CN115634205B - Acetylcysteine particles and preparation method thereof - Google Patents
Acetylcysteine particles and preparation method thereof Download PDFInfo
- Publication number
- CN115634205B CN115634205B CN202211443283.8A CN202211443283A CN115634205B CN 115634205 B CN115634205 B CN 115634205B CN 202211443283 A CN202211443283 A CN 202211443283A CN 115634205 B CN115634205 B CN 115634205B
- Authority
- CN
- China
- Prior art keywords
- acetylcysteine
- sucrose
- particles
- parts
- particle size
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
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 microns and blank particles with the particle size of 200-1000 microns, wherein the pharmaceutical composition can be further prepared into a preparation, and the problems of poor stability and poor content uniformity of the preparation are solved by matching the particle size control of raw and auxiliary materials with a specific production process.
Description
Technical Field
The application belongs to the technical field of pharmaceutical preparations, and in particular relates to acetylcysteine granules and a preparation method thereof.
Background
Acetylcysteine (Acetylcysteine) is a mucolytic agent and has a strong mucolytic effect. The sulfhydryl contained in the molecule can break disulfide bonds in glycoprotein polypeptide chains in sputum, thereby reducing the viscosity of the sputum and liquefying the sputum to facilitate expectoration. Is suitable for respiratory diseases characterized by excessive viscous secretion, such as COPD, bronchiectasis, etc.
The structural formula of acetylcysteine is as follows:
the acetylcysteine has unstable chemical property due to the inclusion of the hydrophobic group in the molecular structure, is easy to generate oxidation reaction and is sensitive to damp and heat. Therefore, the stability of the raw material medicine acetylcysteine in the acetylcysteine oral solid preparation is poor, and the curative effect of the acetylcysteine is seriously affected.
Patent CN110507618A discloses an acetylcysteine granule and a preparation method thereof, wherein auxiliary materials comprise filler, menthol, corrective and essence, and the preparation method adopts a fluidized bed one-step granulation method, wherein the menthol is used as a stabilizer to improve the stability of the acetylcysteine granule. Patent CN102743369a discloses a pharmaceutical composition of acetylcysteine, which solves the problem that acetylcysteine is easy to aggregate and difficult to mix evenly by adding auxiliary materials of glidants, and simultaneously, the coating effect of the glidants reduces the moisture absorption and degradation of the active ingredient acetylcysteine, and improves the stability of the pharmaceutical composition. Patent CN102144978A discloses an acetylcysteine granule and a preparation process thereof, wherein the preparation method adopts acrylic resin to coat acetylcysteine and then mix with other auxiliary materials, and the preparation method improves the stability of the granule. However, the acrylic resin coating is applied to organic reagents, which relates to the use problem of the organic reagents and the problem of organic reagent residues, and has high requirements on production equipment and operation in industrial production.
The above prior art methods have attempted to improve the stability of the p-acetylcysteine drug by various means, but all have certain problems. The menthol used in patent document 1 (CN 110507618A) improves the stability of the preparation, the menthol has a certain irritation, and adverse drug reactions possibly caused by taking the menthol orally include discomfort such as nausea and vomiting, and the like, and the central nervous system of children is not fully developed, and the children are possibly sleepy, dyspnea and even coma, so that the children are not suggested to use clinically. In patent document 2 (CN 102743369 a), the glidant silicon dioxide or talcum powder is used to promote the mixing of raw materials and auxiliary materials, the silicon dioxide and the talcum powder are water-insoluble auxiliary materials, and the water-flush administration has a taste similar to fine sand, has poor taste, is not easy to accept by patients with smaller ages, and affects the compliance of the patients. Patent document 3 (CN 102144978A) uses an acrylic resin to coat acetylcysteine, an organic solvent is used, the process is complex and not environment-friendly, and the coating of acetylcysteine powder by using an acrylic resin is easy to cause the problem of stickiness of a film coating, and the film coating and other auxiliary materials are adhered to form larger particles, so that the dispersion uniformity of the granules is affected.
The acetylcysteine particles are expectorants, the drug application population is mainly children, the children belong to special population, and stabilizers, glidants and the like are not suitable to be added. Because acetylcysteine is unstable, the active ingredient ratio in the preparation is small, and the mixing uniformity of raw materials and auxiliary materials is difficult to control in production, so that the content uniformity and the treatment effectiveness of the preparation are affected.
Disclosure of Invention
The invention aims to provide the acetylcysteine granules which do not contain stabilizing agents and glidants, have simple preparation process and good content uniformity and are stable for a long time.
It is a further object of the present invention to provide a process for preparing the above particles.
A pharmaceutical composition comprising an effective amount of acetylcysteine characterized in that the acetylcysteine has a particle size in the range of 200 μm to 600 μm is 80% to 100% and blank particles characterized in that the blank particles have a particle size in the range of 200 μm to 1000 μm is 60% to 100%. The pharmaceutical composition comprises 100-200 parts of acetylcysteine and 1300-1600 parts of blank particles.
It was found that the uniformity of mixing of the pharmaceutical composition can be improved under the composition and particle size control of the materials.
In the invention, the blank particles contain water-soluble polyhydroxy compounds 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 powder, lemon fruit powder, sweet orange juice powder, blueberry fruit powder, grape fruit powder, apple fruit powder and orange fruit powder. The blank particles contain 1270-1415 parts by weight of water-soluble polyhydroxy compound and 70-120 parts by weight of fruit powder.
In the present invention, the pharmaceutical composition may further comprise other auxiliary ingredients according to formulation requirements, including but not limited to at least one of flavoring agents, essence, coloring agents, etc. The flavoring agent may be flavoring ingredient known in industry, such as saccharin sodium, aspartame, stevia, etc. The essence is known in the industry, such as various fruit essences and the like. The colorant is a common colorant, and can be natural pigment or 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 granule comprises the following components in parts by weight:
100-200 parts of acetylcysteine;
70-120 parts of fruit powder;
1270-1415 parts of sucrose I;
1280-1415 parts of sucrose II.
The raw materials and the auxiliary materials in the invention have different shapes, such as blank particles, acetylcysteine and sucrose crystals which are respectively nearly spherical, needle-shaped and square, and have poor mixing uniformity.
The invention provides two preparation methods of granules, namely a scheme I and a scheme II.
In the first scheme, the preparation process of uniformly mixing acetylcysteine and blank particles and quantitatively adding sucrose is adopted. In the first scheme, sucrose I is sucrose powder obtained by crushing sucrose and then sieving the crushed sucrose with an 80-mesh sieve for pretreatment; sucrose II is sucrose crystal.
Taking acetylcysteine granules as an example, according to a scheme I, the preparation process comprises the following steps:
(1) Weighing raw materials and auxiliary materials according to the prescription composition, mixing fruit powder and sucrose powder, granulating, drying, screening and obtaining blank granules;
(2) Uniformly mixing blank particles and acetylcysteine by adopting a progressive addition method to obtain a component A;
(3) And adding the component A and the sucrose crystals into a packaging bag according to a prescription proportion to obtain the acetylcysteine granules.
Preferably, according to scheme one, the preparation process of the acetylcysteine granules comprises the following steps:
(1) Weighing raw materials and auxiliary materials according to the prescription composition, mixing sweet orange juice powder and sucrose powder, adding saccharin sodium and sunset Huang Shifa for granulating, drying, screening and finishing, and collecting granules with the particle size meeting the requirement, and obtaining blank granules;
(2) Uniformly mixing blank particles, acetylcysteine and fresh orange juice essence by a progressive addition method to obtain a component A;
(3) And adding the component A and the sucrose crystals into a packaging bag according to a prescription proportion to obtain the acetylcysteine granules.
Further preferably, the granules prepared in the first embodiment comprise the following components in parts by weight:
100-200 parts of acetylcysteine;
100-120 parts of sweet orange juice powder;
1270-1400 parts of sucrose powder;
1280-1400 parts of sucrose crystals;
0-7.1 parts of saccharin sodium;
0-0.5 parts of sunset yellow;
0-3 parts of fresh orange juice essence.
In the second scheme, a preparation process of uniformly mixing acetylcysteine, blank particles and sucrose crystals is adopted. In the second scheme, sucrose I is sucrose powder obtained by crushing sucrose and then sieving with an 80-mesh sieve for pretreatment; sucrose II is sucrose crystal, and the sucrose crystal is characterized in that the particle size is within the range of 200-850 mu m, and the ratio of the sucrose crystal is 80-100%.
Taking acetylcysteine granules as an example, according to a second scheme, the preparation process comprises the following steps:
(1) Weighing raw materials and auxiliary materials according to the prescription, mixing fruit powder and sucrose powder, granulating, drying, screening and obtaining blank granules;
(2) Mixing blank particles, acetylcysteine and sucrose crystals uniformly by adopting a progressive addition method, and subpackaging to obtain acetylcysteine particles.
Preferably, according to scheme II, the preparation process of the acetylcysteine granules comprises the following steps:
(1) Weighing raw materials and auxiliary materials according to the prescription, mixing sweet orange juice powder and sucrose powder, adding saccharin sodium and sunset Huang Shifa for granulating, drying, screening and finishing, and collecting granules with the particle size meeting the requirement, and obtaining blank granules;
(2) And 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 further preferably, the granules prepared in scheme two comprise the following ingredients in parts by weight:
100-200 parts of acetylcysteine;
70-100 parts of sweet orange juice powder;
1350-1415 parts of sucrose powder;
1345-1415 parts of sucrose crystals;
0-6.5 parts of saccharin sodium;
0-0.5 parts of sunset yellow;
0-3.4 parts of fresh orange juice essence.
It is found that the composition, the particle size and the preparation process are further controlled in a combined way, so that the content uniformity and the stability of the preparation are further improved.
Advantageous effects
1. In the technical scheme of the invention, as the active ingredient acetylcysteine is unstable to damp and heat, part of auxiliary materials are adopted to be singly granulated to obtain blank particles, and the dried blank particles are mixed with the acetylcysteine and other auxiliary materials, so that the stability of the active ingredient acetylcysteine is improved, and the effectiveness and safety of the medicine are ensured.
2. The blank particles have large particle size and ratio difference compared with acetylcysteine, and the mixing uniformity is difficult to control. The invention further improves the content uniformity of the preparation through 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 mass production.
Drawings
FIG. 1 is a flow chart of the preparation process of examples 1-7.
Fig. 2 is a flowchart of the preparation process of 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 the following examples, which are only for explaining the present invention and do not represent the scope of the present invention defined by the claims.
The reagents and raw materials used in the invention are all commercially available.
Particle size control: the double screening method in the second method is referred to by the general rule 0982 of four portions of the edition of Chinese pharmacopoeia 2020, and the proportion (%) of the particles or powder which can pass through a large-aperture sieve and cannot pass through a small-aperture sieve is calculated as the particle size control limit.
Content uniformity measurement: the method for measuring the acetylcysteine particles (content measurement) in the second part of the 2020 edition is described in Chinese pharmacopoeia according to the term "rule 0512". Taking 1 bag of the product, transferring the whole content into a 200ml measuring flask, adding a proper amount of sodium metabisulfite solution (1-2000), shaking to dissolve and dilute to scale, filtering, taking the subsequent filtrate as a sample solution, taking a proper amount of acetylcysteine reference substance, precisely weighing, and adding sodium metabisulfite solution (1-2000) to dissolve and dilute to prepare a solution containing about 0.5mg of the reference substance solution in each 1 ml. Octadecylsilane chemically bonded silica is used as a filler; 0.05mol/L dipotassium hydrogen phosphate solution (pH value is adjusted to 3.0 by phosphoric acid) -methanol (90:10) is taken as a mobile phase; the detection wavelength is 214nm; the sample volume was 20. Mu.l. The number of theoretical plates is not less than 2000 calculated as acetylcysteine peak. Precisely measuring the sample solution and the reference substance solution, respectively injecting into a liquid chromatograph, and recording the chromatograms. Calculated as the peak area of acetylcysteine according to the external standard method.
Referring to the four general rules 0941 (content uniformity inspection method) of the Chinese pharmacopoeia 2020 edition, if the product A+2.2S is less than or equal to L (L=15.0), the content uniformity of the sample is determined to be in accordance with the regulation.
Specific embodiments of the invention are as follows:
example 1
1. Prescription composition
2. Particle diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 80.15%;
particle size of blank particles: the particle ratio of 200-1000 μm is 60.29%.
3. Preparation process
(1) Sucrose I is sucrose powder, and sucrose II is sucrose crystal. Weighing raw materials and auxiliary materials according to the prescription, mixing the orange juice powder and the sucrose powder in a wet granulator, adding a wetting agent for granulating, drying the wet granules in a fluidized bed, and sieving to obtain blank granules.
(2) And uniformly mixing the blank particles and acetylcysteine by adopting a progressive addition method to obtain a component A, wherein the rotating speed is 10~15 rpm,2~15min per time.
(3) And adding the component A and the sucrose crystals into a packaging bag according to the prescription proportion to obtain the acetylcysteine granules.
Example 2
1. The recipe composition and preparation process were the same as in example 1.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 80.15%;
particle size of blank particles: 200 μm to 1000 μm.
Example 3
1. The recipe composition and preparation process were the same as in example 1.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 90.46%;
particle size of blank particles: the particle ratio of 200-1000 μm is 80.20%.
Example 4
1. The recipe composition and preparation process were the same as in example 1.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: 200-600 μm;
particle size of blank particles: the particle ratio of 200-1000 μm is 60.29%.
Example 5
1. The recipe composition and preparation process were the same as in example 1.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: 200-600 μm;
particle size of blank particles: 200 μm to 1000 μm.
Example 6
1. Prescription composition
2. Particle diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 90.46%;
particle size of blank particles: the particle ratio of 200-1000 μm is 80.11%.
3. Preparation process
(1) Sucrose I is sucrose powder, and sucrose II is sucrose crystal. Weighing raw materials and auxiliary materials according to the prescription, mixing sweet orange juice powder and sucrose powder in a wet granulator, adding a wetting agent into an aqueous solution containing saccharin sodium and sunset yellow for granulating, drying the wet granules in a fluidized bed, and sieving to obtain blank granules.
(2) And uniformly mixing the blank particles, acetylcysteine and fresh orange juice essence by adopting a progressive addition method to obtain a component A, wherein the rotating speed is 10~15 rpm,2~15min/time.
(3) And adding the component A and the sucrose crystals into a packaging bag according to the prescription proportion to obtain the acetylcysteine granules.
Example 7
1. Prescription composition
2. Particle diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 90.46%;
particle size of blank particles: the particle ratio of 200-1000 μm is 80.32%.
3. The preparation process is the same as that of example 6
The prescription compositions of examples 1 to 7 are shown in Table 1, and the particle size parameters of the raw materials and auxiliary materials are shown in Table 2.
Table 1 prescription compositions of examples 1 to 7
Table 2 particle size parameters of the raw materials and auxiliary materials of examples 1 to 7
The content uniformity test data for the samples of examples 1 to 7 are shown below:
the small knot: in examples 1-7, the preparation process (scheme one) of uniformly mixing acetylcysteine and blank particles and quantitatively adding sucrose crystals is adopted, and the influence of acetylcysteine and blank particles with different particle diameters on content uniformity is examined. The content uniformity A+2.2S of the sample is less than or equal to 15, and meets the requirements, which shows that the self-made sample has good mixing uniformity of the acetylcysteine and the blank particles by controlling the ratio of the acetylcysteine particle size within the range of 200-600 mu m to be more than or equal to 80%, the ratio of the blank particle size within the range of 200-1000 mu m to be more than or equal to 60%. 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 diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 90.23%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 80.42%;
sucrose crystal particle size: 200 μm to 850 μm.
3. Preparation process
(1) Sucrose I is sucrose powder, and sucrose II is sucrose crystal. Weighing raw materials and auxiliary materials according to the prescription, mixing the orange juice powder and the sucrose powder in a wet granulator, adding a wetting agent for granulating, drying the wet granules in a fluidized bed, and sieving to obtain blank granules.
(2) The blank particles, acetylcysteine and sucrose crystals are uniformly mixed by adopting an additive method, and the rotating speed is 10~15 rpm,2~15min per time.
(3) And subpackaging the granules to obtain acetylcysteine granules.
Example 9
1. The recipe composition and preparation process were the same as in example 8.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 90.23%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 80.42%;
sucrose crystal particle size: the particle ratio of 200-850 μm is 90.19%.
Example 10
1. The recipe composition and preparation process were the same as in example 8.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 90.23%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 80.42%;
sucrose crystal particle size: the particle ratio of 200-850 μm is 80.07%.
Example 11
1. The recipe composition and preparation process were the same as in example 8.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 80.15%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 60.38%;
sucrose crystal particle size: 200 μm to 850 μm.
Example 12
1. The recipe composition and preparation process were the same as in example 8.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: the particle ratio of 200-600 μm is 80.15%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 60.38%;
sucrose crystal particle size: the particle ratio of 200-850 μm is 80.07%.
Example 13
1. The recipe composition and preparation process were the same as in example 8.
2. Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: 200-600 μm;
particle size of blank particles: 200-1000 μm;
sucrose crystal particle size: 200 μm to 850 μm.
Example 14
The recipe composition and preparation process were the same as in example 8.
Particle diameter parameters of raw materials and auxiliary materials:
acetylcysteine particle size: 200-600 μm;
particle size of blank particles: 200-1000 μm;
sucrose crystal particle size: the particle ratio of 200-850 μm is 80.07%.
Example 15
1. The prescription composition is shown in the following table:
2. particle diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 90.23%;
particle size of blank particles: the particle ratio of 200-1000 mu m is 80.34%;
sucrose crystal particle size: the particle ratio of 200-850 μm is 80.07%.
3. Preparation process
(1) Sucrose I is sucrose powder, and sucrose II is sucrose crystal. Weighing raw materials and auxiliary materials according to the prescription, mixing sweet orange powder and sucrose powder in a wet granulator, adding a wetting agent into an aqueous solution containing saccharin sodium and sunset yellow for granulating, drying the wet granules in a fluidized bed, and sieving to obtain blank granules.
(2) Mixing blank granule, acetylcysteine, sucrose crystal and fresh orange juice essence by progressive method at 10~15 rpm,2~15min/time.
(3) And subpackaging the granules to obtain acetylcysteine granules.
Example 16
1. Prescription composition
2. Particle diameter parameter of raw and auxiliary materials
Acetylcysteine particle size: the particle ratio of 200-600 μm is 90.23%;
particle size of blank particles: the particle ratio of 200-1000 μm is 80.26%;
sucrose crystal particle size: the particle ratio of 200-850 μm is 80.07%.
3. The preparation process was the same as in example 15.
The prescription compositions of examples 8-16 are shown in Table 3, and the particle size parameters of the raw materials and auxiliary materials are shown in Table 4.
Table 3 prescription composition of examples 8 to 16
Table 4 particle size parameters of the raw materials and auxiliary materials of examples 8 to 16
The content uniformity test data for the samples of examples 8 to 16 are shown below:
the small knot: examples 8-16 adopt a preparation process (scheme II) of uniformly mixing acetylcysteine, blank particles and sucrose crystals, and examine the influence of acetylcysteine, blank particles and sucrose crystals with different particle sizes on content uniformity. The content uniformity A+2.2S of the sample is less than or equal to 15, and meets the requirements, and the self-made sample is good in mixing uniformity of the three components, and the prepared preparation meets the requirements and is good in repeatability by controlling the content uniformity of the acetylcysteine to be more than or equal to 80%, the blank particle to be more than or equal to 60%, and the sucrose crystal to be more than or equal to 80%, wherein the content uniformity of the acetylcysteine is more than or equal to 200 mu m to 600 mu m.
Comparative example 1
The recipe composition and preparation process were the same as in example 2. Compared with the example 2, the difference is only that the particle diameter parameters of the raw materials and the auxiliary materials are that the proportion of the particles with the particle diameters of the acetylcysteine of 200-600 μm is 70.49 percent.
Comparative example 2
The recipe composition and preparation process were the same as in example 4. Compared with the embodiment 4, the particle size parameters of the raw materials and the auxiliary materials are only different, and the particle ratio of the blank particles with the particle size of 200-1000 μm is 50.21%.
Comparative example 3
The recipe composition and preparation process were the same as in example 10. Compared with the example 10, the particle size parameters of the raw materials and the auxiliary materials are only different in that the particle ratio of the sucrose crystal particle size is 70.37% between 200 μm and 850 μm.
Table 5 prescription composition of comparative examples 1 to 3
Table 6 particle diameter parameters of raw materials and auxiliary materials of comparative examples 1 to 3
Comparative examples 1 to 3 the content uniformity test data of the samples are shown in the following table.
TABLE 7 uniformity of sample content for comparative examples 1 to 3
As is clear from comparative examples 1 and 2, the preparation process (scheme I) of uniformly mixing acetylcysteine and blank particles and quantitatively adding sucrose is adopted, and when the range of 200-600 μm of the acetylcysteine particle size is 70% or the range of 200-1000 μm of the blank particle size is 50%, the uniformity of the sample content is not qualified.
As can be seen from comparative example 3, the preparation process (scheme II) of uniformly mixing acetylcysteine, blank particles and sucrose crystals is adopted, and when the sucrose crystal granularity is in the range of 200-850 μm and the ratio is 70%, the uniformity of the sample content is not qualified.
From comparative analyses of examples 1 to 5 and comparative examples 1 to 2, examples 8 to 14 and comparative example 3, it is clear that:
in the scheme I, the range of 200-600 mu m of the granularity of the acetylcysteine is controlled to be more than or equal to 80%, and the range of 200-1000 mu m of the granularity of the blank particle is controlled to be more than or equal to 60%; in the second scheme, the control of the granularity of the acetylcysteine is that the granularity of the acetylcysteine is 200-600 mu m in a range of more than or equal to 80%, the granularity of the blank particles is 200-1000 mu m in a range of more than or equal to 60%, the granularity of the sucrose crystals is 200-850 mu m in a range of 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 limit, the problem of uneven content of the preparation exists, and the particle size of the material is a high risk factor for causing the uniformity of the content of the preparation to be unacceptable.
In order to further illustrate the beneficial effects of the present invention, the present invention provides the following test examples.
Test example 1
Stability study of homemade samples and commercial products (Hainan Zanbang Fu Ji Shi) of example 3 and example 10 of the present invention.
The self-made samples of example 3 and example 10 and the commercial products (Hainan Zanbang Fushi) were selected and subjected to comparative investigation under a stability condition (acceleration condition: temperature 40 ℃ + -2 ℃ and humidity 75% RH+ -5% RH) for 6 months, and were sampled at the initial (or 0 month), 1 month, 2 months, 3 months and 6 months, respectively, and were measured according to the "Chinese pharmacopoeia" 2020 edition two section "acetylcysteine granules [ related substances ] [ loss on drying ] [ acidity ].
TABLE 8 data on substance detection
The research results show that the self-made samples of the embodiment 3 and the embodiment 10 basically accord with the commercial products in terms of drying weight loss and acidity data during 6 months stability investigation of the self-made samples and the commercial products, and meet the quality requirements; the self-made sample is slowly increased compared with the commercial products. The self-made sample has good stability.
Claims (6)
1. The acetylcysteine pharmaceutical composition is characterized by comprising an effective amount of acetylcysteine and blank particles, wherein the acetylcysteine accounts for 100-200 parts by weight, the blank particles account for 1300-1600 parts by weight, the acetylcysteine with the particle size ranging from 200 mu m to 600 mu m accounts for 80% -100% in the acetylcysteine, and the blank particles with the particle size ranging from 200 mu m to 1000 mu m account for 60% -100% in the blank particles;
the blank particles comprise 1270-1415 parts of water-soluble polyhydroxy compound and 70-120 parts of fruit powder;
the water-soluble polyhydroxy compound is sucrose powder;
the pharmaceutical composition is free of stabilizers and glidants;
the preparation of the pharmaceutical composition comprises the following steps: preparing blank particles from sucrose powder and fruit powder, and mixing the dried blank particles with acetylcysteine.
2. The pharmaceutical composition of claim 1, wherein the fruit powder is selected from one or more of orange fruit juice powder, grapefruit fruit powder, lemon fruit powder, orange fruit powder, blueberry fruit powder, grape fruit powder, apple fruit powder, orange fruit powder.
3. The pharmaceutical composition of claim 1, wherein the blank particles are admixed with acetylcysteine using an additive process.
4. Acetylcysteine granulate further prepared from the pharmaceutical composition of any of claims 1-3.
5. The acetylcysteine granules are characterized by comprising the following components in parts by weight:
100-200 parts of acetylcysteine;
70-120 parts of fruit powder;
1270-1415 parts of sucrose powder;
1280-1415 parts of sucrose crystals;
the acetylcysteine particles do not contain a stabilizer and a glidant;
the preparation method of the acetylcysteine particles comprises the following steps:
1) Weighing raw materials and auxiliary materials according to the prescription, mixing fruit powder and sucrose powder, granulating, drying, screening and obtaining blank granules;
2) Uniformly mixing the blank particles obtained in the step 1) and acetylcysteine by adopting a progressive addition method to obtain a component A, wherein the acetylcysteine with the particle size ranging from 200 mu m to 600 mu m accounts for 80% -100% of the acetylcysteine, and the blank particles with the particle size ranging from 200 mu m to 1000 mu m accounts for 60% -100% of the acetylcysteine;
3) And adding the component A and the sucrose crystals into a medicine packaging bag according to a prescription proportion to obtain the acetylcysteine granules.
6. The acetylcysteine granules are characterized by comprising the following components in parts by weight:
100-200 parts of acetylcysteine;
70-120 parts of fruit powder;
1270-1415 parts of sucrose powder;
1280-1415 parts of sucrose crystals;
the acetylcysteine particles do not contain a stabilizer and a glidant;
the preparation method of the acetylcysteine particles comprises the following steps:
1) Weighing raw materials and auxiliary materials according to the prescription, mixing fruit powder and sucrose powder, granulating, drying, screening and obtaining blank granules;
2) Uniformly mixing the blank particles, the acetylcysteine and the sucrose crystals obtained in the step 1) by adopting a progressive addition method to obtain the acetylcysteine particles, wherein the acetylcysteine with the particle size ranging from 200 mu m to 600 mu m accounts for 80% -100%, the blank particles with the particle size ranging from 200 mu m to 1000 mu m accounts for 60% -100%, and the sucrose crystals with the particle size ranging from 200 mu m to 850 mu m accounts for 80% -100%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211443283.8A CN115634205B (en) | 2022-11-18 | 2022-11-18 | Acetylcysteine particles and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211443283.8A CN115634205B (en) | 2022-11-18 | 2022-11-18 | Acetylcysteine particles and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115634205A CN115634205A (en) | 2023-01-24 |
| CN115634205B true CN115634205B (en) | 2023-05-30 |
Family
ID=84948478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211443283.8A Active CN115634205B (en) | 2022-11-18 | 2022-11-18 | Acetylcysteine particles and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115634205B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102743369A (en) * | 2012-06-19 | 2012-10-24 | 苏州朗易生物医药研究有限公司 | N-acetylcysteine pharmaceutical composition and preparation method thereof |
| CN103142505B (en) * | 2013-03-29 | 2015-03-11 | 山东罗欣药业集团股份有限公司 | Acetylcysteine composition granules and preparation method thereof |
| ITMI20132087A1 (en) * | 2013-12-13 | 2015-06-14 | Angelis Ettore De | DIETARY SUPPLEMENT |
| CN114886860B (en) * | 2022-06-28 | 2023-04-25 | 山东达因海洋生物制药股份有限公司 | Acetylcysteine pharmaceutical composition, preparation and preparation process thereof |
-
2022
- 2022-11-18 CN CN202211443283.8A patent/CN115634205B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN115634205A (en) | 2023-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK155194A3 (en) | Gastro-protected stable omeprazole composition in the form of microgranules and process for their production | |
| DE60026295T2 (en) | PLANT MATERIAL-CONTAINING GRANULATE AND METHOD OF MANUFACTURING | |
| DE60310982T2 (en) | USE OF BRANCHED MALTODEXTRIN AS GRANULAR BINDING AGENT | |
| CN112121027B (en) | Medicinal composition of oseltamivir phosphate coated granules, application and preparation method | |
| CN115837012A (en) | Amlodipine dry suspension and preparation method thereof | |
| CN109432044A (en) | A kind of preparation method of L-084 granula subtilis | |
| CN115634205B (en) | Acetylcysteine particles and preparation method thereof | |
| CN108186579A (en) | Xiao ' er Anfen Huangnamin composition grain and preparation method thereof | |
| CN112791054B (en) | Dry granulation method of dry suspension | |
| CN104997744B (en) | A kind of high stability capecitabine tablet and preparation method thereof | |
| JPH03173823A (en) | Vitamin b12s-containing composition | |
| EP0870537B1 (en) | Process for preparing alcohol-containing granules | |
| CN106860404A (en) | A kind of sildenafil citrate taste masking resin complexes and its application | |
| CN113750049B (en) | Soluble powder of antibacterial composition and preparation method thereof | |
| CN112546000A (en) | Clindamycin palmitate hydrochloride dry suspension and preparation method thereof | |
| CN114425037B (en) | Compound hydroxychlorozamine suspension and preparation method thereof | |
| CN104224725A (en) | Tebipenem pivoxil granule and preparation method thereof | |
| DE3012136C2 (en) | Process for the production of a granulate | |
| CN113181133A (en) | Preparation method of roxithromycin capsules | |
| CN106860408A (en) | A kind of glimepiride tablet | |
| CN117281780B (en) | Airotopaolamine dry suspension and preparation method thereof | |
| CN109432015B (en) | Everolimus particles and preparation method thereof | |
| CN115337271B (en) | Sodium picosulfate granule preparation and preparation process thereof | |
| CN107929250A (en) | A kind of revaprzan tablet composition | |
| JP4945917B2 (en) | Core particles for drug-containing coatings |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |