Acetylcysteine effervescent tablet and preparation process thereof

Abstract

The invention discloses an acetylcysteine effervescent tablet and a preparation process thereof, relating to the technical field of effervescent tablets. The raw material components thereof comprise, 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 a fragrance, 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 filler is any one or more of beta-cyclodextrin, maltodextrin, and lactose; the lubricant is any two of magnesium stearate, sodium lauryl sulfate, and lauryltrimethylammonium bromide; the sweetener is any one of sucralose and aspartame; the flavoring is any one of fresh orange essence, orange essence, and lemon essence; and the composite functional additive is any one or two of grafted modified starch and gray 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 form of medicine commonly used for 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 rate is slow, and the disintegration process of the drug solution in water is easily subject to environmental pollution, which may lead to 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 requires the use of more adhesives and stabilizers to ensure the structural integrity and disintegration performance of the effervescent tablets, which not only increases production costs, but also may affect the patient's taking experience.

[0003] During the tableting process, acetylcysteine effervescent tablets often experience sticking, resulting in low production efficiency and increased process complexity. In order to improve the disintegration rate and drug release effect of acetylcysteine effervescent tablets, traditional methods often rely on modified formulas or the introduction of additional additives. However, these methods may not effectively solve the contamination problem of the drug solution during the disintegration process, nor do they significantly reduce the production difficulty. 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 remains 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:

[0006] An acetylcysteine effervescent tablet, comprising the following raw materials by weight: 15-35 parts of acetylcysteine, 15-55 parts of an alkaline 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;

[0007] Furthermore, the alkali source is any one or two of sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate;

[0008] Furthermore, the filler is any one or more of β-cyclodextrin, maltodextrin, and lactose;

[0009] Furthermore, the lubricant is any two of magnesium stearate, sodium lauryl sulfate, and dodecyltrimethylammonium bromide;

[0010] Furthermore, the sweetener is any one of sucralose and aspartame;

[0011] Furthermore, the flavoring agent is any one of fresh orange flavor, tangerine flavor, and lemon flavor;

[0012] Furthermore, the composite functional auxiliary agent is any one or two of grafted modified starch and gray basil seed extract.

[0013] Furthermore, the preparation method of the grafted modified starch comprises the following steps:

[0014] 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 the unreacted substances and the product were separated by cellulose membrane dialysis tubing to obtain an amino-protected product;

[0015] The amino-protected product is added to dimethyl sulfoxide, and N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinimide, and dimethylaminopyridine are added, stirred evenly, and filtered. Starch is added to the filtered solution, stirred and reacted for 12-24 hours, and a mixed solution of trifluoroacetic acid and dichloromethane is added. The product is dried and deprotected, and the product is washed with deionized water and vacuum dried to obtain a grafted modified starch.

[0016] 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.

[0017] Furthermore, during the preparation of the grafted modified starch, the mass ratio of the amino protection product: N,N'-dicyclohexylcarbodiimide: N-hydroxysuccinimide: dimethylaminopyridine: starch was 0.5:0.28:0.15:0.01:0.22; and in the trifluoroacetic acid and dichloromethane mixed solution, the volume ratio of trifluoroacetic acid: dichloromethane was 1.9:26.6.

[0018] Furthermore, the preparation method of the gray basil seed extract comprises the following steps:

[0019] Add the seeds of the basil to deionized water preheated to a specified temperature and shake at a constant speed for 45-50 minutes. Add the swollen seeds to a wall-breaking machine and break them for 15-20 seconds. Filter using a vacuum pump and collect the colloidal mucus after wall-breaking. Centrifuge the colloidal mucus and precipitate it in a 95% ethanol solution. Place it in a 2-5°C environment and let it stand for 18-20 hours. Collect the precipitated mucus and place it at room temperature for 2-3 hours to evaporate the ethanol. Then, place it in a 60-65°C environment and dry it for 4-5 hours. Grind the dried mucus and sieve it to obtain the basil seed extract.

[0020] Furthermore, the uniform shaking rate is 100 rpm;

[0021] Furthermore, during the preparation of the 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 basil seeds.

[0022] Furthermore, 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);

[0023] 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).

[0024] 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).

[0025] A method for preparing acetylcysteine effervescent tablets 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;

[0026] S2: Loss on drying: Place the filler in a fluidized bed dryer and lose 4-5% on drying.

[0027] S3: Powder mixing and tableting: According to the ratio of raw material components, add acetylcysteine, sweetener, fragrance, alkaline 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 the tablet press to obtain acetylcysteine effervescent tablets.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. The purpose is to increase the disintegration rate, reduce the chance of environmental contamination of the drug solution during the disintegration of effervescent tablets in water, shorten the time patients have to wait for the drug to disintegrate during treatment, and improve the patient's medication experience during treatment. At the same time, without the introduction of additional adhesives, the use of lubricant compounding and the introduction of composite functional additives can reduce the sticking phenomenon during tableting, avoid contact with water through direct tableting, reduce the difficulty of process production, and improve production efficiency.

[0030] 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 properties of magnesium stearate are utilized to ensure that sticking is avoided during the tableting process. On the other hand, the surfactant having hydrophilic and hydrophobic groups is an amphiphilic molecule. The hydrophobic portion of the surfactant is combined with the carbon chain of magnesium stearate, exposing the hydrophilic group of the surfactant, converting the surface property 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.

[0031] 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 serve as a disintegration function aid to 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 medicines, an adhesive and a stabilizer in food, the present invention systematically extracts polymers from gray basil seeds, utilizes its polymer adhesive and the property of swelling and disintegrating when exposed to water, and uses it as a disintegration aid and an adhesive aid, and introduces it into the tablet preparation process together with the grafted modified starch. The prepared acetylcysteine effervescent tablets simultaneously meet the requirements of disintegration rate, dissolution rate, and avoidance of sticking and stagnant punching in large-scale production processes. DETAILED DESCRIPTION

[0032] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0033] In the following examples, the gray basil seeds were Thai basil seeds purchased from SAO Agricultural; the starch was natural tapioca starch; and the other raw materials were commercially available.

[0034] The preparation method of grafted modified starch comprises the following steps:

[0035] 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 and stirred for reaction for 24 h under ice bath conditions. The unreacted substances and the product were separated by cellulose membrane dialysis tubing to obtain the amino-protected product;

[0036] 0.5 g of the amino-protected product was added to dimethyl sulfoxide, and 0.28 g of N,N'-dicyclohexylcarbodiimide, 0.15 g of N-hydroxysuccinimide, and 0.01 g of dimethylaminopyridine were added, stirred evenly, and filtered. 0.2 gg of starch was added to the filtered solution, stirred and reacted for 12 h, 28.5 mL of a mixed solution of trifluoroacetic acid and dichloromethane was added, dried and deprotected, the product was washed with deionized water, and vacuum dried to obtain grafted modified starch.

[0037] The preparation method of the gray basil seed extract comprises the following steps:

[0038] 1 g of Ocimum basilicum seeds was added to 34.5 mL of deionized water preheated to 54°C and shaken at a constant speed for 45 minutes. The swollen seeds were added to a wall-breaking machine for 15 seconds and filtered using a vacuum pump. The colloidal mucus after wall-breaking was collected and centrifuged. The colloidal mucus was precipitated in 95% ethanol and allowed to stand at 2°C for 18 hours. The precipitated mucus was collected and placed at room temperature for 2 hours to evaporate the ethanol. It was then dried at 60°C for 4 hours. The dried mucus was ground and sieved to obtain the Ocimum basilicum seed extract.

[0039] Example 1: A method for preparing acetylcysteine effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium lauryl sulfate, and grafted modified starch through a 100-mesh sieve;

[0040] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0041] S3: Powder mixing and tableting: According to the ratio 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 a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium lauryl 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.

[0042] 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 essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, lauryltrimethylammonium bromide, and basil seed extract through a 100-mesh sieve;

[0043] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0044] S3: Powder mixing and tableting: According to the ratio 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 put into a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0045] 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 orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium lauryl sulfate, grafted modified starch, and basil seed extract through a 100-mesh sieve;

[0046] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0047] S3: Powder mixing and tableting: According to the ratio of raw material components, 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 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 lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is put into a tablet press to obtain acetylcysteine effervescent tablets.

[0048] Example 4: A method for preparing acetylcysteine effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: acetylcysteine, sucralose, and orange essence are sieved through a 24-mesh sieve, sodium bicarbonate is sieved through an 80-mesh sieve, and magnesium stearate, sodium lauryl sulfate, grafted modified starch, and basil seed extract are sieved through a 100-mesh sieve;

[0049] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0050] S3: Powder mixing and tableting: According to the ratio 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 lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0051] Example 5: A method for preparing acetylcysteine effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium lauryl sulfate, grafted modified starch, and basil seed extract through a 100-mesh sieve;

[0052] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0053] S3: Powder mixing and tableting: According to the ratio 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 lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0054] Example 6: A method for preparing acetylcysteine effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium lauryl sulfate, grafted modified starch, and basil seed extract through a 100-mesh sieve;

[0055] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0056] S3: Powder mixing and tableting: According to the ratio 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 lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0057] Example 7: A method for preparing acetylcysteine effervescent tablets, comprising the following steps: S1: pretreatment of raw materials and auxiliary materials: passing acetylcysteine, sucralose, and orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing magnesium stearate, sodium lauryl sulfate, grafted modified starch, and basil seed extract through a 100-mesh sieve;

[0058] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0059] S3: Powder mixing and tableting: According to the ratio 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 lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0060] Comparative Example 1: 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, grafted modified starch, and basil seed extract through a 100-mesh sieve;

[0061] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0062] S3: Powder mixing and tableting: According to the ratio 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 a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate are added and stirred for 10 minutes. After mixing evenly, the mixture is sent to a tablet press for tableting to obtain acetylcysteine effervescent tablets.

[0063] 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 orange essence through a 24-mesh sieve, passing sodium bicarbonate through an 80-mesh sieve, and passing sodium alginate, sodium lauryl sulfate, and grafted modified starch through a 100-mesh sieve;

[0064] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0065] S3: Powder mixing and tableting: According to the ratio 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 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.

[0066] 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 lauryl sulfate, and natural cassava starch through a 100-mesh sieve;

[0067] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0068] S3: Powder mixing and tableting: According to the ratio 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 tapioca starch, and 10 parts of β-cyclodextrin are added to a mixing device, mixed and stirred for 10 minutes, and then 1.5 parts of magnesium stearate and 0.5 parts of sodium lauryl sulfate are added and stirred for 10 minutes. After mixing evenly, the mixture is put into a tablet press to obtain acetylcysteine effervescent tablets.

[0069] 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 lauryl sulfate, and grafted modified starch through a 100-mesh sieve;

[0070] S2: Loss on drying: β-cyclodextrin was placed in a fluidized bed dryer and the loss on drying was 4%;

[0071] S3: Powder mixing and tableting: According to the raw material component ratio, 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 and mixed and stirred for 10 minutes. Then, 1.5 parts of magnesium stearate and 0.5 parts of cetyltrimethylammonium bromide are added and stirred for 10 minutes. After mixing evenly, the mixture is put into the tablet press to obtain acetylcysteine effervescent tablets.

[0072] 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;

[0073] The specific results are shown in Table 1 below;

[0074] Disintegration test: The disintegration time of the effervescent tablets prepared in the above examples and comparative examples was measured using a disintegration tester in deionized water at 37±2°C;

[0075] Dissolution test: The dissolution index of the effervescent tablets prepared in the above examples and comparative examples was measured using a dissolution apparatus in 900 mL of 0.1 N HCl at 37 ± 0.5 °C and a stirring speed of 100 rpm;

[0076] The specific results are shown in Table 2 below.

[0077] Table 1 Inspection table of sticking situation

[0078]

[0079] Table 2 Disintegration-dissolution test data

[0080]

[0081] Conclusion: The acetylcysteine effervescent tablets prepared in the present invention have excellent anti-sticking, high disintegration and high dissolution properties.

[0082] 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;

[0083] In Comparative Example 2, sodium alginate was used instead of magnesium stearate. The addition of surfactant to the hydrophilic excipient sodium alginate resulted in reduced wettability, increased disintegration time, and decreased dissolution index.

[0084] Comparative Example 3 used only ordinary tapioca starch, which resulted in an increase in disintegration time and a decrease in dissolution index.

[0085] In Comparative Example 4, long-chain hexadecyltrimethylammonium bromide was used instead of sodium lauryl sulfate. The short hydrophobic chain surfactant had a stronger effect on the tablet disintegration rate than the long hydrophobic chain surfactant, resulting in an increase in the disintegration time.

[0086] 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 invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations that come within the meaning and range of equivalents of the claims be embraced therein.

Claims

1. An acetylcysteine effervescent tablet, characterized in that: The raw material components thereof include, by weight, 15-35 parts of acetylcysteine, 15-55 parts of alkaline 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 alkaline source is sodium bicarbonate; The filler is β-cyclodextrin; The lubricant is composed of magnesium stearate and sodium lauryl sulfate or magnesium stearate and dodecyltrimethylammonium bromide; The sweetener is sucralose; The fragrance is fresh orange essence; The composite functional additive is any one or two of grafted modified starch and gray basil seed extract; 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 dialyzed to obtain the amino-protected product. The amino-protected product was added to dimethyl sulfoxide, and N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinimide, and dimethylaminopyridine were added, stirred evenly, and filtered. Starch was added to the filtered solution, stirred and reacted for 12-24 hours, and a mixed solution of trifluoroacetic acid and dichloromethane was added. The product was dried for deprotection, washed, and vacuum dried to obtain grafted modified starch. The preparation method of the gray basil seed extract comprises the following steps: The gray basil seeds are added to deionized water preheated to a specified temperature and shaken for 45-50 minutes. The swollen gray basil seeds are broken for 15-20 seconds, filtered, and the colloidal mucus after the broken wall is collected. The colloidal mucus is centrifuged and precipitated in a 95% ethanol solution and placed in an environment of 2-5°C for 18-20 hours. The precipitated mucus is collected and placed at room temperature for 2-3 hours to evaporate the ethanol, and then placed in an environment of 60-65°C for 4-5 hours. The dried mucus is ground and sieved to obtain the gray basil seed extract.

2. A kind of acetylcysteine effervescent tablet according to claim 1, it is characterized in that: During the preparation 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.

3. A kind of acetylcysteine effervescent tablet according to claim 1, it is characterized in that: During the preparation of the grafted modified starch, the mass ratio of the amino protection product: N,N'-dicyclohexylcarbodiimide: N-hydroxysuccinimide: dimethylaminopyridine: starch is 0.5:0.28:0.15:0.01:0.22; and in the trifluoroacetic acid and dichloromethane mixed solution, the volume ratio of trifluoroacetic acid: dichloromethane is 1.9:26.

6.

4. An acetylcysteine effervescent tablet according to claim 1, characterized in that: During the preparation of the 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 basil seeds.

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

6. 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 the grafted modified starch to the gray basil seed extract is (2-3):(1-2).

7. according to the preparation method of a kind of acetylcysteine effervescent tablet described in any one of claim 1-6, it is 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 source through an 80-90 mesh sieve, and pass lubricant 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 ratio of raw material components, add acetylcysteine, sweetener, fragrance, alkaline 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 the tablet press to obtain acetylcysteine effervescent tablets.

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