CN110051639B

CN110051639B - Rapidly disintegrating nicergoline tablet and preparation method thereof

Info

Publication number: CN110051639B
Application number: CN201910196333.9A
Authority: CN
Inventors: 周立明; 张晓轩; 白培锋; 武晶晶; 刘少华; 张莉; 张树生; 董进臣
Original assignee: Hebei Jiamai Pharmaceutical Technology Co ltd
Current assignee: Hubei Kelaiwei Biopharmaceutical Co ltd
Priority date: 2019-03-15
Filing date: 2019-03-15
Publication date: 2021-08-31
Anticipated expiration: 2039-03-15
Also published as: CN110051639A

Abstract

The invention relates to a preparation method of a rapidly disintegrating nicergoline tablet, which comprises the following essential key steps: namely, the microcrystalline cellulose-sodium carboxymethylcellulose granules are firstly prepared by adopting a wet granulation method and then mixed with other auxiliary materials, and the granules can rapidly disintegrate the prepared nicergoline tablets. The tabletting process provided by the invention is a powder direct pressing process: directly mixing the prepared microcrystalline cellulose-carboxymethylcellulose sodium granules, nicergoline, calcium hydrogen phosphate and magnesium stearate; then tabletting, coating and packaging by aluminum plastic to obtain the finished product. The nicergoline tablet prepared by the invention has qualified all inspection indexes, has the disintegration time limit less than or equal to 2 minutes, can be quickly and completely disintegrated in an inspected dissolution medium, and realizes quick dissolution. The formula provided by the invention does not use a disintegrant which is easy to absorb moisture, and the prepared nicergoline tablets have excellent stability. The preparation method of the nicergoline tablet provided by the invention is novel, has a simple process, and well solves the problems of no disintegration and poor stability of the nicergoline tablets on the market at present.

Description

Rapidly disintegrating nicergoline tablet and preparation method thereof

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, relates to a preparation method of a rapidly disintegrating tablet, and particularly relates to a preparation method of a rapidly disintegrating nicergoline tablet.

Background

As the population of society ages, memory and cognitive decline are physiological phenomena inevitable for normal aging, while dementia, mild cognitive impairment and normal aging are cognitive decline states of varying degrees that occur in the elderly, and neurological diseases have become a big killer threatening human health. Taking dementia as an example, senile dementia, also known as alzheimer disease, has become the fourth killer of the elderly people after cardiovascular diseases, malignant tumors and cerebral apoplexy. The disease is a primary degenerative encephalopathy, occurs in the old and the early stages of the old, and is multiplied with the aging, the prevalence rate is 4-8% after 60 years of age, 10% after 65 years of age and more than 30% after 80 years of age. The number of patients with senile dementia in China also shows a remarkable rising trend, and according to statistics, the total number of patients is about 600 ten thousand at present, which is the first in the world, and about 1/4 of patients in China in the world.

Nicergoline is a semisynthetic ergoline derivative. Has alpha-receptor blocking and blood vessel dilating effects. Can enhance energy metabolism of brain cells, and increase oxygen and glucose utilization. Promoting the conversion of neurotransmitter dopamine to increase the conduction of nerves, strengthening the synthesis of brain protein, effectively improving the memory and learning ability, recovering the normal function of the neuron and quickly improving the symptom of brain decline, thereby effectively improving the symptom of brain decline. The clinical nicergoline is widely applied with unique curative effect.

Nicergoline is sensitive to moisture and heat and is easily degraded under high temperature and humidity conditions. In the compatibility research of nicergoline and auxiliary materials, the nicergoline and different types of disintegrants are found to have poor compatibility under high humidity conditions, which is related to the fact that the disintegrants are easy to absorb moisture. Nicergoline is a BCS classification 2 type drug, belongs to a low-solubility high-permeability drug, and the dissolution of nicergoline in a preparation is a key factor influencing the bioavailability. The nicergoline tablets on the market at present have better stability, but have poor disintegration in an in vitro medium and low in vivo bioavailability; some are good in disintegration, but poor in stability, rapid in impurity growth and difficult to be qualified in the effective period. The technical problem to be overcome is to balance the mutual influence between stability and disintegration to obtain a preparation which meets the requirements of both.

Attempts were made to prepare nicergoline tablets using nicergoline, microcrystalline cellulose, calcium hydrogen phosphate, sodium carboxymethylcellulose and magnesium stearate. Wherein the coating is a film coating or a sugar coating. In the composition of the tablet core, the auxiliary materials which are beneficial to disintegration are microcrystalline cellulose and sodium carboxymethylcellulose, wherein the microcrystalline cellulose is a filler, has a weak disintegration effect and is more in market models; sodium carboxymethylcellulose is a hydrophilic adhesive and is classified into low-viscosity, medium-viscosity and high-viscosity types according to different viscosities in the market. With the above formulation, in order to achieve the purpose of rapid disintegration and dissolution, it is generally thought that microcrystalline cellulose of different types is used to improve the disintegration; or the sodium carboxymethylcellulose with different types is replaced to improve the hydrophilicity.

Through tests, various types of microcrystalline cellulose such as small-particle-size PH101, large-particle-size PH200, high-density PH301 and low-density KG802, which are commercially available in domestic markets at present, and sodium carboxymethyl cellulose such as low-viscosity 7LF PH, medium-viscosity 7MF PH and high-viscosity 7HF PH, which are different in viscosity, are respectively adopted, and the auxiliary material and the main material are mixed by adopting a conventional method, and then the nicergoline tablet is prepared by adopting a direct compression process, or the nicergoline tablet is prepared by adopting the processes such as wet granulation, drying, granule finishing, sieving, tabletting and the like, and cannot be completely disintegrated and is slowly dissolved out.

Disclosure of Invention

Based on the problems of the existing nicergoline tablets, the invention provides a preparation method of nicergoline tablets, which comprises the steps of firstly granulating microcrystalline cellulose and sodium carboxymethyl cellulose in a formula, mixing the prepared microcrystalline cellulose-sodium carboxymethyl cellulose granules with nicergoline, calcium hydrophosphate and magnesium stearate, directly tabletting, coating and carrying out aluminum-plastic packaging to obtain the nicergoline tablets. The nicergoline tablet prepared by the method provided by the invention can be rapidly and completely disintegrated, so that the aim of rapid dissolution is fulfilled.

Experiments prove that if the method provided by the invention is not adopted, the nicergoline tablet prepared by directly tabletting the nicergoline, the microcrystalline cellulose, the sodium carboxymethylcellulose, the calcium hydrophosphate and the magnesium stearate powder or by mixing the main drug and the auxiliary material together and then carrying out wet granulation cannot realize the purposes of quick disintegration and quick dissolution.

The invention provides a direct compression process of nicergoline tablets without traditional disintegrants, and nicergoline tablets prepared by the process provided by the invention are rapidly disintegrated and have good stability.

The microcrystalline cellulose and the sodium carboxymethylcellulose in the prescription are granulated, so that the prescription which cannot be completely disintegrated and is slowly dissolved is changed into the prescription which can be quickly and completely disintegrated and quickly dissolved. The method provided by the invention does not contain the traditional disintegrating agent, ensures the stability of the product, and realizes the rapid disintegration and dissolution of the nicergoline tablets.

The invention discloses a preparation method of a rapidly disintegrating nicergoline tablet, which mainly comprises the following steps:

step one

The preparation method comprises the specific steps of granulating microcrystalline cellulose and sodium carboxymethylcellulose in a prescription by adopting a wet granulation process, drying the prepared microcrystalline cellulose-sodium carboxymethylcellulose granules, and controlling the particle size of the dried granules to obtain the composite auxiliary material granules with the rapid disintegration property.

Step two

Mixing: mixing the prepared microcrystalline cellulose-sodium carboxymethyl cellulose particles, nicergoline, calcium hydrogen phosphate and magnesium stearate for a certain number of revolutions to obtain total mixed powder.

Step three

Tabletting: and (3) placing the prepared total mixed powder into a tabletting machine for tabletting, and monitoring related parameters to obtain the nicergoline tablets.

Step four

Coating: and (3) placing the prepared nicergoline tablets in a high-efficiency coating pot for film coating to obtain nicergoline coated tablets.

Step five

And (3) aluminum-plastic packaging: and packaging the nicergoline coated tablet to obtain a finished product. The package refers to an aluminum-plastic package and is made of PVC-aluminum or PVDC-PVC-aluminum.

The invention is further improved in that:

in the first step, the weight ratio of microcrystalline cellulose to sodium carboxymethyl cellulose is 10: 1-30: 1; the wet granulation process of the microcrystalline cellulose and the sodium carboxymethyl cellulose comprises a wet mixing granulation process and a boiling granulation process; drying the microcrystalline cellulose-sodium carboxymethyl cellulose particles by an oven and boiling, wherein the drying temperature is 30-70 ℃; the particle size of the microcrystalline cellulose-sodium carboxymethyl cellulose particles is controlled by adopting a sieve with 18-200 meshes to carry out size stabilization on the microcrystalline cellulose-sodium carboxymethyl cellulose particles.

The mixing in the second step comprises two steps of premixing and total mixing. The premixing is to mix microcrystalline cellulose-carboxymethyl cellulose sodium particles, nicergoline and calcium hydrophosphate; the total mixing is to add magnesium stearate into the premixed powder for total mixing.

The monitoring related parameters in the third step refer to the monitoring of the thickness, weight difference and hardness of the tablet in the tabletting process.

In the step four, the selected coating material is a film coating premix which comprises HPMC type and PVA type.

And in the fifth step, the aluminum-plastic package is made of PVDC-PVC-aluminum material.

The invention is further improved in that:

in the first step, the weight ratio of microcrystalline cellulose to sodium carboxymethyl cellulose is 15: 1-20: 1; selecting a wet mixing granulation process as the wet granulation process of the microcrystalline cellulose and the sodium carboxymethyl cellulose; drying the microcrystalline cellulose-carboxymethylcellulose sodium particles at the temperature of 40-60 ℃; the particle size of the microcrystalline cellulose-sodium carboxymethylcellulose particles is controlled by adopting a 24-100-mesh screen to carry out particle size stabilization on the microcrystalline cellulose-sodium carboxymethylcellulose particles.

The invention is further improved in that:

and in the step one, the grain size of the microcrystalline cellulose-sodium carboxymethyl cellulose particles is controlled by adopting a 40-80 mesh screen to carry out size stabilization on the microcrystalline cellulose-sodium carboxymethyl cellulose particles.

The film coating in the fourth step is HPMC type film coating premix, which mainly comprises the following components: HPMC, titanium dioxide, and polyethylene glycol.

Due to the adoption of the technical scheme, the technical progress of the invention is as follows:

(1) the invention provides a novel method for improving the disintegration of nicergoline tablets, and no report that microcrystalline cellulose and sodium carboxymethylcellulose are granulated so as to improve the disintegration is provided before the method. The microcrystalline cellulose-carboxymethylcellulose sodium particles prepared by the method can be used for other tablets needing to be quickly disintegrated besides the nicergoline tablets.

(2) The microcrystalline cellulose-carboxymethylcellulose sodium particles prepared by adopting the key steps have the main effects of quickly disintegrating the prepared nicergoline tablets in the prescription and also have the effects of an adhesive and a filler. Experiments prove that if the method provided by the invention is not adopted, the nicergoline tablet prepared by directly tabletting the nicergoline, the microcrystalline cellulose, the sodium carboxymethylcellulose, the calcium hydrophosphate and the magnesium stearate powder or by mixing the main drug and the auxiliary material together and then carrying out wet granulation cannot realize the purposes of quick disintegration and quick dissolution.

(3) The nicergoline tablet prepared by the technical scheme does not contain a traditional disintegrating agent, and the prepared nicergoline tablet is not easy to absorb moisture in the preparation process and the storage process and has good stability.

Drawings

Figure 1. dissolution profiles of examples and comparative examples in ph1.2 medium (n-6);

fig. 2. dissolution curves of examples and comparative examples in ph4.0 medium (n ═ 6);

fig. 3. dissolution curves of examples and comparative examples in ph6.8 medium (n-6);

the dissolution conditions used in the above dissolution curve examination were: the slurry method is implemented by 100 turns, 900ml of medium is sampled, 5ml of medium is sampled each time, and blank dissolution medium with the same volume is added after sampling. The detection method comprises the following steps: HPLC method, detection wavelength 288 nm.

Detailed Description

The invention will now be described in the following examples, which are intended to be illustrative only and not limiting to the scope of protection.

The raw materials and auxiliary materials used in the following examples are, unless otherwise specified, those which are generally commercially available. The main equipment used is a wet mixing granulator, manufacturer: shenzhen, Xinyite science and technology Limited, model: G10. rotary tablet press, manufacturer: shanghai information source pharmaceutical machinery ltd, model number: ZPS 8. Three-dimensional mixer, manufacturer: chat to Wanhe Industrial manufacturing Co., Ltd, model number: SBH-10. Small size coating machine, manufacturer: shanghai yellow sea medical testing instrument, type: BY 300A. Tablet hardness tester, manufacturer: tianjin, Tianda Tiankui science and technology Limited, model: YD-20 KZ. Intelligent disintegration tester, manufacturer: tianjin, Tianda Tiankui science and technology Limited, model: 2B-2E. Dissolution tester, manufacturer: tianjin, Tianda Tiankui science and technology Limited, model: RC8 MD. High performance liquid chromatograph, manufacturer: shimadzu, Kaisha, type: LC-2030C.

The prescription, the composition and the preparation process of the fast disintegrating nicergoline tablet comprise the following steps:

example 1

TABLE 1 example 1 prescription composition (10mg standard) in preparation of nicergoline tablets

Note: 1. the microcrystalline cellulose, the sodium carboxymethylcellulose and the purified water are added by 5 percent according to the prescription amount so as to offset the loss in the granulation process; 2. when the coating solution is prepared, 10% more is prepared to offset the loss in the coating process.

2. Preparation process

(1) Granulation of microcrystalline cellulose and sodium carboxymethylcellulose

And (3) granulating: weighing microcrystalline cellulose and sodium carboxymethylcellulose according to 105% of the formula amount, placing the weighed materials in a wet mixing granulator, setting the rotating speed of a stirring paddle and the rotating speed of a shearing paddle, starting the wet mixing granulator, and performing dry mixing for 2 minutes. And after the dry mixing time is up, keeping the wet mixing granulator in an open state, and clicking an atomization water adding button to atomize and add water. After the atomization and water addition are finished, the wet mixing granulator is kept in an open state, and granulation is continued for 2 minutes. And clicking a discharging button after the granulating time reaches the preset time, discharging, and closing the wet mixing granulator after the discharging is finished.

And (3) drying: uniformly spreading the prepared microcrystalline cellulose-carboxymethylcellulose sodium particles in a baking pan, placing in a drying oven, setting the temperature to be 40-60 ℃, starting timing when the temperature is reached, sampling about 1g every 0.5h after drying for 3.5h, measuring the moisture by using a rapid moisture tester, stopping drying after the requirements are met, closing the drying oven, and recording the drying time.

Straightening: the microcrystalline cellulose-carboxymethylcellulose sodium particles were sized using a screen of a selected mesh number, and the particles above the screen were pulverized so that all of them passed through the screen of the selected mesh number. After the whole grains are finished, the obtained microcrystalline cellulose-carboxymethyl cellulose sodium grains are placed in a clean material bag and sealed for later use.

(2) Mixing

Premixing: weighing the microcrystalline cellulose-carboxymethylcellulose sodium particles, the nicergoline and the calcium hydrophosphate in the prescription amount and placing the mixture in a mixer. And (4) covering the hopper cover, starting the mixer, and performing premixing operation, wherein the mixing revolution is 150-300 revolutions.

Total mixing: weighing magnesium stearate in a prescription amount, placing the magnesium stearate in a premixing mixer, covering a hopper cover, opening the mixing machine, and carrying out total mixing operation, wherein the mixing revolution is 100-200 revolutions. And discharging the total mixed particles in the mixer into a clean material bag, sampling, sealing, and taking out a sample to be used for measuring the total mixed powder content.

(3) Tabletting

The total mixed powder is added into a hopper of a tablet press at one time, the tablet press is started, the rotating speed of the tablet press is set to be 20rpm for tabletting operation, and the mouth of a clean material bag for containing tablets is tied on a discharge port of the tablet press by a silica gel elastic band in the tabletting process, so that the tablets are prevented from being exposed. Appearance, tablet weight and tablet thickness were monitored during the compression. Sampling and inspecting after tabletting. And after sampling, sealing the clean material bag filled with the plain sheets, placing the clean material bag in an aluminum-plastic composite bag, sealing, and storing the mark for later use.

(4) Coating film

Preparing a coating solution: weighing the film coating premix and purified water according to 110% of the formula amount, placing the coating premix in the purified water in a stirring state, quickly stirring to disperse formed lumps, reducing the stirring speed to almost eliminate vortex, and continuously stirring for 45 minutes for later use.

And (3) coating process: and installing the coating machine, and adjusting the pressure of compressed air to 0.05-0.3 mpa. Setting the rotating speed of the coating pan to be 15-25 rpm, setting the air inlet temperature to be 40-70 ℃, and adjusting the air inlet angle to ensure that the temperature of the slice bed is 40-55 ℃. Adding the plain tablets into a coating pot, starting a coating machine, preheating for 10-30 minutes, sampling, and weighing the tablets before coating. And setting the rotating speed of a peristaltic pump to enable the flow rate of the coating liquid to be 5-15 g/min, and coating. The appearance of the coated tablets was checked during the coating process. And after coating, closing the peristaltic pump, continuously drying for 10-30 minutes, sampling, weighing the coated tablets, and calculating the weight gain of the coating. And (5) sampling after coating is finished, and detecting the water content, the content and the dissolution curve. After the coated tablets are cooled, discharging into a clean plastic bag, and sealing.

(5) Plastic-aluminum package

And (3) aluminum-plastic packaging: and (3) installing an aluminum-plastic blister packaging machine, opening compressed air, starting a water cooling machine, setting the temperature of each heating plate to be 140 +/-20 ℃, setting the heat sealing temperature to be 180 +/-20 ℃, switching on a power supply, and preheating for 20-30 minutes. And (3) pouring tablets into a hopper, starting the host machine and the leakage detection device after the temperature of each heating plate reaches a set value, running the empty machine, and starting a blanking switch to work formally after determining that the bubble hole forming, the heat sealing, the batch number imprinting and the blanking are normal. After normal packaging, the quality is periodically checked and recorded. Unqualified tablets such as black spots, color spots, loose pieces, splinters and the like are removed at any time in the packaging process, and abnormal/unqualified aluminum-plastic tablets are removed. And after the packaging is finished, randomly taking the packaged sample, and detecting according to the internal control quality standard.

The following preparation processes of examples 2 to 5 were identical to those of example 1, and the formulation compositions were different.

Example 2

TABLE 2 example 2 prescription composition (5mg standard) in preparation of nicergoline tablets

Example 3

TABLE 3 example 3 prescription composition (30mg standard) in preparation of nicergoline tablets

Example 4

TABLE 4 example 4 prescription composition (10mg standard) in preparation of nicergoline tablets

Example 5

TABLE 5 example 5 prescription composition (10mg standard) in preparation of nicergoline tablets

Comparative example:

the samples of the comparative examples were prepared by a powder direct compression process and a wet granulation process, respectively.

Comparative example 1

TABLE 6 comparison example 1 prescription composition (10mg standard) in preparation of nicergoline tablets

Note: 1. when the coating solution is prepared, 10% more is prepared to offset the loss in the coating process.

Preparation process

(1) Mixing

Premixing: weighing nicergoline, microcrystalline cellulose, sodium carboxymethylcellulose and calcium hydrogen phosphate according to the prescription amount, and placing the materials in a mixer. And (4) covering the hopper cover, starting the mixer, and performing premixing operation, wherein the mixing revolution is 150-300 revolutions.

(2) Tabletting

(3) Coating film

(4) Plastic-aluminum package

The following comparative example 2 was prepared in accordance with comparative example 1.

Comparative example 2

TABLE 7 comparison example 2 prescription composition (10mg standard) in preparation of nicergoline tablets

Comparative example 3

TABLE 8 comparison example 3 prescription composition (10mg standard) in preparation of nicergoline tablets

Note: 1. the microcrystalline cellulose, the sodium carboxymethylcellulose, the calcium hydrophosphate and the purified water are all added by 5 percent according to the prescription amount so as to offset the loss in the granulation process; 2. when the coating solution is prepared, 10% more is prepared to offset the loss in the coating process.

Preparation process

(1) Wet granulation of auxiliary materials

And (3) granulating: weighing microcrystalline cellulose, sodium carboxymethylcellulose and calcium hydrogen phosphate according to 105% of the formula amount, placing the materials in a wet mixing granulator, setting the rotating speed of a stirring paddle and the rotating speed of a shearing paddle, starting the wet mixing granulator, and performing dry mixing for 2 minutes. And after the dry mixing time is up, keeping the wet mixing granulator in an open state, and clicking an atomization water adding button to atomize and add water. After the atomization and water addition are finished, the wet mixing granulator is kept in an open state, and granulation is continued for 5 minutes. And clicking a discharging button after the granulating time reaches the preset time, discharging, and closing the wet mixing granulator after the discharging is finished.

And (3) drying: uniformly spreading the prepared auxiliary material particles in a baking pan, placing the baking pan in a drying oven at the set temperature of 40-60 ℃, starting timing when the temperature reaches, sampling about 1g every 0.5h after drying for 4.0h, measuring the moisture by using a rapid moisture tester, stopping drying after the requirement is met, closing the drying oven, and recording the drying time.

Straightening: the granules of the auxiliary material are granulated with a sieve having a selected mesh number, and the granules above the sieve are pulverized so that all of them pass through the sieve having the selected mesh number. And after finishing the granulation, placing the obtained auxiliary material particles in a clean material bag, and sealing for later use.

(2) Mixing, (3) tabletting, (4) coating, and (5) plastic-aluminum packaging are the same as in example 1.

Comparative example 4

TABLE 9 comparative example 4 prescription composition (5mg size) in preparation of nicergoline tablets

Preparation process

(1) Wet granulation

And (3) granulating: weighing nicergoline, microcrystalline cellulose, sodium carboxymethylcellulose and calcium hydrogen phosphate according to the prescription amount, placing the nicergoline, the microcrystalline cellulose, the sodium carboxymethylcellulose and the calcium hydrogen phosphate in a wet mixing granulator, setting the rotating speed of a stirring paddle and the rotating speed of a shearing paddle, starting the wet mixing granulator, and performing dry mixing for 2 minutes. And after the dry mixing time is up, keeping the wet mixing granulator in an open state, and clicking an atomization water adding button to atomize and add water. After the atomization and water addition are finished, the wet mixing granulator is kept in an open state, and granulation is continued for 5 minutes. And clicking a discharging button after the granulating time reaches the preset time, discharging, and closing the wet mixing granulator after the discharging is finished.

Quality study

The samples prepared according to examples 1 to 5 and comparative examples 1 to 4 were tested according to established quality standards, in particular comparing the dissolution curves of the samples according to examples 1 to 5 and comparative examples 1 to 4 in different media.

TABLE 10 examination results of samples prepared in examples 1 to 5 and comparative example

It can be seen from the data in Table 10 that the samples of examples 1-5 prepared by the method provided by the present invention have significantly higher dissolution in media at pH6.8 than the samples prepared in comparative examples 1-4. Disintegration time period examination showed that the samples prepared in examples 1-5 all disintegrated completely and rapidly, while the samples in comparative example 1 and comparative example 2 did not disintegrate, and the samples in comparative example 3 and comparative example 4 did not disintegrate completely.

The samples prepared in examples 1 to 5 all disintegrated rapidly within 1min in the above 3 media, showing rapid dissolution. The samples of the comparative example 1 and the comparative example 2 are dissolved in the pH1.2 medium and the pH4.0 medium gradually because the calcium hydrophosphate in the formula is dissolved in the pH1.2 medium and the pH4.0 medium, the samples are slowly dissolved but not disintegrated, and the dissolution is slow; in the medium of pH6.8, calcium hydrogen phosphate did not dissolve, and the sample of the comparative example did not disintegrate and could not be dissolved. The samples of comparative examples 3 and 4 showed slow dissolution in the above 3 media, which were slow and incomplete in disintegration and no longer continued after disintegration into large pieces, and the amount of dissolution in the same time was significantly less than in the examples.

Claims

1. A preparation method of a fast disintegrating nicergoline tablet is characterized by comprising the following preparation steps:

a. the composite auxiliary material granules with the rapid disintegration property are prepared by a wet granulation process, and two auxiliary materials which do not have the rapid disintegration property in the prescription are granulated to ensure that the granules have the rapid disintegration property; the preparation process comprises the following steps: granulating microcrystalline cellulose and sodium carboxymethylcellulose in the formula by adopting a wet granulation process, wherein the weight ratio of the microcrystalline cellulose to the sodium carboxymethylcellulose is 10: 1-30: 1; drying the prepared microcrystalline cellulose-carboxymethylcellulose sodium particles, and controlling the particle size of the dried particles to obtain composite auxiliary material particles with quick disintegration property;

b. mixing the composite auxiliary material particles with the main medicine and other auxiliary materials, and tabletting; wherein the main drug is nicergoline, the other accessories are calcium hydrogen phosphate and magnesium stearate, and the tabletting process is a powder direct compression process.

2. The preparation method according to claim 1, wherein the weight ratio of the microcrystalline cellulose to the carboxymethylcellulose sodium is 15:1 to 20: 1.

3. The preparation method as set forth in claim 1, wherein the microcrystalline cellulose and sodium carboxymethylcellulose wet granulation process comprises a wet mixing granulation process and an ebullient granulation process.

4. The preparation method according to claim 1, wherein the drying of the microcrystalline cellulose-carboxymethylcellulose sodium particles comprises oven drying and boiling drying, and the drying temperature is 30-70 ℃.

5. The preparation method according to claim 1, wherein the microcrystalline cellulose-carboxymethylcellulose sodium particle drying comprises oven drying and boiling drying, and the drying temperature is 40-60 ℃.

6. The production method according to claim 1, wherein the particle size of the microcrystalline cellulose-carmellose sodium particles is controlled by granulating the microcrystalline cellulose-carmellose sodium particles with a 18-200 mesh screen.

7. The production method according to claim 1, wherein the particle size of the microcrystalline cellulose-carmellose sodium particles is controlled by granulating the microcrystalline cellulose-carmellose sodium particles with a 24-100 mesh screen.

8. The production method according to claim 1, wherein the particle size of the microcrystalline cellulose-carmellose sodium particles is controlled by granulating the microcrystalline cellulose-carmellose sodium particles with a 40-80 mesh screen.

9. A preparation method of a fast disintegrating nicergoline tablet comprises the following preparation steps:

(1) the composite auxiliary material granules with the rapid disintegration property are prepared by a wet granulation process, and two auxiliary materials which do not have the rapid disintegration property in the prescription are granulated to ensure that the granules have the rapid disintegration property; the preparation process comprises the following steps: granulating microcrystalline cellulose and sodium carboxymethylcellulose in a prescription by adopting a wet granulation process, drying the prepared microcrystalline cellulose-sodium carboxymethylcellulose granules, and controlling the particle size of the dried granules to obtain composite auxiliary material granules with quick disintegration performance;

(2) mixing: mixing the prepared microcrystalline cellulose-carboxymethylcellulose sodium granules, nicergoline, calcium hydrogen phosphate and magnesium stearate to obtain total mixed powder; the mixing comprises two steps of premixing and total mixing, wherein the premixing comprises the step of mixing microcrystalline cellulose-sodium carboxymethyl cellulose particles, nicergoline and calcium hydrophosphate, and the total mixing is the step of adding magnesium stearate into premixed powder for total mixing;

(3) tabletting: putting the total mixed powder prepared in the step (2) into a tabletting machine, and tabletting to obtain nicergoline tablets;

(4) coating: putting the prepared nicergoline tablets in a high-efficiency coating pot for film coating to obtain nicergoline coated tablets; the film coating is characterized in that the selected coating material is a film coating premix comprising HPMC type and PVA type;

(5) and (3) aluminum-plastic packaging: and packaging the nicergoline coated tablet to obtain a finished product, wherein the package is an aluminum-plastic blister package which is made of PVC-aluminum or PVDC-PVC-aluminum.