Method for preparing compound zinc cloth tablets

Abstract

The invention relates to a method for preparing a compound zinc cloth tablet, and belongs to the technical field of medicine production, and the method comprises the following steps: S1, crushing and screening zinc gluconate and chlorpheniramine maleate; s2, corn starch, dextrin and purified water are prepared into 7%-8% mixed paste as an adhesive; s3, the crushed and screened zinc gluconate, chlorpheniramine maleate, ibuprofen, the filler and the disintegrating agent are subjected to dry mixing, and after mixing is completed, an adhesive is added for wet granulation; and S4, after wet granulation, drying and finishing particles, adding a disintegrating agent, a lubricating agent and a flow aid, uniformly mixing, and tabletting to obtain the compound zinc cloth tablets. The product prepared by the method is good in quality stability and dissolution effect, and the process is common and suitable for commercial production.

Description

Technical Field

[0001] The invention belongs to the technical field of drug production, and particularly relates to a method for preparing a compound zinc cloth sheet. Background Art

[0002] Compound zinc cloth sheet is a compound preparation used to relieve cold symptoms, including three main ingredients: ibuprofen, zinc gluconate and chlorpheniramine maleate.

[0003] Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis by inhibiting cyclooxygenase (COX), thereby exerting antipyretic, analgesic and anti-inflammatory effects. However, its poor water solubility (needle-shaped crystals) and low solubility limit its bioavailability.

[0004] The zinc ions in zinc gluconate can inhibit viral replication, enhance immune cell activity, and shorten the course of colds. As a strong base and weak acid salt, it is highly water-soluble, but its effect on alleviating cold symptoms when used alone is limited.

[0005] Chlorpheniramine maleate is an antihistamine that relieves allergic symptoms such as nasal congestion and runny nose by blocking H1 receptors. It is moderately water-soluble but requires simultaneous release with other ingredients to achieve a synergistic effect.

[0006] The combined use of ibuprofen, zinc gluconate and chlorpheniramine maleate can comprehensively relieve symptoms such as fever, pain, and nasal congestion, but the problem of asynchronous release of different ingredients in the gastrointestinal tract needs to be solved to achieve the best synergistic effect. Summary of the Invention

[0007] Currently, granules dominate the market for compound preparations with ibuprofen, chlorpheniramine maleate, and zinc gluconate as core ingredients. The technical research and development of this dosage form focuses on three main areas: improving palatability through flavor correction technology, optimizing the formulation process to enhance stability, and constructing a multi-component synergistic release system. Compared to traditional tablets, granules offer significant advantages in achieving simultaneous dissolution of the three main components, and their dispersed delivery characteristics are more conducive to the simultaneous release of active ingredients with different solubilities. Furthermore, granules excel in patient compliance, and their modulatable fluid form meets the swallowing needs of both children and adults.

[0008] However, there are still several technical bottlenecks in compound zinc cloth granules that need to be overcome: first, the inherent hydrophobic properties of ibuprofen make it difficult to dissolve in aqueous media, and drug adsorption and loss are prone to occur during the oral administration process, which directly affects the bioavailability; second, the significant bitter taste of this ingredient exacerbates the resistance of patients (especially children) to taking the medicine; third, the current formulation contains too high a proportion of sucrose as the main filler (usually 50%-70%), which seriously limits the medication options for diabetic patients.

[0009] To address these shortcomings, tablet dosage form development offers unique advantages: its direct solid administration method avoids drug loss during the dissolution process, while novel excipient systems enable sugar-free formulations. However, the key technical challenge in tablet development lies in constructing a multi-component simultaneous release system—requiring innovative formulation processes to ensure balanced dissolution kinetics of the water-soluble zinc gluconate, the moderately soluble chlorpheniramine maleate, and the poorly soluble ibuprofen in the gastrointestinal tract.

[0010] The purpose of the present invention is to provide a method for preparing a compound zinc cloth sheet. The preparation method provided by the present invention is a conventional wet granulation process, which is simple and easy to implement. The prepared compound zinc cloth sheet has a fast disintegration speed, high release efficiency and stable product quality.

[0011] The present invention adopts the following technical solutions to achieve its purpose:

[0012] A method for preparing a composite zinc cloth sheet comprises the following steps:

[0013] The zinc gluconate and chlorpheniramine maleate raw materials were crushed and sieved through 80 mesh to increase the dissolution rate of the drugs in vivo, thereby improving the bioavailability of each component. The mass ratio of ibuprofen, zinc gluconate and chlorpheniramine maleate was 75:50:1.

[0014] Corn starch, dextrin and purified water are prepared into a 7%-8% mixed paste as a binder. Dextrin can make up for the lack of viscosity of starch as a binder. The disintegration property of starch can ensure the rapid release of the drug through secondary disintegration. The mass ratio of corn starch to dextrin is between 3:1 and 3:2.

[0015] The crushed and sieved zinc gluconate, chlorpheniramine maleate, ibuprofen, filler and disintegrant are dry-mixed, and a binder is added after mixing for wet granulation. During the wet granulation process, the binder fixes the different components inside the granules, solving the problem of stratification caused by large differences in density and particle size of the components in the compound preparation;

[0016] The particles are dried and granulated, and then evenly mixed with an external disintegrant, a lubricant and a glidant, and then tabletted to obtain a compound zinc cloth tablet. The internal and external disintegrants are added to ensure the disintegration rate of the tablet.

[0017] Preferably, the compound zinc cloth sheet comprises the following components in percentage by weight: 35% to 45% of raw materials, 45% to 55% of fillers, 2% to 5% of binders, 3% to 7% of disintegrants, 0.5% to 2% of lubricants, and 0.1% to 1.5% of glidants;

[0018] Preferably, the filler comprises lactose, and / or corn starch, and / or microcrystalline cellulose, and / or dextrin.

[0019] Preferably, the disintegrant comprises corn starch, and / or sodium starch glycolate, and / or cross-linked sodium carboxymethyl cellulose.

[0020] Preferably, the lubricant is magnesium stearate, and the glidant is one of silicon dioxide and talc.

[0021] Preferably, in the present invention, the ibuprofen particle size distribution D 50 ≤70μm.

[0022] Preferably, in the present invention, the hardness of the composite zinc cloth sheet is preferably 80 to 110N.

[0023] The beneficial effects of the present invention are:

[0024] The product prepared by the method of the present invention has good quality stability and dissolution effect, and the process is common and suitable for commercial production. DETAILED DESCRIPTION

[0025] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0026] Example 1

[0027] Table 1 Raw materials of compound zinc cloth sheet

[0028]

[0029] Preparation method:

[0030] S1. Weigh each raw material according to the amount of each component in Table 1, crush and sieve each raw material, pass zinc gluconate and chlorpheniramine maleate through an 80-mesh sieve, and select ibuprofen particle size distribution D 50 ≤70μm;

[0031] S2. The adhesive was made of corn starch, dextrin and purified water to form a 7% mixed paste for use as an adhesive;

[0032] S3 were taken zinc gluconate, ibuprofen, chlorpheniramine maleate, corn starch, lactose, 1 / 2 the amount of sodium starch glycolate, dry mix; then add a binder to make a soft material, the material; using 18 mesh nylon mesh swing granulation;

[0033] The particles are passed through a fluidized bed with an air inlet temperature of 75°C to dry the wet particles. After drying, the moisture content of the particles is ≤2.5%. The dry particles are sized to 18 mesh.

[0034] S4. After granulation, the granules are evenly mixed with the remaining 1 / 2 amount of sodium carboxymethyl starch, magnesium stearate, and silicon dioxide, and tableted. The tablet hardness is controlled to 80N to 110N to obtain compound zinc cloth tablets.

[0035] Example 2

[0036] Table 2 Raw materials of compound zinc cloth sheet

[0037]

[0038]

[0039] The preparation method is the same as that of Example 1.

[0040] Example 3

[0041] Table 3 Raw materials of compound zinc cloth sheet

[0042]

[0043] The preparation method is the same as that of Example 1.

[0044] Example 4

[0045] Table 4 Raw materials of compound zinc cloth sheet

[0046]

[0047]

[0048] The preparation method is the same as that of Example 1, and the batch size in each of the above cases is 1,300 tablets.

[0049] Test Example 1

[0050] The quality of the composite zinc cloth sheets prepared in Examples 1 to 4 was tested in accordance with WS1-(X-139)-2003Z.

[0051] Table 5 Test data of products in various embodiments

[0052]

[0053] Zinc gluconate and chlorpheniramine maleate are easily soluble in gastric acid, and their in vivo dissolution effects are better than ibuprofen. The dissolution rates in Table 5 are the dissolution test data of ibuprofen in 30 minutes.

[0054] Test Example 2

[0055] The compound zinc cloth sheets prepared in Examples 1 to 4 were subjected to stability tests.

[0056] Test conditions: Accelerated test for 6 months at high temperature of 40℃±2℃ and relative humidity of 75%±5% and long-term test for 18 months at temperature of 25℃±2℃ and relative humidity of 60%±5% to detect changes in various quality indicators.

[0057] Product inspection is based on WS1-(X-139)-2003Z.

[0058] Table 6 Accelerated 6-month data under high temperature 40℃±2℃ and relative humidity 75%±5%

[0059]

[0060] Table 7 18-month data under the conditions of temperature 25℃±2℃ and relative humidity 60%±5%

[0061]

[0062]

[0063] It can be seen from the above data that the quality of the compound zinc cloth sheet of the present invention is stable, ensuring that the product quality meets the quality standard requirements. In the accelerated test (high temperature 40°C ± 2°C, relative humidity 75% ± 5%), the quality indicators corresponding to 0 days for six months changed slightly. In the long-term test (temperature 25°C ± 2°C, relative humidity 60% ± 5%), the quality indicators corresponding to 0 days for 18 months did not change significantly, and the product quality tended to be stable.

[0064] Finally, it should be noted that the above-described embodiments are only specific implementation methods of the present invention, which are used to illustrate the technical solutions of the present invention rather than to limit them. The protection scope of the present invention is not limited thereto. Although the present invention has been described in detail with reference to the above-mentioned embodiments, ordinary technicians in this field should understand that any technician familiar with this technical field can still modify the technical solutions recorded in the above-mentioned embodiments within the technical scope disclosed by the present invention, or make equivalent replacements for some of the technical features therein; and these modifications, changes or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be covered by the protection scope of the present invention.

Claims

1. A method for preparing a composite zinc cloth sheet, characterized in that: The following steps are involved: S1. The zinc gluconate and chlorpheniramine maleate were crushed and sieved; S2. A 7%-8% mixed paste of corn starch, dextrin and purified water was prepared as a binder; S3. The crushed and sieved zinc gluconate and chlorpheniramine maleate, ibuprofen, filler and disintegrant were dry mixed, and after mixing, a binder was added for wet granulation; S4. After wet granulation, the particles are dried and sized, and then a disintegrant, a lubricant, and a glidant are added and mixed evenly, and tablets are pressed to obtain compound zinc cloth tablets.

2. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: Calculated by mass percentage, the raw material is 35%-45%, the filler is 45%-55%, the binder is 2%-5%, the disintegrant is 3%-7%, the lubricant is 0.5%-2%, and the glidant is 0.1%-1.5%.

3. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: The mass ratio of ibuprofen, zinc gluconate and chlorpheniramine maleate is 75:50:

1.

4. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: In step S2, the mass ratio of corn starch to dextrin is 3:1 to 3:

2.

5. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: The mass ratio of the disintegrant in step S3 to the disintegrant in step S4 is 1:

1.

6. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: The filler includes at least one of lactose, corn starch, microcrystalline cellulose, and dextrin.

7. The method for preparing a composite zinc cloth sheet according to claim 1, characterized in that: The disintegrant comprises at least one of corn starch, sodium starch glycolate and cross-linked sodium carboxymethyl cellulose.

8. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: The lubricant is magnesium stearate, and the glidant is one of silicon dioxide and talc.

9. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: The ibuprofen particle size distribution D 50 ≤70μm.

10. The method for preparing a composite zinc cloth sheet according to claim 1, wherein: Control tablet hardness to 80N~110N.

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