Carbocisteine tablet and preparation method thereof
Through fluidized bed granulation and hydroxypropyl methylcellulose coating technology, the problems of low compressibility and dissolution of carboxymestetan tablets were solved, and carboxymestetan tablets with high hardness, fast dissolution and stability were obtained. The agent improves the efficacy and stability.
Patent Information
- Application Number
- CN202310799753.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-03
- Publication Date
- 2025-01-03
AI Technical Summary
When the existing carboxymestetan tablets improve the compressibility of the material, they affect the release and absorption of drugs, and the dissolution of insoluble drugs is low, affecting the efficacy of drugs, and are prone to oxidation and have poor odor and poor stability.
The carboxystamp granule core is prepared by fluidized bed granulation technology, and coated with hydroxypropylmethylcellulose aqueous dispersion, combining surfactant and lubricant to improve the hardness and dissolution speed of the tablet.
Carboxymestetan tablets with high hardness, fast dissolution and good stability are achieved to meet transportation and drug efficacy needs.
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a tablet containing carbocysteine and a preparation method thereof. Background Art
[0002] Carbocisteine is a compound used to treat viscous sputum, difficulty in expectoration, and sputum blocking the trachea caused by diseases such as chronic bronchitis and bronchial asthma, with a molecular weight of 179.19. Currently, the main carbocisteine drugs on the market are carbocisteine tablets: 250mg, carbocisteine granules: 0.2g; 0.5g, and carbocisteine oral solution: 10ml: 0.2g; 10ml: 0.5g. Among them, carbocisteine accounts for about 90% of carbocisteine tablets, and other excipients account for a small proportion, so the compressibility of the material directly affects the hardness and brittleness of the finished tablets. At the same time, carbocisteine is poorly soluble in water, with a solubility of only 1.6mg / mL in water. It is a poorly soluble drug, so dissolution is a key factor affecting drug absorption. Most commercially available tablets use starch slurry as a binder and adopt a wet granulation process. Although high-viscosity starch slurry can significantly improve the compressibility of the material, it will affect the release and dissolution of the drug, delay the absorption of the drug in the body, and thus affect the efficacy. Therefore, it is necessary to improve the dissolution while improving the compressibility of the material. In addition, due to the carboxyl group in the molecular structure, carbocisteine has a sour smell and is easily oxidized. Coating technology is used to improve the smell and stability of the drug. Summary of the invention
[0003] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a carbocysteine tablet with higher hardness, faster dissolution, safety and stability through a large number of experimental studies, using carbocysteine as an active ingredient, polyvinyl alcohol aqueous solution as a wetting agent, and adopting fluidized bed granulation technology to prepare a particle core, which is compressed into a plain tablet and then coated with a hydroxypropyl methylcellulose aqueous dispersion, while improving the compressibility of the material.
[0004] Compared with the prior art, the carbocysteine tablets of the present invention have the following advantages and significant improvements: (1) high hardness, which meets the coating and transportation conditions; (2) fast dissolution; and (3) good stability.
[0005] The present invention is achieved through the following technical solutions: A carbocysteine tablet comprises the following steps: mixing carbocysteine and a disintegrant evenly in a fluidized bed, spraying a polyvinyl alcohol aqueous solution at a uniform speed to obtain carbocysteine particles; adding a surfactant and a lubricant after converting the yield, mixing evenly, and tableting to obtain carbocysteine tablets; and finally coating the carbocysteine tablets with a hydroxypropyl methylcellulose aqueous dispersion as a coating liquid to obtain the carbocysteine tablets.
[0006] Carbocisteine tablets include 85-95% carbocisteine by mass, 1-3% disintegrant by mass, 2-5% surfactant by mass, 1-2% lubricant by mass, and 2-3% hydroxypropyl methylcellulose aqueous dispersion by mass.
[0007] The present invention provides a method for preparing carbocysteine tablets, comprising the following steps: Preparation of carbocysteine granule core: after carbocysteine and disintegrant are mixed evenly, polyvinyl alcohol aqueous solution is used as a wetting agent to perform fluidized bed granulation to obtain carbocysteine granule core; (2) Preparation of carbocysteine tablets: after the carbocysteine granule core is converted into a yield, a surfactant and a lubricant are added, mixed evenly, and then tableted to obtain carbocysteine tablets; (3) Preparation of hydroxypropyl methylcellulose aqueous dispersion: after adding a certain amount of boiling water to a high shear stress stirring container, the stirring function is turned on and hydroxypropyl methylcellulose is added. After all particles are wetted, cold water is added and stirring is continued until they are completely dissolved; (4) Preparation of carbocysteine tablets: using the hydroxypropyl methylcellulose aqueous dispersion solution as a coating liquid, the plain tablets are coated. Implementation
[0008] The carbocysteine tablets obtained by the present invention have the characteristics of high hardness, fast dissolution and good stability. The following embodiments illustrate the present invention, but do not limit the present invention in any way.
[0009] Embodiment 1:
[0010] Preparation method: (1) Preparation of carbocisteine granule core: The fluidized bed was set at 40 °C and air volume of 10 m 3 / h, after mixing carboxycysteine and cross-linked sodium carboxymethyl cellulose evenly, spray 2% polyvinyl alcohol aqueous solution at a spray rate of 5 mL / min, and dry the water content to below 3% to obtain carboxycysteine granule core; (2) preparing carbocysteine tablets: adding sucrose fatty acid ester and magnesium stearate to the carbocysteine granules after calculating the yield, mixing evenly and pressing into tablets to obtain carbocysteine tablets; (3) Preparation of a hydroxypropyl methylcellulose aqueous dispersion: After adding a certain amount of boiling water to a high shear stress stirring container, start the stirring function and add hydroxypropyl methylcellulose, add cold water and continue stirring after all particles become wet, until they are completely dissolved; (4) Preparation of carbocysteine tablets: Set the coating pan speed to 5 r / min, the spray gun flow rate to 10 mL / min, the atomization pressure to 0.15 MPa, and the drying temperature to 40°C. Use hydroxypropyl methylcellulose aqueous dispersion as the coating liquid to coat carbocysteine tablets. After the weight gain reaches 3%, dry the tablets to obtain carbocysteine tablets. Example 2
[0011]
[0012] The preparation method is the same as Example 1. Example 3
[0013]
[0014] The preparation method is the same as Example 1.
[0015] Comparative Example 1:
[0016] Preparation method: Preparation of carbocysteine granules: Place the prescribed amount of carbocysteine and cross-linked sodium carboxymethyl cellulose in a wet granulator, set the stirring speed to 1500 rpm and the shear speed to 220 rpm, mix for 5 min, slowly add 2% polyvinyl alcohol aqueous solution with the same parameters as above for wet granulation, dry the water content to less than 3% to obtain carbocysteine granules, and the remaining steps are the same as Example 1.
[0017] Comparative Example 2:
[0018] The preparation method is the same as Example 1 except that there is no coating step.
[0019] The friability of each example and comparative example was determined with reference to the tablet friability test method (General Rule 0923) of the 2020 edition of the "Chinese Pharmacopoeia": Take a number of tablets so that their total weight is about 6.5g. Use a hair dryer to blow off the powder that falls off the tablets, weigh them accurately, place them in a cylinder, and rotate them 100 times. Take them out, remove the powder in the same way, weigh them accurately, the weight loss shall not exceed 1%, and no broken, cracked or crushed tablets shall be detected. This test is generally performed only once. If the weight loss exceeds 1%, it should be repeated twice, and the average weight loss of 3 times shall not exceed 1%, and no broken, cracked or crushed tablets shall be detected. The results are shown in Table 1
[0020] Referring to the dissolution and release test method of the 2020 edition of the Chinese Pharmacopoeia (General Rule 0931 Method 1), 1000 ml of phosphate buffered saline (pH 6.6) was used as the dissolution medium, the speed was set at 100 rpm / min, and the operation was carried out according to the law. After 30 minutes, samples were taken to determine the dissolution of carbocysteine. The results are shown in Table 2.
[0021]
[0022] The related substances of the samples of each embodiment and comparative embodiment at 0 day and 6 months stability are shown in Table 3.
[0023]
[0024] It can be seen from the above data that the carbocysteine tablets prepared in the embodiment of the present invention have high hardness, rapid dissolution and good stability.
Claims
1. A carbocysteine tablet, characterized in that The tablet is prepared by coating the granule core containing the main drug component after tablet compression.
2. The carbocysteine tablet according to claim 1, characterized in that The particle core is composed of carbocysteine, a disintegrant, a wetting agent, a surfactant and a lubricant, and the coating component is composed of a hydroxypropyl methylcellulose aqueous dispersion, wherein the mass fraction of carbocysteine is 85-95%, the mass fraction of the disintegrant is 1-3%, the mass fraction of the surfactant is 2-5%, the mass fraction of the lubricant is 1-2%, and the mass fraction of the hydroxypropyl methylcellulose aqueous dispersion is 2-3%.
3. The carbocysteine tablet according to claim 2, characterized in that The disintegrant is selected from one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, and cross-linked polyvinylpyrrolidone.
4. The carbocysteine tablet according to claim 2, characterized in that The surfactant is selected from one or more of glyceryl behenate and sucrose fatty acid ester.
5. The carbocysteine tablet according to claim 2, characterized in that The lubricant is selected from one or more of magnesium stearate and sodium stearate fumarate.
6. The carbocysteine tablet according to claim 2, characterized in that The preparation method comprises the following steps: (1) preparing carbocysteine granule cores: mixing carbocysteine and a disintegrant uniformly, and then granulating the mixture in a fluidized bed using a polyvinyl alcohol aqueous solution as a wetting agent to prepare carbocysteine granule cores; (2) preparing carbocysteine tablets: adding a surfactant and a lubricant to the carbocysteine granule core after calculating the yield, mixing them evenly and then tableting to obtain carbocysteine tablets; (3) Preparation of a hydroxypropyl methylcellulose aqueous dispersion: After adding a certain amount of boiling water to a high shear stress stirring container, start the stirring function and add hydroxypropyl methylcellulose, add cold water and continue stirring after all particles become wet, until they are completely dissolved; (4) Preparation of carbocysteine tablets: Use the aqueous dispersion solution of hydroxypropyl methylcellulose as the coating liquid to coat the plain tablets.
7. The method for preparing carbocysteine tablets according to claim 7, characterized in that: In step (1), the spray rate is 5-10 mL / min, the temperature is 40-50°C, and the air volume is 10-20 m 3 / h.
8. The method for preparing carbocysteine tablets according to claim 7, characterized in that: In step (4), the rotation speed of the coating pan is 5-10 r / min, the flow rate of the spray gun is 8-10 mL / min, the atomization pressure is 0.15 Mpa, and the drying temperature is 40-50°C.