CN102475707B - Preparation method for compound losartan potassium-hydrochlorothiazide pharmaceutical composition - Google Patents

Abstract

The invention relates to a preparation method for a losartan potassium-hydrochlorothiazide tablet. The losartan potassium-hydrochlorothiazide tablet is characterized in that: after losartan potassium and starch are mixed, 10% of starch slurry is used to prepare particles with a suitable hardness; hydrochlorothiazide, cross linked sodium carboxymethyl cellulose and lactose are mixed, and particles with a proper hardness are prepared from an obtained mixture by using 5% of a polyvinylpyrrolidone K30 solution; the two kinds of particles and magnesium stearate are uniformly mixed and then are subjected to tabletting. According to the invention, a low dissolution rate caused by interaction among drugs in primary granulation is avoided, and an in vitro dissolution rate can be improved greatly, thereby enhancing bioavailability.

Description

The preparation method of compound recipe losartan potassium hydrochlorothiazide pharmaceutical composition

Technical field

The preparation method that the present invention relates to losastan potassium/hydrochlorothiazide tablets a kind of.

Background technology

Hypertension is the modal cardiovascular disease in countries in the world, and its prevalence, up to 10%-20%, can cause the heart, cerebrovascular and nephropathy, is one of principal disease of harm humans health.More than the 1O of 1979 ~ 1991 between year, China's Prevalence of Hypertension increases 25%.According to World Health Organization's prediction, the year two thousand twenty, noninfectious disease will occupy 79% of China's cause of death, and its cardiovascular disease will occupy first place.Report is had to point out, Treatment of Hypertension affirmative minimizing cardiovascular is lethal, disability rate, remarkable result is had to preventing the progress of apoplexy, coronary heart disease, heart failure, kidney disease, developing into more serious hypertension and reducing general mortality rate, particularly evident to reduction Incidence of CHD.

At present, clinical conventional antihypertensive comprises: diuretic; Tonin depressant and angiotensin-ii-receptor (AT ₁) blocking agent; Beta-blocker; Cerebrocrast; Sympathetic nerve depressant and expansion blood vessel medicine this six large classes, wherein diuretic (as hydrochlorothiazide), tonin depressant (as captopril) and angiotensin-ii-receptor (AT ₁) blocking agent (as Losartan Potassium); Cerebrocrast (as Amlodipine Besylate Tablet) is an at present line medication clinically, through clinical verification determined curative effect for many years, few side effects, and as angiotensin-ii-receptor (AT ₁) the representative Losartan Potassium outstanding person wherein especially of blocking agent, Losartan Potassium is mainly through blocking angiotensinⅡ and AT ₁receptors bind, makes relaxing the VSM and plays hypotensive effect.Simultaneously the also effect such as vascular smooth muscle hypertrophy, endothelial dysfunction, water-sodium retention that causes of inhibition angiotensin II, has the heart, kidney, vascular protection effect.Its main advantage is that blood pressure lowering is steady, untoward reaction is few, especially the cough that angiotensin converting enzyme inhibitor (ACEI) more often causes is not had, thus add its compliance, and can also urate excretion be promoted, reduce serum uric acid level, be better than tonin depressant through domestic and international clinical trial for many years and its curative effect of application, cerebrocrast, and side effect also will be less than said two devices.Hydrochlorothiazide is middle effect diuretic, logical

Cross suppression Distal convoluted tubule near-end K ⁺-Na ⁺-2Cl co-transport carrier, suppress NaCl to absorb again, thus reach the object of diuretic antihypertensive, the applicating history of hydrochlorothiazide is remote, and clinical practice safely, effectively, reliably, its main side effect is that serum uric acid level increases.

Currently available technology shows, and Losartan Potassium and amlodipine interact, and affect the stripping rate of release of its amlodipine, conventional method increases adjuvant volume ratio exactly, increase sheet weight, but effect is not still fairly obvious.

Summary of the invention

The present invention has prepared losastan potassium/hydrochlorothiazide tablets, adopts wet granulation technology to prepare two kinds of granules, obviously overcomes in existing production technology and adopt a kind of granule to prepare, make drug drug interaction, affect drug release.Therefore, the present inventor has made great efforts to solve this problem relevant to conventional formulation, and successfully develops a kind of oral losartan potassium hydrochlorothiazide composition of improvement.There is higher stability and higher bioavailability.

The object of this invention is to provide a kind of oral losastan potassium/hydrochlorothiazide tablets, it has the performance characteristic of high expectations in bioavailability and high stability improving.

Another object of the present invention is to provide a kind of method utilizing described compositions to prepare losastan potassium/hydrochlorothiazide tablets.

A preparation method for losastan potassium/hydrochlorothiazide tablets, is characterized in that, each component composition and proportioning are:

Granule 1

Losartan Potassium 50g

Starch 150g

10% starch slurry is appropriate

Granule 2

Hydrochlorothiazide 12.5g

Cross-linking sodium carboxymethyl cellulose 10g

Lactose 150g

5% PVP K30 solution is appropriate

Magnesium stearate 2g

Make 1000,

Preparation process is as follows:

1) recipe quantity Losartan Potassium is sieved, after mixing homogeneously with starch, adopt 10% starch slurry to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, make moisture be less than 5%, for subsequent use;

2) recipe quantity hydrochlorothiazide is crushed to particle diameter qualified, for subsequent use;

3) by the hydrochlorothiazide of recipe quantity, cross-linking sodium carboxymethyl cellulose, lactose mix homogeneously, adopt 5% PVP K30 solution to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, moisture is made to be less than 5%, for subsequent use;

4) always mix: by 2) and 3) granule mixs homogeneously with magnesium stearate by prescription;

5) tabletting, to obtain final product.

Advantage of the present invention is technical maturity, simple to operate, is applicable to industrial large-scale production.

Losartan Potassium amlodipine of the present invention is a kind of resisting hypertension medicine.The present invention has following advantage:

1) stability of amlodipine can be improved: adopt granulating process respectively to avoid amlodipine and contact in aqueous environments with Losartan Potassium;

2) preparation method of Losartan Potassium amlodipine provided by the present invention, not only well overcome the problem affecting dissolution rate that Losartan Potassium causes amlodipine, and adopt Losartan Potassium amlodipine good fluidity prepared by the method, dissolution is good, content uniformity is not obvious.

Detailed description of the invention

Below in conjunction with embodiment, the present invention is described in further detail, but the non-scope being only limitted to these embodiments of scope of the present invention should be understood.

embodiment 1

Granule 1

Losartan Potassium 50g

Starch 150g

10% starch slurry is appropriate

Granule 2

Hydrochlorothiazide 12.5g

Cross-linking sodium carboxymethyl cellulose 10g

Lactose 150g

5% PVP K30 solution is appropriate

Magnesium stearate 2g

Make 1000

Preparation process is as follows:

1) recipe quantity Losartan Potassium is sieved, after mixing homogeneously with starch, adopt 10% starch slurry to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, make moisture be less than 5%, for subsequent use;

2) recipe quantity hydrochlorothiazide is crushed to particle diameter qualified, for subsequent use;

3) by the hydrochlorothiazide of recipe quantity, cross-linking sodium carboxymethyl cellulose, lactose mix homogeneously, adopt 5% PVP K30 solution to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, moisture is made to be less than 5%, for subsequent use;

4) always mix: by 2) and 3) granule mixs homogeneously with magnesium stearate by prescription;

5) tabletting, to obtain final product.

comparative example 2

Losartan Potassium 50g

Starch 150g

Hydrochlorothiazide 12.5g

Cross-linking sodium carboxymethyl cellulose 10g

Lactose 150g

5% PVP K30 solution is appropriate

Magnesium stearate 2g

Make 1000

Preparation process is as follows:

1) recipe quantity hydrochlorothiazide is crushed to particle diameter qualified, for subsequent use;

2) by the Losartan Potassium of recipe quantity, hydrochlorothiazide, starch, cross-linking sodium carboxymethyl cellulose, lactose mix homogeneously, adopt 5% PVP K30 solution to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, moisture is made to be less than 5%, for subsequent use;

3) always mixing: by 2) granule mixs homogeneously with magnesium stearate by prescription;

4) tabletting, to obtain final product.

test example 1

embodiment 1 is carried out long term test and accelerated test with comparative example 2, and result of the test sees the following form:

Constant temperature accelerated stability test result

Room temperature keeps sample stability test result

From above test data result, the embodiment 1 adopting the present invention to prepare can improve the dissolution rate of hydrochlorothiazide preferably, and then improves bioavailability further, and embodiment 1 is better than comparative example 2.And there is good stability.

Claims (1)

1. a preparation method for losastan potassium/hydrochlorothiazide tablets, is characterized in that, each component composition and proportioning are:

Granule 1

Losartan Potassium 50g

Starch 150g

10% starch slurry is appropriate

Granule 2

Hydrochlorothiazide 12.5g

Cross-linking sodium carboxymethyl cellulose 10g

Lactose 150g

5% PVP K30 solution is appropriate

Magnesium stearate 2g

Make 1000,

Preparation process is as follows:

1) recipe quantity Losartan Potassium is sieved, after mixing homogeneously with starch, adopt 10% starch slurry to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, make moisture be less than 5%, for subsequent use;

2) recipe quantity hydrochlorothiazide is crushed to particle diameter qualified, for subsequent use;

3) by the hydrochlorothiazide of recipe quantity, cross-linking sodium carboxymethyl cellulose, lactose mix homogeneously, adopt 5% PVP K30 solution to obtain the soft material of suitable stiff, adopt 20 eye mesh screens to granulate, dry under 60 DEG C of conditions, moisture is made to be less than 5%, for subsequent use;

4) always mix: by 2) and 3) granule mixs homogeneously with magnesium stearate by prescription;

5) tabletting, to obtain final product.