CN115634205A

CN115634205A - Acetylcysteine granules and preparation method thereof

Info

Publication number: CN115634205A
Application number: CN202211443283.8A
Authority: CN
Inventors: 雷文枚; 孙关军; 杨希; 张瑜
Original assignee: HUNAN PUDAO MEDICAL TECHNOLOGY CO LTD; Hunan Jiudian Pharmaceutical Co Ltd
Current assignee: HUNAN PUDAO MEDICAL TECHNOLOGY CO LTD; Hunan Jiudian Pharmaceutical Co Ltd
Priority date: 2022-11-18
Filing date: 2022-11-18
Publication date: 2023-01-24
Anticipated expiration: 2042-11-18
Also published as: CN115634205B

Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a pharmaceutical composition containing acetylcysteine, which comprises acetylcysteine with the particle size of 200-600 mu m and blank particles with the particle size of 200-1000 mu m.

Description

Acetylcysteine granules and preparation method thereof

Technical Field

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to acetylcysteine particles and a preparation method thereof.

Background

Acetylcysteine (Acetylcysteine) is a mucus dissolving agent and has a strong phlegm dissolving effect. The sulfhydryl contained in the molecule can break the disulfide bond in glycoprotein polypeptide chain in the sputum, thereby reducing the viscosity of the sputum and leading the sputum to be liquefied and easy to expectorate. Is suitable for respiratory system diseases characterized by excessive viscous secretion, such as COPD, bronchiectasis, etc.

The structural formula of acetylcysteine is as follows:

。

the acetylcysteine contains hydrophobic groups in the molecular structure, so that the acetylcysteine is unstable in chemical property, easy to generate oxidation reaction and sensitive to damp heat. Therefore, the acetylcysteine oral solid preparation has poor stability of the raw material drug acetylcysteine, and the curative effect of the acetylcysteine is seriously influenced.

Patent CN110507618A discloses acetylcysteine granules and a preparation method thereof, wherein auxiliary materials comprise a filler, menthol, a flavoring agent and essence, the preparation method adopts a fluidized bed one-step granulation method, and the menthol is used as a stabilizer to improve the stability of the acetylcysteine granules. Patent CN102743369A discloses a pharmaceutical composition of acetylcysteine, which is added with an auxiliary material glidant to solve the problems that acetylcysteine is easy to aggregate and not easy to mix uniformly, and the coating effect of the glidant reduces the moisture absorption and degradation of the active ingredient acetylcysteine and improves the stability of the pharmaceutical composition. Patent CN102144978A discloses acetylcysteine granules and a preparation process thereof, the preparation method is that acetylcysteine is coated by acrylic resin and then mixed with other auxiliary materials, and the preparation method improves the stability of the granules. However, the acrylic resin coating uses organic reagents, which involves the problems of the use of the organic reagents and the residue of the organic reagents, and the industrial production has high requirements on production equipment and operation.

The prior art methods described above have attempted various means to improve the stability of acetylcysteine drugs, but all have certain problems. Patent document 1 (CN 110507618A) uses menthol to improve the stability of the preparation, the menthol has certain irritation, adverse drug reactions possibly caused by oral administration of the menthol include irritation to gastrointestinal tract and discomfort such as nausea and vomiting, and excessive development of central nerves of children, and sleepiness, dyspnea and even coma may occur, so that children are not clinically recommended to use the menthol. Patent document 2 (CN 102743369A) uses glidant silicon dioxide or talc powder to promote mixing of raw and auxiliary materials, both silicon dioxide and talc powder are water-insoluble auxiliary materials, and the mixture is taken with water to have a mouth feel similar to fine sand, so that the mouth feel is poor, and patients with small ages are not easy to accept, and the compliance of the patients is affected. Patent document 3 (CN 102144978A) adopts acrylic resin to coat acetylcysteine, uses organic solvent, has a complex process and is not environment-friendly, and adopts acrylic resin to coat acetylcysteine powder, which is prone to cause the problem of film coating stickiness, and the film coating forms larger particles after being adhered with other auxiliary materials, thus affecting the dispersion uniformity of the granules.

The acetylcysteine granules are expectorants, and are mainly taken by children who belong to special people, and stabilizers, glidants and the like are not suitable to be added. Because acetylcysteine is unstable, the active ingredient proportion in the preparation is very small, the mixing uniformity of raw and auxiliary materials is difficult to control in production, and the content uniformity and the treatment effectiveness of the preparation are further influenced.

Disclosure of Invention

The invention aims to provide the acetylcysteine granules which do not contain a stabilizer and a glidant, have simple preparation process and good content uniformity and are stable for a long time.

It is another object of the present invention to provide a method for preparing the above particles.

A pharmaceutical composition comprises effective amount of acetylcysteine and blank particles, wherein the acetylcysteine is characterized in that the proportion of the acetylcysteine with the particle size within the range of 200 mu m-600 mu m is 80% -100%, and the blank particles are characterized in that the proportion of the blank particles with the particle size within the range of 200 mu m-1000 mu m is 60% -100%. The pharmaceutical composition comprises 100-200 parts of acetylcysteine and 1300-1600 parts of blank granules.

It has been found that the mixing uniformity of the pharmaceutical composition can be improved under the control of the composition and particle size of the material.

In the invention, the blank particles contain water-soluble polyhydroxy compound and fruit powder. Wherein the water-soluble polyhydroxy compound is one or more of lactose, sucrose, sorbitol or glucose. The fruit powder is one or more of orange juice powder, grapefruit fruit powder, lemon fruit powder, sweet orange juice powder, blueberry fruit powder, grape fruit powder, apple fruit powder or orange fruit powder. The blank particles comprise 1270 to 1415 parts of water-soluble polyhydroxy compound and 70 to 120 parts of fruit powder by weight.

In the invention, other auxiliary ingredients can be added into the pharmaceutical composition according to the preparation needs, and the auxiliary ingredients include but are not limited to at least one of flavoring agents, essences, coloring agents and the like. Wherein, the flavoring agent can be a commonly known flavoring component in the industry, such as saccharin sodium, aspartame, stevia rebaudiana and the like. The essence is well known in the industry, such as various fruit essences and the like. The colorant is a common colorant and can be a natural pigment or a synthetic pigment.

In the invention, the pharmaceutical composition can be further prepared into a pharmaceutical preparation. Preferably, the pharmaceutical formulation is a granule. Preferably, the granules comprise the following ingredients in parts by weight:

100 to 200 parts of acetylcysteine;

70 to 120 parts of fruit powder;

1270 to 1415 parts of sucrose I;

1280 to 1415 parts of sucrose II.

The shapes of the raw materials and the auxiliary materials are different, for example, blank particles, acetylcysteine and sucrose crystals are respectively in a nearly spherical shape, a needle shape and a square shape, and the mixing uniformity is poor.

The invention provides two preparation methods of granules, which are respectively a scheme I and a scheme II.

The first scheme is a preparation process of uniformly mixing acetylcysteine and blank particles and then quantitatively adding cane sugar. In the first scheme, the sucrose I is sucrose powder obtained by crushing sucrose and then sieving the crushed sucrose with a 80-mesh sieve for pretreatment; the sucrose II is sucrose crystal.

Taking acetylcysteine granules as an example, according to the first scheme, the preparation process comprises the following steps:

(1) Weighing raw and auxiliary materials according to the prescription composition, mixing fruit powder and sucrose powder, granulating, drying and screening to obtain blank granules;

(2) Uniformly mixing the blank particles and acetylcysteine by a progressive method to obtain a component A;

(3) Adding the component A and the sucrose crystals into a packaging bag according to the proportion of the prescription to obtain the acetylcysteine granules.

Preferably, according to scheme one, the preparation process of the acetylcysteine granules comprises the following steps:

(1) Weighing raw and auxiliary materials according to the formula, mixing sweet orange juice powder with sucrose powder, adding saccharin sodium and sunset yellow, performing wet granulation, drying, screening and finishing granules, and collecting granules with the particle size meeting the requirement to obtain blank granules;

(2) Uniformly mixing the blank particles, acetylcysteine and fresh orange juice essence by a progressive method to obtain a component A;

Further preferably, the granules prepared in the first embodiment comprise the following components in parts by weight:

100 to 200 parts of acetylcysteine;

100 to 120 parts of sweet orange juice powder;

1270 to 1400 parts of sucrose powder;

1280 to 1400 parts of sucrose crystals;

0 to 7.1 parts of saccharin sodium;

0 to 0.5 portion of sunset yellow;

0 to 3 parts of fresh orange juice essence.

And in the second scheme, a preparation process for uniformly mixing acetylcysteine, blank particles and sucrose crystals is adopted. In the second scheme, the sucrose I is sucrose powder obtained by crushing sucrose and then sieving the crushed sucrose with a 80-mesh sieve for pretreatment; the sucrose II is sucrose crystal which is characterized in that the proportion of the sucrose crystal with the grain diameter of 200-850 mu m is 80-100%.

Taking acetylcysteine granules as an example, according to the second scheme, the preparation process comprises the following steps:

(1) Weighing raw and auxiliary materials according to the prescription amount, mixing fruit powder and sucrose powder, granulating, drying and screening to obtain blank granules;

(2) And uniformly mixing the blank particles, the acetylcysteine and the sucrose crystals by a progressive method, and subpackaging to obtain the acetylcysteine particles.

Preferably, according to scheme two, the preparation process of the acetylcysteine granules comprises the following steps:

(2) Uniformly mixing the blank particles, the acetylcysteine, the sucrose crystals and the rest auxiliary components by a progressive method, and subpackaging to obtain the acetylcysteine particles.

Still more preferably, the granule prepared in the second embodiment comprises the following components in parts by weight:

100 to 200 parts of acetylcysteine;

70 to 100 portions of sweet orange juice powder;

1350-1415 parts of sucrose powder;

1345 to 1415 parts of sucrose crystals;

0 to 6.5 parts of saccharin sodium;

0 to 0.5 part of sunset yellow;

0 to 3.4 parts of fresh orange juice essence.

The research finds that the content uniformity and stability of the preparation can be further improved by further combining and controlling the components, the particle size and the preparation process.

Advantageous effects

1. In the technical scheme of the invention, as the active ingredient acetylcysteine is unstable to moist heat, a blank particle is obtained by separately granulating part of auxiliary materials, and the dried blank particle is mixed with acetylcysteine and other auxiliary materials, so that the stability of the active ingredient acetylcysteine is improved, and the effectiveness and the safety of the medicament are ensured.

2. Compared with acetylcysteine, blank particles have large particle size and proportion difference, and the mixing uniformity is difficult to control. The invention further improves the content uniformity of the preparation by the combined control of the components, the particle size and the preparation process.

3. The preparation process is simple and feasible, and the prepared preparation has stable and controllable quality and is beneficial to industrial large-scale production.

Drawings

FIG. 1 is a flow chart of production processes in examples 1 to 7.

FIG. 2 is a flow chart of preparation processes in examples 8 to 16.

Detailed description of the preferred embodiments

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail by way of examples, which are provided for illustration only and do not represent the scope of the present invention defined by the claims.

The reagents and raw materials used in the invention are commercially available.

Controlling the particle size of the particles: referring to the double-screening method in the second method of 0982 [ particle size and particle size distribution determination method ] in the four ministry of general regulations in the 'Chinese pharmacopoeia' 2020 edition, particles or powder which can pass through a large-aperture sieve and cannot pass through a small-aperture sieve are taken, the weight is weighed, and the proportion (%) occupied by the particles is calculated as the particle size control limit.

And (3) content uniformity determination: according to the acetylcysteine particles [ content determination ] in the second part of the 'Chinese pharmacopoeia' 2020 edition, the method is used for determining (general rule 0512). Taking 1 bag of the product, transferring the total amount of the content into a 200ml measuring flask, adding an appropriate amount of sodium metabisulfite solution (1 → 2000), shaking to dissolve and dilute to scale, filtering, taking the subsequent filtrate as a test solution, taking an appropriate amount of acetylcysteine reference substance, precisely weighing, adding sodium metabisulfite solution (1 → 2000), dissolving and diluting to obtain a solution containing 0.5mg per 1ml as a reference solution. Octadecylsilane chemically bonded silica is used as a filling agent; with 0.05mol/L dipotassium hydrogen phosphate solution (pH adjusted to 3.0 with phosphoric acid) -methanol (90); the detection wavelength is 214nm; the injection volume was 20. Mu.l. The number of theoretical plates is not less than 2000 calculated by acetylcysteine peak. Precisely measuring the test solution and the reference solution, respectively injecting into a liquid chromatograph, and recording the chromatogram. The peak area of acetylcysteine is calculated according to an external standard method.

Referring to 0941 (content uniformity inspection method) of the general rules of the four departments in the 2020 edition of Chinese pharmacopoeia, it is concluded that the content uniformity of the product A +2.2S is less than or equal to L (L = 15.0), and the content uniformity of the sample meets the specification.

。

The specific embodiment of the invention is as follows:

example 1

1. Prescription composition

。

2. Particle size parameter of raw and auxiliary materials

Acetylcysteine particle size: the proportion of particles with the particle size of 200-600 mu m is 80.15%;

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 60.29%.

3. Preparation process

(1) The sucrose I is sucrose powder, and the sucrose II is sucrose crystal. Weighing raw and auxiliary materials according to the prescription amount, mixing sweet orange juice powder and sucrose powder in a wet granulator, adding a wetting agent for granulation, drying wet granules in a fluidized bed, and sieving to obtain empty and white granules.

(2) And (3) uniformly mixing the blank particles and acetylcysteine by a progressive method to obtain a component A, wherein the rotation speed is 10 to 15 rpm, and the rotation speed is 2 to 15min/time.

(3) Adding the component A and the sucrose crystals into a packaging bag according to the proportion of the formula to obtain the acetylcysteine particles.

Example 2

1. The formulation and preparation process are the same as in example 1.

2. The particle size parameters of the raw materials and auxiliary materials are as follows:

particle size of the blank particles: 200 to 1000 μm.

Example 3

1. The formulation and preparation process are the same as in example 1.

2. The particle size parameters of the raw materials and the auxiliary materials are as follows:

acetylcysteine particle size: the proportion of particles with the particle size of 200-600 mu m is 90.46 percent;

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.20%.

Example 4

1. The formulation and preparation process are the same as in example 1.

acetylcysteine particle size: 200-600 μm;

Example 5

1. The formulation and preparation process are the same as in example 1.

acetylcysteine particle size: 200-600 μm;

particle size of the blank particles: 200 to 1000 μm.

Example 6

1. Prescription composition

。

2. Particle size parameter of raw and auxiliary materials

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.11%.

3. Preparation process

(1) The sucrose I is sucrose powder, and the sucrose II is sucrose crystal. Weighing raw and auxiliary materials according to the prescription amount, mixing the sweet orange juice powder and the sucrose powder in a wet granulator, adding a wetting agent into the mixture by taking an aqueous solution containing saccharin sodium and sunset yellow as the wetting agent for granulation, drying the wet granules in a fluidized bed, and sieving to obtain empty and white granules.

(2) And (3) mixing the blank particles, acetylcysteine and fresh orange juice essence by a progressive method to obtain a component A, wherein the rotating speed is 10 to 15 rpm and 2 to 15min/time.

Example 7

1. Prescription composition

。

2. Particle size parameter of raw and auxiliary materials

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.32%.

3. The preparation process is the same as in example 6

The prescription compositions of examples 1-7 are shown in Table 1, and the particle size parameters of the raw and auxiliary materials are shown in Table 2.

TABLE 1 formulation compositions of examples 1 to 7

。

TABLE 2 particle diameter parameters of the raw and auxiliary materials in examples 1 to 7

。

The content uniformity detection data of the samples of examples 1 to 7 are as follows:

。

and (4) summarizing: in examples 1 to 7, the influence of acetylcysteine and blank particles with different particle sizes on the content uniformity was examined by using a preparation process (scheme one) in which acetylcysteine and blank particles are uniformly mixed and then a sucrose crystal is quantitatively added. The content uniformity A +2.2S of the sample is not more than 15, and the content uniformity meets the requirement, which shows that the content uniformity of the self-made sample is good by controlling the proportion of acetylcysteine particles ranging from 200 mu m to 600 mu m to be not less than 80%, the proportion of blank particles ranging from 200 mu m to 1000 mu m to be not less than 60%, and the mixing uniformity of acetylcysteine and blank particles is good. By adopting the preparation process, the content uniformity of the preparation meets the requirement and the repeatability is good.

Example 8

1. Prescription composition

。

2. Particle size parameter of raw and auxiliary materials

Acetylcysteine particle size: the proportion of particles with the particle size of 200-600 mu m is 90.23%;

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.42%;

the grain size of the sucrose crystals is: 200 to 850 μm.

3. Preparation process

(1) The sucrose I is sucrose powder, and the sucrose II is sucrose crystal. Weighing raw and auxiliary materials according to the formula amount, mixing the sweet orange juice powder and the sucrose powder in a wet granulator, adding a wetting agent for granulation, drying the wet granules in a fluidized bed, and sieving to obtain blank granules.

(2) And (3) mixing the blank particles, the acetylcysteine and the sucrose crystals uniformly by a progressive method, wherein the rotation speed is 10 to 15 rpm, and 2 to 15min/time.

(3) And (5) subpackaging the granules to obtain the acetylcysteine granules.

Example 9

1. The formulation and preparation process were the same as in example 8.

the grain size of the sucrose crystals is: the proportion of particles with the particle size of 200-850 mu m is 90.19%.

Example 10

1. The formulation and preparation process were the same as in example 8.

the grain size of the sucrose crystals is: the proportion of particles with the particle size of 200-850 mu m is 80.07%.

Example 11

1. The formulation and preparation process were the same as in example 8.

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 60.38%;

the grain size of the sucrose crystals is: 200 to 850 μm.

Example 12

1. The formulation and preparation process were the same as in example 8.

Example 13

1. The formulation and preparation process were the same as in example 8.

acetylcysteine particle size: 200-600 μm;

particle size of the blank particles: 200-1000 μm;

the grain size of the sucrose crystals is as follows: 200 to 850 μm.

Example 14

The formulation and preparation process were the same as in example 8.

The particle size parameters of the raw materials and auxiliary materials are as follows:

acetylcysteine particle size: 200-600 μm;

particle size of the blank particles: 200-1000 μm;

the grain size of the sucrose crystals is as follows: the proportion of particles with the particle size of 200-850 mu m is 80.07%.

Example 15

1. The prescription composition is shown in the following table:

。

2. particle size parameter of raw and auxiliary materials

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.34%;

3. Preparation process

(1) The sucrose I is sucrose powder, and the sucrose II is sucrose crystal. Weighing raw and auxiliary materials according to the prescription amount, mixing sweet orange powder and sucrose powder in a wet granulator, adding a wetting agent into the mixture by taking an aqueous solution containing saccharin sodium and sunset yellow as the wetting agent for granulation, drying wet granules in a fluidized bed, and sieving to obtain blank granules.

(2) Uniformly mixing the blank particles, acetylcysteine, sucrose crystals and fresh orange juice essence by a gradual addition method, wherein the rotation speed is 10 to 15 rpm and 2 to 15min/time.

(3) And (5) subpackaging the granules to obtain the acetylcysteine granules.

Example 16

1. Prescription composition

。

2. Particle size parameter of raw and auxiliary materials

particle size of the blank particles: the proportion of particles with the particle size of 200-1000 μm is 80.26%;

3. The preparation process was the same as in example 15.

The formulation compositions of examples 8 to 16 are shown in Table 3, and the particle diameter parameters of the raw and auxiliary materials are shown in Table 4.

TABLE 3 prescription compositions of examples 8 to 16

。

TABLE 4 particle diameter parameters of raw and auxiliary materials in examples 8 to 16

。

The content uniformity detection data of the samples of examples 8 to 16 are as follows:

。

and (3) knotting: in examples 8 to 16, a preparation process (scheme two) in which acetylcysteine, blank particles, and sucrose crystals are uniformly mixed is adopted, and the influence of acetylcysteine, blank particles, and sucrose crystals with different particle sizes on the content uniformity is examined. The content uniformity A +2.2S of the sample is not more than 15, and the content uniformity A +2.2S of the sample meets the requirement, which shows that the content uniformity of the prepared preparation meets the requirement and has good repeatability by controlling the proportion of acetylcysteine with the particle size of 200-600 mu m to be not less than 80%, the proportion of blank particles with the particle size of 200-1000 mu m to be not less than 60%, and the proportion of sucrose crystal with the particle size of 200-850 mu m to be not less than 80%.

Comparative example 1

The formulation and preparation process were the same as in example 2. Compared with the embodiment 2, the difference is only in the particle size parameter of the raw and auxiliary materials, and the proportion of the acetylcysteine particles with the particle size of 200-600 mu m is 70.49%.

Comparative example 2

The formulation and preparation process were the same as in example 4. Compared with the embodiment 4, the difference is only in the parameters of the particle size of the raw and auxiliary materials, and the proportion of the particles with the particle size of the blank particles ranging from 200 mu m to 1000 mu m is 50.21%.

Comparative example 3

The formulation and preparation process were the same as in example 10. Compared with the particle size parameters of the raw materials and the auxiliary materials in the embodiment 10, the difference is only that the proportion of the particles with the sucrose crystal particle size of 200-850 mu m is 70.37%.

TABLE 5 formulation compositions for comparative examples 1 to 3

。

TABLE 6 particle size parameters of the raw and auxiliary materials in comparative examples 1 to 3

。

The content uniformity test data of the samples of comparative examples 1 to 3 are shown in the following table.

TABLE 7 content uniformity of comparative examples 1-3

。

As can be seen from comparative examples 1 and 2, the preparation process (scheme I) of uniformly mixing acetylcysteine and blank particles and then quantitatively adding sucrose is adopted, and when the proportion of the acetylcysteine particles with the particle sizes of 200-600 μm is 70%, or the proportion of the blank particles with the particle sizes of 200-1000 μm is 50%, the content uniformity of the sample is not qualified.

As can be seen from the comparative example 3, by adopting the preparation process (scheme II) in which acetylcysteine, blank particles and sucrose crystals are uniformly mixed, when the proportion of the sucrose crystal particle size range of 200-850 μm is 70%, the content uniformity of the sample is unqualified.

From comparative analysis of examples 1 to 5 and comparative examples 1 to 2, and examples 8 to 14 and comparative example 3, it can be seen that:

according to the first scheme, the proportion of acetylcysteine particles ranging from 200 micrometers to 600 micrometers is controlled to be more than or equal to 80%, and the proportion of blank particles ranging from 200 micrometers to 1000 micrometers is controlled to be more than or equal to 60%; and in the second scheme, the proportion of the acetylcysteine particles in the range of 200-600 microns is controlled to be more than or equal to 80%, the proportion of the blank particles in the range of 200-1000 microns is controlled to be more than or equal to 60%, the proportion of the sucrose crystals in the range of 200-850 microns is controlled to be more than or equal to 80%, the content uniformity of the sample meets the requirement, and the repeatability is good. If the particle size of the material exceeds the above-mentioned limit, there is a problem of non-uniformity of the content of the formulation, and the particle size of the material is a high risk factor causing the non-uniformity of the content of the formulation.

To further illustrate the advantageous effects of the present invention, the present invention provides the following test examples.

Test example 1

The stability of the home-made samples and the commercial products (proflavia, hanbang, hainan) of examples 3 and 10 according to the present invention was investigated.

The home-made samples and commercial products (Hainan Zanbang Fulu Shi) in examples 3 and 10 were selected and placed under stability conditions (accelerated conditions: temperature 40 ℃. + -. 2 ℃; humidity 75% ± 5 RH) for comparative investigation for 6 months, and then sampled at the beginning (or 0 month), 1 month, 2 months, 3 months and 6 months, respectively, according to the determination of acetylcysteine particles [ related substances ] in the second part of the "Chinese pharmacopoeia" 2020 edition [ acidity ] item, by the method.

TABLE 8 data on substance detection

。

Research results show that during the stability investigation period of 6 months between the self-made samples in the embodiment 3 and the embodiment 10 and the market products, the drying weight loss and the acidity data of the self-made samples are basically consistent with those of the market products, and the quality requirements are met; the self-made sample has slower growth compared with the commercial product. The self-made sample has good stability.

Claims

1. A pharmaceutical composition comprises 100 to 200 parts of acetylcysteine and 1300 to 1600 parts of blank particles, wherein the acetylcysteine and the blank particles are respectively 100 to 200 parts by weight, and the pharmaceutical composition is characterized in that the acetylcysteine with the particle size of 200 to 600 mu m accounts for 80 to 100 percent, and the blank particles with the particle size of 200 to 1000 mu m accounts for 60 to 100 percent.

2. The pharmaceutical composition according to claim 1, wherein the blank particles comprise 1270 to 1415 parts of water-soluble polyol and 70 to 120 parts of fruit powder.

3. The pharmaceutical composition of claim 2, wherein the water-soluble polyol is selected from one or more of lactose, sucrose, sorbitol and glucose, and the fruit powder is selected from one or more of orange juice powder, grapefruit fruit powder, lemon fruit powder, sweet orange juice powder, blueberry fruit powder, grape fruit powder, apple fruit powder and orange fruit powder.

4. Acetylcysteine granules which are further prepared from the pharmaceutical composition according to any one of claims 1 to 3.

5. Acetylcysteine particles according to claim 4, comprising the following ingredients, in parts by weight:

100 to 200 parts of acetylcysteine;

70 to 120 parts of fruit powder;

1270 to 1415 parts of sucrose I;

1280 to 1415 parts of sucrose II.

6. The acetylcysteine granules according to claim 5, wherein sucrose I is sucrose powder and sucrose II is sucrose crystals.

7. The acetylcysteine granules according to claim 6, wherein the sucrose II contains 80-100% of sucrose crystals with a particle size of 200-850 μm.

8. A process for the preparation of a pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition is obtained by mixing acetylcysteine and blank granules by the additive method.

9. A process for the preparation of acetylcysteine particles according to claim 6, comprising the steps of:

(1) Weighing raw and auxiliary materials according to the formula, mixing the fruit powder with the sucrose I, granulating, drying and screening to obtain blank granules;

(2) Uniformly mixing the blank particles obtained in the step (1) and acetylcysteine by a progressive method to obtain a component A;

(3) Adding the component A and the sucrose II into a medicine packaging bag according to the proportion of the prescription to obtain the acetylcysteine granules.

10. A process for the preparation of acetylcysteine particles according to claim 7, comprising the steps of:

(2) And (3) uniformly mixing the blank particles obtained in the step (1), acetylcysteine and sucrose II by a progressive method to obtain acetylcysteine particles.