CN103191076B - A kind of preparation method of irbesartan tablet - Google Patents

Abstract

The invention discloses a kind of irbesartan tablet and preparation method thereof, said preparation is formed by tabletting after medicine-containing particle and pharmaceutically acceptable auxiliary materials and mixing, described medicine-containing particle is prepared as follows forming: be dissolved in sodium hydrate aqueous solution by irbesartan, is dried to obtain medicine-containing particle after adding polyvinylpolypyrrolidone absorption.Invention formulation dissolution rate is fast, and without micropowder silica gel, decreases potential safety hazard.

Description

A kind of preparation method of irbesartan tablet

Technical field

The invention belongs to pharmaceutical technology field, be specifically related to a kind of irbesartan tablet and preparation method thereof.

Background technology

Hypertension is the cardiovascular disease that sickness rate raises year by year, as blood pressure can not be advantageously controlled for a long time, it will The vitals such as the heart, brain, kidney are produced serious consequence, even threat to life.At present depressor kind is a lot, as calcium from Sub-antagonist, beta-blocker, converting enzyme inhibitor (ACEI), diuretic, alpha-blocking agent etc., but still Having many hypertensive patients to fail to obtain good treatment, this is relevant with many factors, wherein pair drug-induced with majority It is closely related that effect causes drug withdrawal to have.Irbesartan is a kind of new Ang II receptor blocking agent, makees in hypertension therapeutic With significantly, effect is equal to or is slightly better than ATE I receptor blocking agent and losartan, and side effect is little, better tolerance, and curative effect is steady Fixed, it is suitable for Mild or moderate hypertension patient, can be as a line depressor at Clinical practice.

Owing to the Electrostatic Absorption of irbesartan is relatively strong, raw material and adjuvant combine insecure, and the granule that wet granulation is made is often Mobility is very poor, and in tableting processes, easily produces bonding die phenomenon, and therefore currently available technology mostly makes in prescription With micropowder silica gel, on the one hand this material can weaken Electrostatic Absorption, alleviates bonding die problem, on the other hand can strengthen material stream Dynamic property.But, micropowder silica gel is more fluffy, and has conglomeration, therefore needs in actual production process and other adjuvants Mix use of sieving.In screening process, usually can produce the substantial amounts of particulate matter disseminated in atmosphere.These are at air In the particulate matter that disseminates the respiratory tract of Workshop Production personnel can be produced and stimulate, be directly detrimental to health, be therefore a kind of Potential potential safety hazard.Carry out it addition, the sifting step of micropowder silica gel is frequently in total mixed operation, typically can use screen cloth Sieve by hand, which increases the probability that material pollutes, thus cause the quality of medicine can not be guaranteed.

Irbesartan belongs to the Biopharmaceutics Classification system two class medicine of slightly solubility, and the dissolubility in water is low, oral raw Thing availability is poor.Research shows, for Biopharmaceutics Classification system two class medicine, process in leaching is its biology of restriction The key factor of availability.According to Ostwald Freundrich equation, drug-eluting speed and size of pharmaceutical particles in Inverse ratio, reduces drug particles particle diameter and its dissolution rate can be greatly improved, thus significantly improve the bioavailability of medicine, Reduce individual variation, reduce toxic and side effects.If but used routine techniques to reduce diameter of aspirin particle, then would be equivalent to increase further Having added surface area, preparation produces and is more difficult to.It is a kind of lint shape material that EP0747050B1 discloses irbesartan, There is relatively low bulk density, this character make it difficult to make high amount of drug have that weight is consistent, hardness and preferable sheet The tabloid of agent character.It addition, irbesartan has electrostatic, the surface of tablet machine drift head and mould can be adhered to, draw Play tabletting difficulty.The low soluble of irbesartan there is also a kind of challenge, the small size of slice, thin piece to be kept, and only can add a small amount of Excipient to promote moistening, disintegrate and final the most quickly and completely drug release.

US5994348 discloses a kind of irbesartan pharmaceutical composition, comprises active constituents of medicine irbesartan in its prescription And hydrochlorothiazide, select lactose, microcrystalline Cellulose be diluent, pregelatinized Starch or polyvidone k30 be binding agent, friendship Connection carmethose be disintegrating agent, antiplastering aid micropowder silica gel, magnesium stearate lubricant and optional surfactant and/ Or coloring agent.US200903005 disclose a kind of containing irbesartan and lactose but there is no the medicine system of surfactant Agent, this prescription does not contains surfactant and lactose and principal agent ratio 1: between 4-4: 1, used by this prescription, lactose yield is too Greatly, and the mobility of lactose own is bad, and the mobility of granule is very poor, easy bonding die during tabletting, causes production difficulty.

CN102309456A discloses a kind of Irbesartan sodium micro composite powder and tablet and preparation method thereof, said preparation bag Including amorphous and crystal type Irbesartan sodium micro composite powder and tablet and preparation method thereof, drug particles mean diameter is 200-900nm, amorphous receives micro-composite granule 10min leachable more than 90%, and the amorphous micro-tablet 5min that receives is solvable Go out more than 90%, but technique is complex.CN101912390A discloses a kind of irbesartan Pharmaceutical composition, its bag Containing accounting for weight of formulation percentage ratio 30-70% irbesartan or its pharmacy can use salt, wherein the particle diameter employing laser of irbesartan D (V, 0.9)≤200 μm that granularity method is measured, compositions is substantially without micropowder silica gel.But, medicine powder particle diameter is more Little, electrostatic interaction is the strongest, and powder flowbility is the poorest, and practical operation difficulty is big.

Summary of the invention

In view of the deficiencies in the prior art, it is an object of the invention to grind by the prescription of preparation and technique are carried out lot of experiments Study carefully, be finally obtained a kind of without micropowder silica gel, irbesartan tablet that dissolution is fast and preparation method thereof.

The object of the present invention is achieved like this:

A kind of irbesartan tablet, auxiliary with pharmaceutically acceptable as the medicine-containing particle of sole active agent by irbesartan After material mixing, tabletting forms, and described medicine-containing particle is prepared as follows forming: by irbesartan and be dissolved in hydroxide In sodium water solution, add polyvinylpolypyrrolidone absorption, be dried to obtain medicine-containing particle.

Preferably, above-mentioned irbesartan tablet, wherein irbesartan is 1:1.5-3 with the weight ratio of polyvinylpolypyrrolidone.

Preferably, above-mentioned irbesartan tablet, the molar concentration of wherein said sodium hydrate aqueous solution is 0.01-0.5mol/L。

It is further preferred that above-mentioned irbesartan tablet, the molar concentration of wherein said sodium hydrate aqueous solution is 0.05-0.2mol/L。

Irbesartan tablet of the present invention, the most pharmaceutically acceptable adjuvant includes filler and lubricant.Described One or more in microcrystalline Cellulose, lactose, mannitol, starch and pregelatinized Starch of filler.Preferably institute The filler stated is microcrystalline Cellulose.Described lubricant is the one in magnesium stearate, Pulvis Talci and sodium stearyl fumarate Or it is multiple.Preferably described lubricant is magnesium stearate.

Second object of the present invention be to provide the preparation method of a kind of above-mentioned irbesartan tablet, the method include as Lower step: be dissolved in sodium hydrate aqueous solution by irbesartan, adds polyvinylpolypyrrolidone absorption, is then dried Medicine-containing particle；Medicine-containing particle is mixed homogeneously with pharmaceutically acceptable adjuvant, tabletting.

The preparation method of above-mentioned irbesartan tablet, wherein said pharmaceutically acceptable adjuvant includes filler and profit Lubrication prescription；Described filler one or many in microcrystalline Cellulose, lactose, mannitol, starch and pregelatinized Starch Kind；Described lubricant is one or more in magnesium stearate, Pulvis Talci and sodium stearyl fumarate.

Compared with prior art, invention formulation does not contains micropowder silica gel, decreases potential safety hazard.It addition, the present inventor's wound The property made irbesartan is dissolved in sodium hydroxide solution, is dried, then with medicine after adding polyvinylpolypyrrolidone absorption Acceptable adjuvant mix homogeneously tabletting on.Owing to medicine dissolution is in sodium hydroxide solution, then use polyvinylpolypyrrolidone Absorption, therefore medicine is dispersed on polyvinylpolypyrrolidone with molecularity, obtains unforeseeable effect in terms of dissolution rate.

Specific embodiment

Following example further describe preparation process and the beneficial effect of the present invention, and embodiment is only used for the purpose of illustration, Not limiting the scope of the invention, those of ordinary skill in the art are obviously changed according to what the present invention made and repair simultaneously Within decorations are also contained in the scope of the invention.

Embodiment 1

Preparation technology:

Irbesartan is dissolved in sodium hydrate aqueous solution, add polyvinylpolypyrrolidone, be dried, by dried powder with Cross the microcrystalline Cellulose of 100 mesh sieves, lactose, Pulvis Talci mix homogeneously, tabletting, to obtain final product.

Embodiment 2

Preparation technology:

Irbesartan is dissolved in sodium hydrate aqueous solution, add polyvinylpolypyrrolidone, be dried, by dried powder with Cross the microcrystalline Cellulose of 100 mesh sieves, magnesium stearate mix homogeneously, tabletting, to obtain final product.

Embodiment 3

Preparation technology:

Irbesartan is dissolved in sodium hydrate aqueous solution, adds polyvinylpolypyrrolidone, is dried, by dried powder and mistake The microcrystalline Cellulose of 100 mesh sieves, magnesium stearate mix homogeneously, tabletting, to obtain final product.

Comparative example 1

Preparation technology:

Irbesartan is dissolved in sodium hydrate aqueous solution, adds carboxymethyl starch sodium, be dried, by dried mixing Thing is mixed homogeneously with the microcrystalline Cellulose of 100 mesh sieves, magnesium stearate excessively, and tabletting to obtain final product.

Comparative example 2

Preparation technology:

By irbesartan comminution by gas stream, make D90 < 10 μm, with cross the microcrystalline Cellulose of 100 mesh sieves, polyvinylpolypyrrolidone, Magnesium stearate mix homogeneously, tabletting, to obtain final product.

Embodiment 4 dissolution determination is tested

The tablet sampling preparing embodiment 1-3 and comparative example 1-2 measures dissolution, medium 0.1M hydrochloric acid 1000ml, paddle method 50rpm, sample at 5min, 30min respectively, detection.

Table 1 embodiment dissolution determination result

Embodiment	5min dissolution (%)	30min dissolution (%)
			Embodiment 1	98.6	99.5
Embodiment 2	98.8	99.8
			Embodiment 3	99.8	99.7
Comparative example 1	52.1	87.6
			Comparative example 2	50.4	86.5

From the result of the test of table 1 it can be seen that the slice, thin piece dissolution prepared of embodiment of the present invention 1-3 is rapid, 5min is basic Dissolution completely；The disintegrating agent of comparative example 1 uses carboxymethyl starch sodium to adsorb, the slice, thin piece dissolution prepared by result Slowly；Comparative example 2 uses comminution by gas stream to process raw material, but the medicine after processing can be assembled, and causes dissolution the slowest.

Claims (9)

1. an irbesartan tablet, formed by tabletting after irbesartan medicine-containing particle and pharmaceutically acceptable auxiliary materials and mixing as sole active agent, it is characterized in that: described medicine-containing particle is prepared as follows forming: irbesartan is dissolved in sodium hydrate aqueous solution, add polyvinylpolypyrrolidone absorption, be dried to obtain medicine-containing particle；Irbesartan is 1:1.5-3 with the weight ratio of polyvinylpolypyrrolidone.

Irbesartan tablet the most according to claim 1, it is characterised in that: the molar concentration of described sodium hydrate aqueous solution is 0.01-0.5mol/L.

Irbesartan tablet the most according to claim 2, it is characterised in that: the molar concentration of described sodium hydrate aqueous solution is 0.05-0.2mol/L.

4. according to the irbesartan tablet described in any one of claim 1-3, it is characterised in that: described pharmaceutically acceptable adjuvant includes filler and lubricant.

Irbesartan tablet the most according to claim 4, it is characterised in that: one or more in microcrystalline Cellulose, lactose, mannitol, starch and pregelatinized Starch of described filler.

Irbesartan tablet the most according to claim 4, it is characterised in that: described filler is microcrystalline Cellulose.

Irbesartan tablet the most according to claim 4, it is characterised in that: described lubricant is one or more in magnesium stearate, Pulvis Talci and sodium stearyl fumarate.

8. the preparation method according to the irbesartan tablet described in any one of claim 1-3, it is characterised in that comprise the steps: to be dissolved in sodium hydrate aqueous solution irbesartan, adds polyvinylpolypyrrolidone absorption, is then dried to obtain medicine-containing particle；Medicine-containing particle is mixed homogeneously with pharmaceutically acceptable adjuvant, tabletting.

The preparation method of irbesartan tablet the most according to claim 8, it is characterised in that: described pharmaceutically acceptable adjuvant includes filler and lubricant；One or more in microcrystalline Cellulose, lactose, mannitol, starch and pregelatinized Starch of described filler；Described lubricant is one or more in magnesium stearate, Pulvis Talci and sodium stearyl fumarate.