CN110575441A

CN110575441A - Preparation method of valsartan tablets

Info

Publication number: CN110575441A
Application number: CN201910942054.2A
Authority: CN
Inventors: 苗得足; 黄京山; 陈传永; 高希恒; 杜玉泽
Original assignee: Reyoung Pharmaceutical Co Ltd
Current assignee: Reyoung Pharmaceutical Co Ltd
Priority date: 2019-09-30
Filing date: 2019-09-30
Publication date: 2019-12-17

Abstract

The invention relates to a preparation method of valsartan tablets, belonging to the technical field of pharmaceutical preparations. The preparation method of the valsartan tablet specifically comprises the following steps: (1) dissolving a surfactant in an ethanol solution with the mass concentration of 8-10% to obtain an adhesive; (2) premixing a filling agent, valsartan and a disintegrating agent, and adding the mixture into the adhesive in the step (1) for granulation; (3) pumping the wet granules obtained in the step (2) into a boiling granulation dryer for drying by using vacuum; (4) finishing the dried particles by using a crushing and granulating machine, and sucking the particles into a mixer by using vacuum; (5) and mixing the granules with an additional auxiliary material filler and a disintegrating agent, adding a flow aid and a lubricant, finally mixing, and tabletting after total mixing to obtain the valsartan tablets. The invention is simple and easy to operate, and the prepared medicine has high dissolution efficiency and stable quality and meets the GMP requirement.

Description

preparation method of valsartan tablets

Technical Field

The invention relates to a preparation method of valsartan tablets, belonging to the technical field of pharmaceutical preparations.

Background

With the continuous improvement of living standard, cardiovascular and cerebrovascular diseases and hypertension become main diseases which puzzle human beings. In the united states, valsartan is a drug used to treat hypertension, congestive heart failure, post-myocardial infarction. Swiss company obtains related patent rights in the United states and Europe respectively in 1995 and 1996, and the product is widely commented once being on the market, and particularly has the advantages of lasting and stable blood pressure reducing effect, small toxic and side effects and the like, so that the product is durable. For this reason many enterprises have made research and development.

CN 105769788A discloses a valsartan tablet and a preparation method thereof, which realize the prescription and process of directly tabletting valsartan whole powder.

CN 107684549A discloses a valsartan tablet and a preparation method thereof, which solve the problems of unreasonable component matching, complex preparation process, long production period and unstable product quality of a valsartan preparation in the prior art.

CN 108553435A discloses a valsartan tablet and a preparation method thereof, which achieve the integrity and stability of particles, improve the qualification rate of the valsartan tablet, uniformly mix ingredients of the valsartan tablet, ensure that the pharmacological ingredients are uniformly distributed in the valsartan tablet, and reduce the large side effect caused by the overproof valsartan content in the valsartan tablet.

However, the valsartan tablet produced by the prior art still has the problem of low dissolution efficiency of the product, and the improvement is urgently needed.

Disclosure of Invention

The invention aims to solve the problems that: overcomes the defects of the prior art, provides a preparation method of valsartan tablets, is simple and feasible, and the prepared medicament has high dissolution efficiency and stable quality and meets the GMP requirement.

The preparation method of the valsartan tablet specifically comprises the following steps:

(1) Dissolving a surfactant in an ethanol solution with the mass concentration of 8-10% to obtain an adhesive;

(2) Premixing a filling agent, valsartan and a disintegrating agent, and adding the mixture into the adhesive in the step (1) for granulation;

(3) Pumping the wet granules obtained in the step (2) into a boiling granulation dryer for drying by using vacuum;

(4) Finishing the dried particles by using a crushing and granulating machine, and sucking the particles into a mixer by using vacuum;

(5) and mixing the granules with an additional auxiliary material filler and a disintegrating agent, adding a flow aid and a lubricant, finally mixing, and tabletting after total mixing to obtain the valsartan tablets.

The filler is one or more of microcrystalline cellulose, lactose, mannitol or carboxymethyl starch sodium.

The disintegrant is one or more of microcrystalline cellulose, carboxymethyl starch sodium (disintegrating agent) or polyvidone K30.

Preferably, the surfactant is sodium lauryl sulfate.

Preferably, the glidant is silicon dioxide.

Preferably, the lubricant is magnesium stearate.

in the step (3), drying is carried out until the water content is less than or equal to 6.0 percent by mass. Preferably, the drying is carried out until the moisture mass content is less than or equal to 4.0 percent.

The filler in the step (2) and the filler in the step (5) have the same components, and the mixing ratio is 1:0.5-1, in the step, the filler is added in two parts, one part is used as an internal filler, the other part is used as an external filler, and the effective components and other auxiliary materials of the medicine can be better mixed through internal and external matching, so that the mixing effect and the uniformity of the composite sheet are improved.

In the step (2), the components of the disintegrating agent in the step (5) are the same, the mixing ratio is 1:0.5-1, in the step, the disintegrating agent is added in two parts, one part is used as an internal disintegrating agent, the other part is used as an external disintegrating agent, and through internal and external matching, the disintegration time is shortened, and the dissolution speed of the medicine is improved.

According to the invention, the surfactant is dissolved in the ethanol to be used as a binder, namely the ethanol is modified by the surfactant, the preferable conventional function of the sodium dodecyl sulfate is used as an emulsifier of the medicament, and the sodium dodecyl sulfate is used as the surfactant in the application, so that the solubility of the valsartan serving as an insoluble medicament can be increased, and the dissolution rate of the valsartan is further improved.

The invention has the following beneficial effects:

(1) The active ingredients of the valsartan tablets produced by the method can be quickly dissolved out, so that the blood pressure can be quickly reduced, the valsartan tablets have a good curative effect on primary hypertension, and the use value of the valsartan tablets is better improved;

(2) The invention has stable process, the production process meets GMP requirements, and the prepared product has stable quality and is suitable for industrial mass production.

Detailed Description

The present invention is further illustrated by the following examples, which are not intended to limit the practice of the invention.

Comparative example 1

1. Prescription

2. Process for the preparation of a coating

Weighing mannitol, microcrystalline cellulose, sodium dodecyl sulfate and valsartan according to the prescription amount, mixing, adding purified water for granulation, detecting the drying weight loss after mixing is finished, and controlling the water content to be not more than 4.0%. Adding additional auxiliary materials of microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate and silicon dioxide, uniformly mixing, and tabletting to obtain the valsartan tablets.

Comparative example 2

1. Prescription

2. Process for the preparation of a coating

Comparative example 3

1. prescription

2. Process for the preparation of a coating

Weighing mannitol, carboxymethyl starch sodium, sodium dodecyl sulfate and valsartan according to the formula amount, mixing, adding ethanol for granulation, detecting the drying weight loss after mixing is finished, and controlling the water content to be not more than 4.0%. Adding additional auxiliary materials of microcrystalline cellulose, sodium carboxymethyl starch (quick disintegrating king), magnesium stearate and silicon dioxide, uniformly mixing, and tabletting to obtain the valsartan tablets.

Example 1

1. Prescription

2. Process for the preparation of a coating

Weighing mannitol, carboxymethyl starch sodium (quick-disintegrating king) and valsartan according to the prescription amount, mixing, adding an ethanol solution (with the mass concentration of 8%) dissolved with sodium dodecyl sulfate for granulation, detecting the drying weight loss after mixing is finished, and controlling the water content to be not more than 4.0%. Adding additional auxiliary materials of microcrystalline cellulose, sodium carboxymethyl starch (quick disintegrating king), magnesium stearate and silicon dioxide, uniformly mixing, and tabletting to obtain the valsartan tablets.

The dissolution performance of the products prepared in the comparison examples 1-3 and example 1 was examined by the method under the dissolution item of the second valsartan tablet in the chinese pharmacopoeia of 2015 edition, and the results are shown in table 1.

TABLE 1 dissolution of Valsartan tablets

The valsartan content of the products prepared in comparative examples 1-3 and example 1 was examined and the results are shown in table 2.

table 2 provides the labeled amount of valsartan tablets for explaining whether the content in the comparative examples and examples is acceptable or not, which is a precondition for evaluating the dissolution performance.

TABLE 2 labeled amounts of valsartan tablets

note: in the pharmaceutical industry, the difference of tablet weight and detection error can cause the content to fluctuate above and below 100%.

the data show that in the comparative example 1, the valsartan is unqualified in dissolution rate and poor in dissolution effect, and the content is qualified after the sampling time is prolonged.

in comparative example 2, after the binder was adjusted, the particle size was improved to some extent, and the dissolution was improved as seen by examining the dissolution rate of valsartan, but the effect was still poor.

In comparative example 3, after the wet granulation material was adjusted, the dissolution result was further improved, and the detection result was not uniform, which may be caused by non-uniform adjustment of the carboxymethyl starch sodium in the wet granulation material.

In the embodiment 1, sodium dodecyl sulfate is changed to be dissolved in ethanol and then added as an adhesive, and common carboxymethyl starch sodium is changed to be carboxymethyl starch sodium (disintegrating rapidly), so that the dissolution effect is obviously improved, and the detection result is qualified and meets the quality standard requirement.

the process of the embodiment 1 is further improved compared with the processes of the comparative examples 1, 2 and 3, in order to ensure the qualified dissolution rate, sodium dodecyl sulfate is dissolved in ethanol to be used as a bonding agent for granulation, the sodium carboxymethyl starch is adjusted, and the sodium carboxymethyl starch (Suqian) with higher dissolution rate is modified, and the sodium carboxymethyl starch meets the quality standard requirement through the inspection of a quality inspection department, the production process is controllable, the reproducibility between batches is good, the GMP standard requirement is met, and the guarantee is provided for ensuring the qualified dissolution rate of the valsartan tablets.

Claims

1. A preparation method of valsartan tablets is characterized by comprising the following steps:

2. The process for preparing valsartan tablets according to claim 1, characterized in that: the filler is one or more of microcrystalline cellulose, lactose, mannitol or carboxymethyl starch sodium.

3. The process for preparing valsartan tablets according to claim 1, characterized in that: the disintegrant is one or more of microcrystalline cellulose, carboxymethyl starch sodium or polyvidone K30.

4. The process for preparing valsartan tablets according to claim 1, characterized in that: in the step (3), drying is carried out until the water content is less than or equal to 6.0 percent by mass.

5. The process for preparing valsartan tablets according to claim 4, wherein: in the step (3), drying is carried out until the water content is less than or equal to 4.0 percent by mass.

6. The process for preparing valsartan tablets according to claim 1, characterized in that: the filler components in the step (2) and the step (5) are the same, and the mixing ratio is 1: 0.5-1.

7. The process for preparing valsartan tablets according to claim 1, characterized in that: the components of the disintegrating agent in the step (2) and the component of the disintegrating agent in the step (5) are the same, and the mixing ratio is 1: 0.5-1.

8. The process for preparing valsartan tablets according to claim 1, characterized in that: the surfactant is sodium dodecyl sulfate.