the pharmaceutical composition of irbesartan, and the method comprises the following steps:
1) irbesartan is mixed homogeneously with carrier material;
2) by hot-melt extruded granulator or aerosol type solid dispersion draft machine, said mixture is made to irbesartan solid dispersion;
3) irbesartan solid dispersion, diluent, disintegrating agent, surfactant, binding agent, fluidizer, lubricant were pulverized to 80-120 mesh sieve, then binding agent was dissolved in 30-60% alcoholic solution;
4) by step 3) irbesartan solid dispersion, diluent, disintegrating agent, the surfactant mix homogeneously of gained, add binder solution to granulate with 18-32 mesh sieve, 50-80 ℃ of oven dry, 24-40 mesh sieve granulate, then add fluidizer, mix lubricant even, obtain the pharmaceutical composition of described irbesartan.
In a preferred embodiment, the method is in step 4) further comprise afterwards tabletting step.
In another preferred embodiment, step 3) irbesartan solid dispersion, diluent, disintegrating agent, surfactant, binding agent, fluidizer, lubricant were pulverized to 100 mesh sieves, then binding agent is dissolved in 40% alcoholic solution.
In another preferred embodiment, step 4) by step 3) irbesartan solid dispersion, diluent, disintegrating agent, the surfactant mix homogeneously of gained, add binder solution to granulate with 20 mesh sieves, 60 ℃ of oven dry, 20-24 mesh sieve granulate, then add fluidizer, mix lubricant even, obtain the pharmaceutical composition of described irbesartan.
The third aspect, the pharmaceutical composition that the present invention relates to described irbesartan is treated the purposes in hypertensive medicine in preparation.
The invention still further relates to a kind of hypertensive method for the treatment of, it comprises the pharmaceutical composition of the irbesartan of the present invention that gives required patient treatment effective dose.
The invention still further relates to the pharmaceutical composition as the irbesartan of the present invention for the treatment of hypertension drug.
The specific embodiment
Embodiment 1:
Weigh PEG4000 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 94.12 ± 2.32%.(n＝6)
Embodiment 2:
Weigh PEG4000 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 6g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 20 mesh sieve granulate: add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 95.12 ± 2.12%.(n＝6)
Embodiment 3:
Weigh PEG4000 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external tired juice stripping percentage rate of Irbesartan Tablets 45min is 90.13 ± 2.02%.(n＝6)
Embodiment 4:
Weigh PEG4000 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 6g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 20 mesh sieve granulate; Add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 92.58 ± 2.52%.(n＝6)
Embodiment 5:
Weigh stearic acid 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves. take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 24 mesh sieve granulate: add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 83.12 ± 1.87%.(n＝6)
Embodiment 6:
Weigh stearic acid 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, taking 6g hypromellose is dissolved in appropriate 40% ethanol: take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC ten 40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 20 mesh sieve granulate; Add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 81.12 ± 2.37%.(n＝6)
Embodiment 7:
Weigh stearic acid 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, add hot melt in aerosol type solid dispersion draft machine to granulate, obtain irbesartan solid dispersion, shattered 100 mesh sieves: lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 82.92 ± 1.65%.(n＝6)
Embodiment 8:
Weigh stearic acid 200g, PEG6000 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 6g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 20 mesh sieve granulate; Add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 81.62 ± 2.02%.(n＝6)
Embodiment 9:
Weigh stearic acid 200g, poloxamer 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, add hot melt in hot-melt extruded granulator to granulate, obtain irbesartan solid dispersion, shattered 100 mesh sieves: lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 83.22 ± 1.98%.(n＝6)
Embodiment 10:
Weigh stearic acid 200g, poloxamer 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, add hot melt in hot-melt extruded granulator to granulate, obtain irbesartan solid dispersion, shattered 100 mesh sieves: by microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate was pulverized respectively 100 mesh sieves, taking 6g hypromellose is dissolved in appropriate 40% ethanol: take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 20 mesh sieve granulate, add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 81.05 ± 2.01%.(n＝6)
Embodiment 11:
Weigh stearic acid 200g, poloxamer 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, taking 8g polyvidone is dissolved in appropriate 40% ethanol: take respectively irbesartan solid dispersion 450g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 82.36+1.78%.(n＝6)
Embodiment 12:
Weigh stearic acid 200g, poloxamer 400g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, taking 6g hypromellose is dissolved in appropriate 40% ethanol: take respectively irbesartan solid dispersion 450g, microcrystalline Cellulose 70g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 62 mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, wet grain 60～C is dry, 20 mesh sieve granulate; Add 4g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 80.25 ± 2.11%.(n＝6)
Embodiment 13:
Weigh PEG4000 200g, PEG6000 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 400g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 90.06 ± 2.02%.(n＝6)
Embodiment 14:
Weigh PEG4000 200g, PEG6000 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, differential silica gel, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 400g, microcrystalline Cellulose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 96.12 ± 1.38%.(n＝6)
Embodiment 15:
Weigh PEG4000 200g, PEG6000 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 400g, lactose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 91.14 ± 2.11%.(n＝6)
Embodiment 16:
Weigh PEG4000 200g, PEG6000 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, differential silica gel, magnesium stearate were pulverized respectively to 100 mesh sieves, take 8g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 400g, microcrystalline Cellulose 100g, pre-paying starch 80g, carboxymethyl starch sodium 15g, sodium lauryl sulphate 6g mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 20 mesh sieves are granulated, 60 ℃ of wet grains are dry, 24 mesh sieve granulate: add 5g silicon dioxide, 1.5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 94.58 ± 1.58%.(n＝6)
Embodiment 17:
Weigh PEG2000 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 80 mesh sieves; Lactose, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 80 mesh sieves, take 5g polyvidone and be dissolved in appropriate 30% ethanol; Take respectively irbesartan solid dispersion 200g, lactose 60g, crospolyvinylpyrrolidone 10g, polyoxyethylene sorbitan monoleate 5g mix homogeneously, by the soft ability of 2% polyvidone+30% ethanol system, 18 mesh sieves are granulated, and 50 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 3g micropowder silica gel, 1g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 84.25 ± 2.13%.(n＝6)
Embodiment 18:
Weigh PEG10000 1800g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 120 mesh sieves; Microcrystalline Cellulose, carboxymethyl starch sodium, sodium lauryl sulphate, differential silica gel, magnesium stearate were pulverized respectively to 120 mesh sieves, take 10g hypromellose and be dissolved in appropriate 60% ethanol; Take respectively irbesartan solid dispersion 650g, microcrystalline Cellulose 180g, carboxymethyl starch sodium 20g, sodium lauryl sulphate 10g mix homogeneously, by the soft ability of 2%HPMC+60% ethanol system, 32 mesh sieves are granulated, and 80 ℃ of wet grains are dry, 40 mesh sieve granulate; Add 8g silicon dioxide, 6g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 89.48 ± 1.72%.(n＝6)
Embodiment 19:
Weigh sodium stearate 600g, glyceryl monostearate 300g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 90 mesh sieves; Lactose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 90 mesh sieves, take 5g polyvidone and be dissolved in appropriate 50% ethanol; Take respectively irbesartan solid dispersion 300g, lactose 60g, pre-paying starch 40g, crospolyvinylpyrrolidone 12g, polyoxyethylene sorbitan monoleate 6g mix homogeneously, by the soft ability of 2% polyvidone+50% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 4g micropowder silica gel, 2g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 83.67 ± 1.69%.(n＝6)
Embodiment 20:
Weigh Lac 600g, polyoxyethylene monostearate 600g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in hot-melt extruded granulator to granulate, and obtains irbesartan solid dispersion, is shattered 110 mesh sieves; Microcrystalline Cellulose, pre-paying starch, carboxymethyl starch sodium, sodium lauryl sulphate, differential silica gel, magnesium stearate were pulverized respectively to 110 mesh sieves, take 8g hypromellose and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 500g, microcrystalline Cellulose 40g, pre-paying starch 80g, carboxymethyl starch sodium 18g, sodium lauryl sulphate 7g, mix homogeneously, by the soft ability of 2%HPMC+40% ethanol system, 30 mesh sieves are granulated, 60 ℃ of wet grains are dry, 30 mesh sieve granulate; Add 6g silicon dioxide, 3g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 84.60 ± 1.52%.(n＝6)
Embodiment 21:
Weigh glycerin gelatine 1500g mix homogeneously, add irbesartan raw material 300g, mix homogeneously, adds hot melt in aerosol type solid dispersion draft machine to granulate, and obtains irbesartan solid dispersion, is shattered 100 mesh sieves; Lactose, carboxymethyl starch sodium, sodium lauryl sulphate, silicon dioxide, magnesium stearate were pulverized respectively to 100 mesh sieves, take 10g polyvidone and be dissolved in appropriate 40% ethanol; Take respectively irbesartan solid dispersion 600g, lactose 180g, crospolyvinylpyrrolidone 20g, polyoxyethylene sorbitan monoleate 8g mix homogeneously, by the soft ability of 2% polyvidone+40% ethanol system, 20 mesh sieves are granulated, and 60 ℃ of wet grains are dry, 24 mesh sieve granulate; Add 7g micropowder silica gel, 5g magnesium stearate, mix homogeneously, tabletting.This batch of external accumulative total of Irbesartan Tablets 45min stripping percentage rate is 81.06 ± 2.25%.(n＝6)
Claims (10)
1. the pharmaceutical composition of an irbesartan, it comprises irbesartan solid dispersion 200-650 weight portion, diluent 60-180 weight portion, disintegrating agent 10-20 weight portion, surfactant 5-10 weight portion, binding agent 5-10 weight portion, fluidizer 3-8 weight portion, lubricant 1-6 weight portion, described irbesartan solid dispersion comprises irbesartan and carrier material, described carrier material is selected from Polyethylene Glycol, poloxamer, stearic acid, sodium stearate, glyceryl monostearate, Lac, in polyoxyethylene monostearate or glycerin gelatine one or more, the weight ratio of described irbesartan and carrier material is l:1～6.
2. the pharmaceutical composition of irbesartan according to claim 1, it comprises irbesartan solid dispersion 400-450 weight portion, diluent 150-180 weight portion, disintegrating agent 15 weight portions, surfactant 6 weight portions, binding agent 6-8 weight portion, fluidizer 4-5 weight portion, lubricant 1.5 weight portions, described irbesartan solid dispersion forms by irbesartan with carrier material, described carrier material is selected from Polyethylene Glycol, poloxamer, stearic acid, sodium stearate, glyceryl monostearate, Lac, in polyoxyethylene monostearate or glycerin gelatine one or more, the weight ratio of described irbesartan and carrier material is l:1～2.
3. the pharmaceutical composition of irbesartan according to claim 1 and 2, wherein said Polyethylene Glycol is selected from PEG2000, PEG4000, PEG6000, in PEG8000 or 10000 one or more, described diluent is selected from lactose, in microcrystalline Cellulose or pre-paying starch one or more, described disintegrating agent is selected from carboxymethyl starch sodium or crospolyvinylpyrrolidone one or both, described surfactant is selected from sodium lauryl sulphate or polyoxyethylene sorbitan monoleate one or both, described binding agent is selected from polyvidone or hypromellose one or both, described fluidizer is selected from micropowder silica gel or silicon dioxide one or both, and described lubricant is magnesium stearate.
4. according to the pharmaceutical composition of the irbesartan described in claim 1-3 any one, wherein said irbesartan solid dispersion is to be prepared by hot-melt extruded granulator or aerosol type solid dispersion draft machine.
5. according to the pharmaceutical composition of the irbesartan described in claim 1-4 any one, wherein said pharmaceutical composition is tablet form.
6. prepare according to a method for the pharmaceutical composition of the irbesartan described in claim 1-4 any one, the method comprises the following steps:
1) irbesartan is mixed homogeneously with carrier material;
2) by hot-melt extruded granulator or aerosol type solid dispersion draft machine, said mixture is made to irbesartan solid dispersion;
3) irbesartan solid dispersion, diluent, disintegrating agent, surfactant, binding agent, fluidizer, lubricant were pulverized to 80-120 mesh sieve, then binding agent was dissolved in 30-60% alcoholic solution;
4) by step 3) irbesartan solid dispersion, diluent, disintegrating agent, the surfactant mix homogeneously of gained, add binder solution to granulate with 18-32 mesh sieve, 50-80 ℃ of oven dry, 24-40 mesh sieve granulate, then add fluidizer, mix lubricant even, obtain the pharmaceutical composition of described irbesartan.
7. the method for preparing the pharmaceutical composition of irbesartan according to claim 6, wherein the method is in step 4) further comprise afterwards tabletting step.
8. the method for preparing the pharmaceutical composition of irbesartan according to claim 6, step 3 wherein) irbesartan solid dispersion, diluent, disintegrating agent, surfactant, binding agent, fluidizer, lubricant were pulverized to 100 mesh sieves, then binding agent was dissolved in 40% alcoholic solution.
9. the method for preparing the pharmaceutical composition of irbesartan according to claim 6, step 4 wherein) by step 3) irbesartan solid dispersion, diluent, disintegrating agent, the surfactant mix homogeneously of gained, add binder solution to granulate with 20 mesh sieves, 60 ℃ of oven dry, 20-24 mesh sieve granulate, then add fluidizer, mix lubricant even, obtain the pharmaceutical composition of described irbesartan.
10. the pharmaceutical composition of irbesartan according to claim 1 is treated the purposes in hypertensive medicine in preparation.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107213124A (en) * | 2017-05-04 | 2017-09-29 | 广西大海阳光药业有限公司 | A kind of preparation of suppression therapy motion sickness and preparation method thereof |
| CN107233323A (en) * | 2017-05-04 | 2017-10-10 | 广西大海阳光药业有限公司 | A kind of medicine for treating chronic gastritis, hyperhydrochloria and preparation method thereof |
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Inventor after: Wang Yanjiao Inventor after: Yan Liying Inventor after: Wang Haisheng Inventor after: He Yan Inventor before: Wang Yanjiao Inventor before: Yan Liying Inventor before: Wang Haisheng Inventor before: He Yan |
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