Acetylcysteine effervescent tablet and preparation process thereof

Abstract

The invention discloses an acetylcysteine effervescent tablet and a preparation process thereof, and relates to the technical field of effervescent tablets, the acetylcysteine effervescent tablet comprises the following raw material components by mass: 15-35 parts of acetylcysteine, 15-55 parts of an alkali source, 5-25 parts of a filler, 1.5-3.5 parts of a lubricant, 0.5-1.5 parts of a sweetener, 1-5 parts of an aromatic, and 4-12 parts of a composite functional additive; the alkali source is any one or two of sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate; the filling agent is any one or more of beta-cyclodextrin, maltodextrin and lactose; the lubricant is any two of magnesium stearate, lauryl sodium sulfate and dodecyl trimethyl ammonium bromide; the sweetening agent is any one of sucralose and aspartame; the flavoring agent is any one of fresh orange essence, orange essence and lemon essence; the composite functional additive is any one or two of graft modified starch and basil seed extract.

Description

Technical Field

[0001] The invention relates to the technical field of effervescent tablets, in particular to an acetylcysteine ​​effervescent tablet and a preparation process thereof. Background Art

[0002] Acetylcysteine ​​effervescent tablets, as a drug form commonly used in respiratory diseases, have gradually attracted attention in recent years. However, in the preparation process of acetylcysteine ​​effervescent tablets, there are still some technical challenges. First, the traditional effervescent tablet disintegration speed is slow, and the disintegration process of the drug solution in water is easily polluted by the environment, which may lead to the instability of the drug effect and affect the therapeutic effect of the drug. At the same time, due to the chemical properties of acetylcysteine ​​itself, its reaction with water may cause the drug concentration in the solution to fluctuate, thereby affecting the release of drug effect. In addition, the existing production process usually needs to use more adhesives and stabilizers to ensure the structural integrity and disintegration performance of the effervescent tablets, which not only increases the production cost, but also may affect the patient's taking experience.

[0003] During the tableting process, acetylcysteine ​​effervescent tablets often have sticking phenomenon, resulting in low production efficiency and increasing process complexity. In order to improve the disintegration rate and drug release effect of acetylcysteine ​​effervescent tablets, traditional methods often rely on improved formulas or the introduction of additional additives. However, these methods may not be able to effectively solve the pollution problem of drug solutions during the disintegration process, and have not been able to significantly reduce the difficulty of production. Therefore, how to simplify the production process, improve the disintegration efficiency of acetylcysteine ​​effervescent tablets, and improve the patient's medication experience without adding additional adhesives is still a technical problem that the current pharmaceutical industry urgently needs to break through. Summary of the invention

[0004] The object of the present invention is to provide an acetylcysteine ​​effervescent tablet and a preparation process thereof, so as to solve the problems raised in the prior art.

[0005] To achieve the above object, the present invention provides the following technical solutions: An acetylcysteine ​​effervescent tablet, the raw material components of which include, by weight: 15-35 parts of acetylcysteine, 15-55 parts of an alkali source, 5-25 parts of a filler, 1.5-3.5 parts of a lubricant, 0.5-1.5 parts of a sweetener, 1-5 parts of a fragrance, and 4-12 parts of a composite functional additive; Further, the alkali source is any one or two of sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate; Furthermore, the filler is any one or more of β-cyclodextrin, maltodextrin, and lactose; Furthermore, the lubricant is any two of magnesium stearate, sodium lauryl sulfate, and dodecyltrimethylammonium bromide; Furthermore, the sweetener is any one of sucralose and aspartame; Furthermore, the flavoring agent is any one of fresh orange flavor, tangerine flavor, and lemon flavor; Furthermore, the composite functional auxiliary agent is any one or two of grafted modified starch and gray basil seed extract.

[0006] Furthermore, the preparation method of the grafted modified starch comprises the following steps: L-leucine, di-tert-butyl dicarbonate and sodium bicarbonate were added to a tetrahydrofuran aqueous solution, stirred and reacted for 24 hours under ice bath conditions, and unreacted substances and products were separated by cellulose membrane dialysis tubes to obtain amino-protected products; The amino-protected product is added to dimethyl sulfoxide, and N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinimide, and dimethylaminopyridine are added, stirred evenly, filtered, and starch is added to the filtered solution, stirred to react for 12-24 hours, and a trifluoroacetic acid and dichloromethane mixed solution is added, dried and deprotected, and the product is washed with deionized water and vacuum dried to obtain a grafted modified starch.

[0007] Furthermore, in the preparation process of the amino-protected product, the mass ratio of L-leucine: di-tert-butyl dicarbonate: sodium bicarbonate is 2.63:5.23:0.02; and in the tetrahydrofuran aqueous solution, the volume ratio of tetrahydrofuran: water is 1:1.

[0008] Furthermore, in the preparation process of the grafted modified starch, the mass ratio of amino protection product: N,N'-dicyclohexylcarbodiimide: N-hydroxysuccinimide: dimethylaminopyridine: starch is 0.5:0.28:0.15:0.01:0.22; in the trifluoroacetic acid and dichloromethane mixed solution, the volume ratio of trifluoroacetic acid: dichloromethane is 1.9:26.6.

[0009] Furthermore, the preparation method of the gray basil seed extract comprises the following steps: Add the gray basil seeds to deionized water preheated to a specified temperature, shake at a constant speed for 45-50 minutes, add the expanded gray basil seeds to a wall-breaking machine for 15-20 seconds, filter with a vacuum pump, collect the colloidal mucus after the wall-breaking, centrifuge the colloidal mucus, precipitate it in a 95% ethanol solution and place it in a 2-5°C environment for 18-20 hours, collect the precipitated mucus and place it at room temperature for 2-3 hours to evaporate the ethanol, and then place it in a 60-65°C environment to dry for 4-5 hours. Grind the dried mucus and sieve it to obtain the gray basil seed extract.

[0010] Furthermore, the uniform shaking rate is 100 rpm; Furthermore, during the preparation of the gray basil seed extract, the extract is preheated to a specified temperature of 50-57° C., and 30-35 mL of deionized water is added per 1 g of gray basil seeds.

[0011] Further, the lubricant is composed of magnesium stearate and sodium lauryl sulfate, wherein the mass ratio of magnesium stearate:sodium lauryl sulfate is 1.5:(0.5-2); Furthermore, the lubricant is composed of magnesium stearate and dodecyltrimethylammonium bromide, wherein the mass ratio of magnesium stearate to dodecyltrimethylammonium bromide is 1.5:(0.5-2).

[0012] Furthermore, the composite functional auxiliary agent is composed of grafted modified starch and gray basil seed extract, wherein the mass ratio of grafted modified starch to gray basil seed extract is (2-3):(1-2).

[0013] A method for preparing an acetylcysteine ​​effervescent tablet comprises the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sweeteners, and aromatics through a 24-30 mesh sieve, passing an alkali source through an 80-90 mesh sieve, and passing a lubricant and a composite functional additive through a 100-120 mesh sieve; S2: Loss on drying: Place the filler in a fluidized bed dryer and lose 4-5% on drying; S3: Powder mixing and tableting: according to the proportion of raw material components, add acetylcysteine, sweetener, fragrance, alkali source, composite functional additives and filler into the mixing equipment, mix and stir for 5-15 minutes, then add lubricant, continue stirring for 5-15 minutes, mix evenly and then press into tablet machine to obtain acetylcysteine ​​effervescent tablets.

[0014] Compared with the prior art, the present invention has the following beneficial effects: 1. The purpose is to increase the disintegration rate, reduce the probability of drug solution being polluted by the environment during the disintegration of effervescent tablets in water, shorten the time patients have to wait for drug disintegration during treatment, and improve patients' medication experience during treatment. At the same time, without the additional introduction of adhesives, the lubricant compound and the introduction of composite functional additives can be used to reduce the sticking phenomenon during tableting, avoid contact with water by direct tableting, reduce the difficulty of process production, and improve production efficiency.

[0015] 2. The presence of magnesium stearate, a traditional lubricant, increases the hydrophobicity of the powder, resulting in delayed drug dissolution. The present invention, while retaining magnesium stearate as a lubricant, simultaneously introduces a surfactant having a long-chain alkane. On the one hand, the hydrophobic property of magnesium stearate is utilized to ensure that sticking is avoided during tableting. On the other hand, the surfactant having hydrophilic and hydrophobic groups is an amphiphilic molecule. The hydrophobic part of the surfactant is combined with the carbon chain of magnesium stearate, so that the hydrophilic group of the surfactant is exposed, and the surface property is changed from hydrophobic to hydrophilic, thereby improving the wettability of magnesium stearate in the tablet and ensuring the disintegration of the tablet in water and the drug release rate.

[0016] 3. The present invention uses endogenous amino acids (L-leucine) as a synthetic basis to prepare L-leucine grafted starch. Modifying the hydrophilic amino acid leucine on the starch can improve its disintegration ability, and as a disintegration function aid, further improve the disintegration rate of the tablet and the drug dissolution rate; on this basis, inspired by basil seed gum, which is a thickener and suspending agent in medicine, an adhesive and a stabilizer in food, the present invention extracts polymers from gray basil seeds in a systematic manner, utilizes its polymer adhesive and the characteristics of swelling and disintegration when exposed to water, and uses it as a disintegration aid and an adhesive aid, and introduces it into the preparation process of the tablet together with the grafted modified starch, so that the prepared acetylcysteine ​​effervescent tablets simultaneously meet the requirements of disintegration rate, dissolution rate, and avoiding the sticking and stagnant phenomena in the large-scale production process. DETAILED DESCRIPTION

[0017] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0018] In the following examples, the gray basil seeds are Thai basil seeds purchased from SAO Agricultural; the starch is natural cassava starch; and the other raw materials are commercially available.

[0019] The preparation method of grafted modified starch comprises the following steps: 2.63 g of L-leucine, 5.23 g of di-tert-butyl dicarbonate, and 0.02 g of sodium bicarbonate were added to 50 mL of tetrahydrofuran aqueous solution, stirred for reaction for 24 h under ice bath conditions, and the unreacted substances and products were separated by cellulose membrane dialysis tube to obtain an amino-protected product; Add 0.5 g of the amino-protected product to dimethyl sulfoxide, add 0.28 g of N,N'-dicyclohexylcarbodiimide, 0.15 g of N-hydroxysuccinimide, and 0.01 g of dimethylaminopyridine, stir evenly, filter, add 0.2 gg of starch to the filtered solution, stir and react for 12 h, add 28.5 mL of a trifluoroacetic acid and dichloromethane mixed solution, dry and deprotect, wash the product with deionized water, and vacuum dry to obtain a grafted modified starch.

[0020] The preparation method of the gray basil seed extract comprises the following steps: 1 g of gray basil seeds was added to 34.5 mL of deionized water preheated to 54°C, and the mixture was shaken at a constant speed for 45 min. The expanded gray basil seeds were added to a wall-breaking machine for 15 s, and the mixture was filtered using a vacuum pump. The colloidal mucus after wall-breaking was collected, and the colloidal mucus was centrifuged and precipitated in a 95% ethanol solution and placed in a 2°C environment for 18 h. The precipitated mucus was collected and placed at room temperature for 2 h to evaporate the ethanol, and then placed in a 60°C environment for 4 h to dry. The dried mucus was ground and sieved to obtain the gray basil seed extract.

[0021] Example 1: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, and grafted modified starch through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of grafted modified starch, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0022] Example 2: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, dodecyltrimethylammonium bromide, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of gray basil seed extract, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of dodecyltrimethylammonium bromide are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0023] Example 3: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, add 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 3 parts of grafted modified starch, 1 part of gray basil seed extract, and 10 parts of β-cyclodextrin into a mixing device, mix and stir for 10 minutes, then add 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate, continue stirring for 10 minutes, mix evenly, and then put into a tablet press to obtain acetylcysteine ​​effervescent tablets.

[0024] Example 4: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 2 parts of grafted modified starch, 2 parts of gray basil seed extract, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0025] Example 5: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 6 parts of grafted modified starch, 2 parts of gray basil seed extract, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0026] Example 6: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 9 parts of grafted modified starch, 3 parts of gray basil seed extract, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0027] Example 7: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 9 parts of grafted modified starch, 3 parts of gray basil seed extract, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 2 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0028] Comparative Example 1: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, grafted modified starch, and gray basil seed extract through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of grafted modified starch, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0029] Comparative Example 2: A method for preparing acetylcysteine ​​effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing sodium alginate, sodium dodecyl sulfate, and grafted modified starch through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of grafted modified starch, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of sodium alginate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0030] Comparative Example 3: A method for preparing acetylcysteine ​​effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, and natural cassava starch through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of natural cassava starch, and 10 parts of β-cyclodextrin are added into a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium dodecyl sulfate are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine ​​effervescent tablets.

[0031] Comparative Example 4: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: A method for preparing an acetylcysteine ​​effervescent tablet, comprising the following steps: S1: Pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and fresh orange flavor through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium dodecyl sulfate, and grafted modified starch through a 100-mesh sieve; S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%; S3: Powder mixing and tableting: According to the proportion of raw material components, 35 parts of acetylcysteine, 0.5 parts of sucralose, 1 part of fresh orange essence, 30 parts of sodium bicarbonate, 4 parts of grafted modified starch, and 10 parts of β-cyclodextrin are added to the mixing equipment, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of hexadecyltrimethylammonium bromide are added, and stirring is continued for 10 minutes. After mixing evenly, the mixture is sent to the tablet press to obtain acetylcysteine ​​effervescent tablets. Experiment: Sticking and punching experiment: The sticking and punching conditions during tableting in Examples 1-7 of the present invention and Comparative Example 2 were investigated; The specific results are shown in Table 1 below; Disintegration test: The disintegration time of the effervescent tablets prepared in the above examples and comparative examples was measured in deionized water at 37±2°C using a disintegration tester; Dissolution test: The dissolution index of the effervescent tablets prepared in the above examples and comparative examples was measured using a dissolution instrument in 900 mL 0.1 N HCl at 37 ± 0.5 °C and a stirring speed of 100 rpm; The specific results are shown in Table 2 below.

[0032] Table 1 Inspection table of sticking situation

[0033] Table 2 Disintegration-dissolution test data

[0034] Conclusion: The acetylcysteine ​​effervescent tablets prepared by the present invention have excellent anti-sticking, high disintegration and high dissolution properties.

[0035] In Comparative Example 1, only magnesium stearate was used as a single lubricant, resulting in an increase in disintegration time and a decrease in dissolution index; In Comparative Example 2, sodium alginate was used to replace magnesium stearate. After the addition of surfactant, the hydrophilic excipient sodium alginate resulted in reduced wettability, increased disintegration time, and reduced dissolution index. In Comparative Example 3, only ordinary tapioca starch was used, resulting in an increase in disintegration time and a decrease in dissolution index.

[0036] In Comparative Example 4, long-chain hexadecyltrimethylammonium bromide was used to replace sodium dodecyl sulfate. The effect of the short hydrophobic chain surfactant on the tablet disintegration rate was stronger than that of the long hydrophobic chain surfactant, resulting in an increase in the disintegration time.

[0037] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

Claims

1. An acetylcysteine ​​effervescent tablet, characterized in that: The raw material components include, by weight: 15-35 parts of acetylcysteine, 15-55 parts of alkali source, 5-25 parts of filler, 1.5-3.5 parts of lubricant, 0.5-1.5 parts of sweetener, 1-5 parts of aromatic agent, and 4-12 parts of composite functional additives; The alkali source is any one or two of sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate; The filler is any one or more of β-cyclodextrin, maltodextrin, and lactose; The lubricant is any two of magnesium stearate, sodium lauryl sulfate, and dodecyltrimethylammonium bromide; The sweetener is any one of sucralose and aspartame; The flavoring agent is any one of fresh orange flavor, tangerine flavor, and lemon flavor; The composite functional auxiliary agent is any one or two of grafted modified starch and gray basil seed extract.

2. A kind of acetylcysteine ​​effervescent tablet according to claim 1, characterized in that: The preparation method of the grafted modified starch comprises the following steps: L-leucine, di-tert-butyl dicarbonate and sodium bicarbonate were added to a tetrahydrofuran aqueous solution, stirred for reaction for 24 hours under ice bath conditions, and dialyzed to obtain an amino-protected product; The amino-protected product is added to dimethyl sulfoxide, and N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinimide, and dimethylaminopyridine are added, stirred evenly, filtered, and starch is added to the filtered solution, stirred to react for 12-24 hours, and a trifluoroacetic acid and dichloromethane mixed solution is added, dried and deprotected, washed, and vacuum dried to obtain a grafted modified starch.

3. A kind of acetylcysteine ​​effervescent tablet according to claim 2, characterized in that: In the preparation process of the amino-protected product, the mass ratio of L-leucine: di-tert-butyl dicarbonate: sodium bicarbonate is 2.63:5.23:0.02; and in the tetrahydrofuran aqueous solution, the volume ratio of tetrahydrofuran: water is 1:

1.

4. A kind of acetylcysteine ​​effervescent tablet according to claim 2, characterized in that: In the preparation process of grafted modified starch, the mass ratio of amino protection product: N,N'-dicyclohexylcarbodiimide: N-hydroxysuccinimide: dimethylaminopyridine: starch is 0.5:0.28:0.15:0.01:0.22; in the trifluoroacetic acid and dichloromethane mixed solution, the volume ratio of trifluoroacetic acid: dichloromethane is 1.9:26.

6.

5. An acetylcysteine ​​effervescent tablet according to claim 1, characterized in that: The preparation method of the gray basil seed extract comprises the following steps: Add the gray basil seeds to deionized water preheated to a specified temperature, shake for 45-50 minutes, break the expanded gray basil seeds for 15-20 seconds, filter, collect the colloidal mucus after breaking the wall, centrifuge the colloidal mucus, precipitate it in a 95% ethanol solution and place it in a 2-5°C environment for 18-20 hours, collect the precipitated mucus and place it at room temperature for 2-3 hours to evaporate the ethanol, and then place it in a 60-65°C environment to dry for 4-5 hours. Grind the dried mucus and sieve it to obtain the gray basil seed extract.

6. An acetylcysteine ​​effervescent tablet according to claim 5, characterized in that: During the preparation of the gray basil seed extract, the extract is preheated to a specified temperature of 50-57° C., and 30-35 mL of deionized water is added per 1 g of gray basil seeds.

7. An acetylcysteine ​​effervescent tablet according to claim 1, characterized in that: The lubricant is composed of magnesium stearate and sodium lauryl sulfate, wherein the mass ratio of magnesium stearate to sodium lauryl sulfate is 1.5:(0.5-2); the lubricant is composed of magnesium stearate and dodecyltrimethylammonium bromide, wherein the mass ratio of magnesium stearate to dodecyltrimethylammonium bromide is 1.5:(0.5-2).

8. An acetylcysteine ​​effervescent tablet according to claim 1, characterized in that: The composite functional auxiliary agent is composed of grafted modified starch and gray basil seed extract, wherein the mass ratio of grafted modified starch to gray basil seed extract is (2-3):(1-2).

9. A method for preparing an acetylcysteine ​​effervescent tablet, characterized in that: The following steps are involved: S1: Pretreatment of raw materials and auxiliary materials: pass acetylcysteine, sweeteners, and fragrances through a 24-30 mesh sieve, pass alkali sources through a 80-90 mesh sieve, and pass lubricants and composite functional additives through a 100-120 mesh sieve; S2: Loss on drying: Place the filler in a fluidized bed dryer and lose 4-5% on drying; S3: Powder mixing and tableting: according to the proportion of raw material components, add acetylcysteine, sweetener, fragrance, alkali source, composite functional additives and filler into the mixing equipment, mix and stir for 5-15 minutes, then add lubricant, continue stirring for 5-15 minutes, mix evenly and then press into tablet machine to obtain acetylcysteine ​​effervescent tablets.

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