Multi-effect synergistic innovative coating material and preparation method thereof

Abstract

The invention is applied to the technical field of pharmaceutic adjuvants, and discloses a multi-effect synergistic innovative coating material which comprises the following components in percentage by weight: 13%-26% of hydroxypropyl methylcellulose, 10%-16% of polyethylene glycol, 0.07%-0.15% of dimeticone, 15%-21% of titanium dioxide, 38%-46% of talcum powder, 3.5%-7.6% of ethyl acrylate-methacrylic acid copolymer aqueous dispersion, 0.7%-2.0% of iron oxide red and 0.6%-1.05% of iron oxide yellow. According to the multi-effect synergistic innovative coating material, synergistic optimization of functions of film forming, shading, moisture prevention, drug release regulation, adhesion resistance, defoaming and the like is achieved by precisely regulating the proportion of all the components, a composite film forming system is formed by hydroxypropyl methylcellulose and an ethyl acrylate-methacrylic acid copolymer aqueous dispersion, the film forming effect is synergistically achieved, and the coating material has the advantages that the coating material has a good application prospect. The compactness of the coating layer is ensured, and the acid resistance and the stability of the coating layer are improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical excipients technology, specifically to a multi-effect synergistic innovative coating material and its preparation method. This coating material is particularly suitable for coating formulations such as tablets and granules that have high requirements for stability, photosensitivity and drug release regulation. Background Technology

[0002] Coating technology is one of the key technologies in the field of pharmaceutical formulation. By coating a drug formulation with a thin film, multiple functions can be achieved, such as light protection, moisture protection, taste masking, improved appearance, and regulation of drug release. However, existing coating materials often suffer from single function and poor synergy: some coating materials have basic film-forming properties, but their light-blocking effect is poor, which makes photosensitive drugs prone to degradation during storage. Some materials have good light-blocking properties, but the film is brittle after formation and is prone to cracking and peeling. Some coating materials are difficult to balance the stability of release rate and bioavailability when regulating drug release, and the coating process is prone to problems such as adhesion and excessive foaming. Currently, most commonly used coating materials on the market use a single polymer as the film-forming substrate, combined with a small amount of excipients. For example, when hydroxypropyl methylcellulose is used alone as the film-forming agent, the moisture resistance and mechanical strength of the coating film are insufficient. When acrylic resin materials are used, although the drug release performance can be controlled, a large amount of anti-sticking agent needs to be added during the film-forming process, which can easily lead to uneven coating film. In addition, the proportion of each component in existing coating materials is not designed reasonably, which often leads to mutual interference between different functions and makes it difficult to achieve multi-effect synergy. For example, although the addition of plasticizer can improve the flexibility of the coating film, excessive addition will affect the density of the coating film. The poor compatibility between light-blocking agents and film-forming agents will reduce the integrity of the coating film, thereby affecting the storage stability and drug release consistency of the drug. Therefore, developing an innovative coating material that combines excellent film-forming properties, light-shielding properties, moisture-proof properties, and drug release regulation functions, with good synergistic effects among its components and a stable coating process, has become an urgent technical problem to be solved in the field of pharmaceutical excipients. Summary of the Invention

[0003] The purpose of this invention is to provide a multi-effect synergistic innovative coating material and its preparation method, so as to solve the problems mentioned in the background art, such as the single function of existing coating materials, poor synergy of components, poor light-blocking and moisture-proof effects, insufficient film stability, and prominent coating process problems.

[0004] To achieve the above objectives, the present invention provides the following technical solution: a multi-effect synergistic innovative coating material, comprising the following components by weight percentage: hydroxypropyl methylcellulose 13%-26%, polyethylene glycol 10%-16%, dimethicone oil 0.07%-0.15%, titanium dioxide 15%-21%, talc 38%-46%, ethyl acrylate-methacrylic acid copolymer aqueous dispersion 3.5%-7.6%, iron oxide red 0.7%-2.0%, and iron oxide yellow 0.6%-1.05%.

[0005] Preferably, the components and their contents by weight percentage are: hydroxypropyl methylcellulose 19%-26%, polyethylene glycol 10%-14%, dimethicone oil 0.05%-0.15%, titanium dioxide 15%-17.5%, talc 38%-46%, ethyl acrylate-methacrylic acid copolymer aqueous dispersion 3.5%-5.3%, iron oxide red 1.4%-2.0%, and iron oxide yellow 0.9%-1.05%.

[0006] By adopting the above technical solution and optimizing the ratio range of each component, the film-forming base material and functional excipients achieve the best synergistic effect, which not only ensures the integrity and mechanical strength of the coating layer, but also significantly improves the comprehensive performance of light blocking, moisture protection and drug release regulation.

[0007] Preferably, the viscosity of the hydroxypropyl methylcellulose is 5-100 mPa·s, more preferably 5-15 mPa·s.

[0008] By adopting the above technical solution and selecting hydroxypropyl methylcellulose with a specific viscosity, it is helpful to form a dense and flexible coating film, avoiding the problem of poor flowability of the coating solution due to excessively high viscosity or insufficient coating film strength due to excessively low viscosity.

[0009] Preferably, the molecular weight of the polyethylene glycol is 4000-10000, and more preferably 6000-8000.

[0010] By adopting the above technical solution and controlling the molecular weight of polyethylene glycol within a certain range, its plasticizing effect can be fully utilized, effectively improving the flexibility and crack resistance of the coating film, while avoiding the adverse effects of excessively small or large molecular weight on the stability of the coating film.

[0011] Preferably, the solid content of the ethyl acrylate-methacrylic acid copolymer aqueous dispersion is 28%-40%.

[0012] By adopting the above technical solution, the precise control of solid content ensures the stability and film-forming efficiency of the aqueous dispersion, which is conducive to the formation of a continuous and uniform coating film and optimizes the operability of the coating process.

[0013] Preferably, the titanium dioxide is anatase or rutile, with a particle size of 0.1-0.5 μm.

[0014] By adopting the above technical solution, titanium dioxide with specific crystal form and particle size can maximize its light-blocking effect, while ensuring its good dispersion in the coating solution, and avoiding the decrease in light scattering efficiency or coating defects caused by excessive particle size or improper crystal form.

[0015] Preferably, the talc powder has a particle size of 5-20 μm, and more preferably 10-20 μm.

[0016] By adopting the above technical solution, controlling the particle size distribution of talc powder helps to improve the smoothness and anti-sticking properties of the coating layer, and enhance the mechanical strength of the coating film. Particle sizes that are too fine or too coarse will affect its functionality.

[0017] Preferably, the viscosity of the dimethicone oil is 100-500 mPa·s.

[0018] By adopting the above technical solution, the appropriate viscosity of dimethicone can effectively improve the leveling and defoaming effect of the coating solution, ensure a smooth and uniform coating film surface, and avoid dispersion difficulties caused by excessive viscosity.

[0019] A method for preparing a multi-effect synergistic innovative coating material includes the following steps: S1. Preparation of film-forming material: Add the prescribed amount of hydroxypropyl methylcellulose to purified water and stir for 20-30 minutes at 40-45℃ and 500-1000 rpm / min until completely dissolved. Add the prescribed amount of polyethylene glycol and continue stirring for 15-20 minutes to obtain the film-forming base solution. S2. Dispersion of functional components: Add the prescribed amounts of titanium dioxide, talc, iron oxide red, and iron oxide yellow to the film-forming base solution obtained in S1, heat to 50-60℃, and stir for 30-40 minutes at 600-1500 rpm / min to ensure uniform dispersion of solid components. S3. Construction of the composite system: Slowly add the prescribed amount of ethyl acrylate-methacrylic acid copolymer aqueous dispersion to the dispersion obtained in S2, and stir at 50-60℃ and 700-1500 rpm / min for 25-40 min. S4. Optimization and Adjustment: Add the prescribed amount of dimethicone, cool to 30-35℃, stir for 10-15 minutes at 600-1000 rpm / min, filter, and obtain the finished coating material.

[0020] Preferably, the filtration in step S4 is through a 200-mesh sieve. The method further includes quality testing of the finished product to ensure that the total number of microbial colonies is ≤10. 2 cfu / g, heavy metal content ≤20ppm.

[0021] By adopting the above technical solution and specifying filtration accuracy and strict quality control standards, we can ensure that the final product is free of impurities and microbial contamination, and meets the safety and stability requirements of pharmaceutical excipients.

[0022] Compared with the prior art, the beneficial effects of the present invention are: this multi-effect synergistic innovative coating material: 1. This invention achieves synergistic optimization of film-forming, light-shielding, moisture-proofing, drug release regulation, anti-adhesion, and defoaming functions by precisely controlling the proportions of each component. A composite film-forming system is formed by an aqueous dispersion of hydroxypropyl methylcellulose and ethyl acrylate-methacrylic acid copolymer, which synergistically exerts the film-forming effect, ensuring the density of the coating layer while improving its acid resistance and stability. Polyethylene glycol, as a plasticizer, has good compatibility with the film-forming agent and effectively improves the flexibility of the coating layer. The combination of titanium dioxide and talc provides excellent light-shielding effect, while preventing tablet sticking and improving the appearance quality of the coating. The precise dosage of dimethicone further optimizes the smoothness of the coating layer. The combination of iron oxide red and iron oxide yellow achieves ideal coloring effect with stable color, effectively protecting photosensitive drugs and improving the mechanical strength of the coating film. 2. The coating layer formed by the coating material prepared in this invention, when placed under high temperature (60℃) and high humidity (92.5% relative humidity) conditions for 10 days, shows a drug content change rate of ≤5%, no significant color change, and significantly lower hygroscopicity than conventional coating materials. It can effectively isolate external air and moisture, delay drug oxidation, and significantly extend the shelf life of drug preparations. 3. This invention adopts a stepwise stirring and gradient temperature control preparation method, which does not require complex equipment. The parameters of each step are clear, making it easy to scale up for industrial production. The particle size control of the sieving operation in the pretreatment stage ensures the uniformity of subsequent component dispersion and improves the stability of product quality. 4. The coating material of the present invention is widely used in the coating of various solid pharmaceutical preparations such as tablets, granules, and pills. All components are pharmaceutical-grade excipients, conforming to international standards such as USP / NF. It has good biocompatibility and no obvious toxic side effects. It is especially suitable for various unstable vitamins, antibiotics and other drugs with high stability requirements. It has excellent compatibility with amoxicillin granules and has good application prospects. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the method flow of the present invention. Detailed Implementation

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Please see Figure 1 This invention provides a technical solution: a multi-effect synergistic innovative coating material.

[0026] Example 1: An innovative, highly stable coating material, comprising the following components by weight percentage: 13% hydroxypropyl methylcellulose, 16% polyethylene glycol, 0.1% dimethicone, 21% titanium dioxide, 41% talc, 7.6% ethyl acrylate-methacrylic acid copolymer aqueous dispersion, 0.7% iron oxide red, and 0.6% iron oxide yellow.

[0027] Preparation method: (1) Preparation of film-forming material: Weigh 13% of the prescribed amount of hydroxypropyl methylcellulose and add it to an appropriate amount of purified water. Stir at 40℃ and 700rpm / min for 30min until completely dissolved. Add 16% of the prescribed amount of polyethylene glycol and continue stirring for 20min to form a film-forming base solution.

[0028] (2) Functional dispersion: Add 21% of titanium dioxide, 41% of talc, 0.7% of iron oxide red and 0.6% of iron oxide yellow in the prescription to the film-forming base solution, heat to 50°C, increase the stirring speed to 1000 rpm / min, and stir for 40 min.

[0029] (3) Construction of composite system: Slowly add 7.6% of the prescribed amount of ethyl acrylate-methacrylic acid copolymer aqueous dispersion (solid content 30%), and stir at 50℃ and 1000rpm / min for 35min.

[0030] (4) Optimization and adjustment: Add 0.1% of dimethicone oil according to the prescription, cool down to 30°C, reduce the stirring speed to 600 rpm / min, stir for 15 min, filter through a 200-mesh sieve to obtain the finished coating material.

[0031] (5) Quality inspection: The total number of microbial colonies in the finished product was 8 cfu / g and the heavy metal content was 12 parts per million, which met the quality standards.

[0032] Example 2: An innovative, highly stable coating material, by weight percentage, comprises the following components: 19% hydroxypropyl methylcellulose, 14% polyethylene glycol, 0.05% dimethicone, 15% titanium dioxide, 46% talc, 3.5% ethyl acrylate-methacrylic acid copolymer aqueous dispersion, 1.4% iron oxide red, and 1.05% iron oxide yellow.

[0033] Preparation method: (1) Preparation of film-forming material: Weigh 19% of the prescribed amount of hydroxypropyl methylcellulose and add it to an appropriate amount of purified water. Stir at 40℃ and 700 rpm for 30 min until completely dissolved. Add 14% of the prescribed amount of polyethylene glycol and continue stirring for 20 min to form a film-forming base solution.

[0034] (2) Functional dispersion: Add 15% of titanium dioxide, 46% of talc, 1.4% of iron oxide red and 1.05% of iron oxide yellow to the film-forming base solution, heat to 50°C, increase the stirring speed to 1000 rpm / min, and stir for 40 min.

[0035] (3) Construction of composite system: Slowly add 3.5% of the prescribed amount of ethyl acrylate-methacrylic acid copolymer aqueous dispersion (solid content 30%), and stir at 50℃ and 1000rpm / min for 35min.

[0036] (4) Optimization and adjustment: Add 0.05% dimethicone oil, cool down to 30°C, reduce the stirring speed to 600 rpm / min, stir for 15 min, filter through a 200-mesh sieve to obtain the finished coating material.

[0037] (5) Quality inspection: The total number of microbial colonies in the finished product was 6 cfu / g and the heavy metal content was 12 parts per million, which met the quality standards.

[0038] Example 3 An innovative, highly stable coating material comprises, by weight percentage, the following components: 26% hydroxypropyl methylcellulose, 10% polyethylene glycol, 0.15% dimethicone, 17.5% titanium dioxide, 38% talc, 5.3% ethyl acrylate-methacrylic acid copolymer aqueous dispersion, 2.0% iron oxide red, and 1.05% iron oxide yellow.

[0039] Preparation method: (1) Preparation of film-forming material: Weigh 26% of the prescribed amount of hydroxypropyl methylcellulose and add it to an appropriate amount of purified water. Stir at 40℃ and 700 rpm for 30 min until completely dissolved. Add 10% of the prescribed amount of polyethylene glycol and continue stirring for 20 min to form a film-forming base solution.

[0040] (2) Functional dispersion: Add 17.5% of titanium dioxide, 38% of talc, 2.0% of iron oxide red and 1.05% of iron oxide yellow to the film-forming base solution, heat to 50°C, increase the stirring speed to 1000 rpm / min, and stir for 40 min.

[0041] (3) Construction of composite system: Slowly add 5.3% of the prescribed amount of ethyl acrylate-methacrylic acid copolymer aqueous dispersion (solid content 30%), and stir at 50℃ and 1000rpm / min for 35min.

[0042] (4) Optimization and adjustment: Add 0.15% dimethicone oil, cool down to 30°C, reduce the stirring speed to 600 rpm / min, stir for 15 min, filter through a 200-mesh sieve to obtain the finished coating material.

[0043] (5) Quality testing: The total number of microbial colonies in the finished product was 12 cfu / g and the heavy metal content was 18 parts per million, which met the quality standards. The coating material prepared in this embodiment was used to coat phenacetin tablets. The coating process parameters were: inlet air temperature 40-50℃, outlet air temperature 30-40℃, peristaltic pump spray speed 1-2 rpm, spray speed 1-3 mL / min, pot rotation speed 5-10 rpm / min. The weight gain after coating was 2%-4%. The coated phenacetin tablets had good fluidity, no abrasion, fragments, or adhesion. After being placed under high temperature (60℃), high humidity (25℃, relative humidity 92.5%), and light (4500±500 Lx & 85 μw / cm2) conditions for 30 days, the content change rate of the phenacetin coated tablets under light conditions was only 98.9%, which was significantly better than the conventional coated tablets with a content of 80.3% (content change rate 18.6%).

[0044] Performance testing The stability of the coating materials prepared in Examples 1-3 above was tested. These materials were used to coat perphenazine tablets, with a conventional coating material serving as a control group. Accelerated (40℃ / 75%RH, 6 months) and influencing factors including high temperature (60℃), high humidity (25℃, 92.5%RH), and light exposure (4500±500Lx & 85μw / cm2) tests were conducted. The changes in content, related substances, and color of perphenazine-coated tablets and conventionally coated tablets after 30 days under both accelerated and accelerated conditions were investigated. The results are shown in the table below: Influencing factors - 30 days of high temperature (60℃) Influencing factors - 30 days of high humidity (25℃, relative humidity 92.5%RH) Influencing factors - 30-day light exposure (4500±500 Lx & 85 μw / cm2) 6-month accelerated trial Data Analysis: The stability data in the table above shows the stability results of Examples 1, 2, and 3. The formulation exhibited excellent performance under various influencing factors, including 30 days of high temperature (60°C), 30 days of high humidity (25°C, 92.5%RH), 30 days of light exposure (4500±500Lx & 85μw / cm²), and a 6-month accelerated testing process. This fully demonstrates that the coating technology possesses good stability, and excellent coating performance is achieved through precise control of the coating material composition.

[0045] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A multi-effect synergistic innovative coating material, characterized in that: By weight percentage, it comprises the following components: hydroxypropyl methylcellulose 13%-26%, polyethylene glycol 10%-16%, dimethicone 0.07%-0.15%, titanium dioxide 15%-21%, talc 38%-46%, ethyl acrylate-methacrylic acid copolymer aqueous dispersion 3.5%-7.6%, iron oxide red 0.7%-2.0%, and iron oxide yellow 0.6%-1.05%.

2. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The preferred components and their contents by weight percentage are: hydroxypropyl methylcellulose 19%-26%, polyethylene glycol 10%-14%, dimethicone 0.05%-0.15%, titanium dioxide 15%-17.5%, talc 38%-46%, ethyl acrylate-methacrylic acid copolymer aqueous dispersion 3.5%-5.3%, iron oxide red 1.4%-2.0%, and iron oxide yellow 0.9%-1.05%.

3. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The viscosity of the hydroxypropyl methylcellulose is 5-100 mPa·s, preferably 5-15 mPa·s.

4. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The molecular weight of the polyethylene glycol is 4000-10000, preferably 6000-8000.

5. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The solid content of the aqueous dispersion of the ethyl acrylate-methacrylic acid copolymer is 28%-40%.

6. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The titanium dioxide is anatase or rutile, with a particle size of 0.1-0.5 μm.

7. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The talc powder has a particle size of 5-20 μm, preferably 10-20 μm.

8. The multi-effect synergistic innovative coating material according to claim 1, characterized in that: The viscosity of the dimethyl silicone oil is 100-500 mPa·s.

9. A method for preparing a multi-effect synergistic innovative coating material as described in any one of claims 1-8, characterized in that: Includes the following steps: S1. Preparation of film-forming material: Add the prescribed amount of hydroxypropyl methylcellulose to purified water and stir for 20-30 minutes at 40-45℃ and 500-1000 rpm / min until completely dissolved. Add the prescribed amount of polyethylene glycol and continue stirring for 15-20 minutes to obtain the film-forming base solution. S2. Dispersion of functional components: Add the prescribed amounts of titanium dioxide, talc, iron oxide red, and iron oxide yellow to the film-forming base solution obtained in S1, heat to 50-60℃, and stir for 30-40 minutes at 600-1500 rpm / min to ensure uniform dispersion of solid components. S3. Construction of the composite system: Slowly add the prescribed amount of ethyl acrylate-methacrylic acid copolymer aqueous dispersion to the dispersion obtained in S2, and stir at 50-60℃ and 700-1500 rpm / min for 25-40 min. S4. Optimization and Adjustment: Add the prescribed amount of dimethicone, cool to 30-35℃, and stir for 10-15 minutes at 600-1000 rpm / min to obtain the finished coating material.

10. The method for preparing a multi-effect synergistic innovative coating material according to claim 9, characterized in that: The filtration in step S4 involves passing the material through a 200-mesh sieve. The method also includes quality testing of the finished product to ensure a total microbial count ≤10. 2 cfu / g, heavy metal content ≤20ppm.

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