A film coating premix and its preparation method and application

Abstract

The present invention relates to a film coating premix and a preparation method thereof, wherein the film coating premix includes the following components by mass fraction: 50-100 parts of hydroxypropyl methylcellulose, 20-40 parts of microcrystalline cellulose, 10-30 parts of polyethylene glycol, 1-5 parts of triacetin, 1-8 parts of mannitol, 10-30 parts of modified silicon dioxide, and 1-10 parts of auxiliary agent; wherein the modified silicon dioxide is obtained by reacting silicon dioxide with a silane coupling agent and a fatty alcohol block polyether. The present invention adopts microcrystalline cellulose, hydroxypropyl methylcellulose, modified silicon dioxide and other components to prepare a film coating premix, wherein long alkyl, ethoxy and propoxy segments are introduced into the surface of the modified silicon dioxide, and after mixing with other materials, there is a good synergistic effect, and the various properties of the product are improved, so that the premix can be more durable and stably play a role.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical excipients, and in particular to a film coating premix, a preparation method and application thereof. Background Art

[0002] Film coating is a film layer coated on the surface of the drug, which has been widely used in tablets, pills, granules and other medicines. The use of film coating to wrap the drug is not only simple and fast, green and pollution-free, but also gives the drug a more beautiful and unique appearance, greatly improving production efficiency and reducing production costs; at the same time, film coating can realize the functions of moisture-proof, heat-resistant and odor-reducing drugs, thereby avoiding mildew, disintegration and other phenomena, and increasing the shelf life; film coating also has a wealth of additional functions, which can realize specific drug release positions and release characteristics according to different uses, different absorption sites and other requirements, further improving the efficacy of the drug.

[0003] It is a common process in the current industry to prepare film coating premixes using a specific process with multiple materials, and then further compress and wrap them. However, the current film coating premixes still have certain defects, such as the mixture is prone to agglomeration, unevenness, and insufficient stability, which affects the subsequent drug production and application and may cause product quality problems.

[0004] In summary, it is necessary to develop a new technical solution to solve the defects in the prior art. Summary of the invention

[0005] Based on this, the present invention provides a film coating premix, a preparation method and application thereof. The present invention adopts microcrystalline cellulose, hydroxypropyl methylcellulose, modified silicon dioxide and other ingredients to prepare a film coating premix, wherein long alkyl, ethoxy and propoxy chain segments are introduced on the surface of the modified silicon dioxide, which has good synergistic effect after mixing with other materials, improves various properties of the product, and enables the premix to play a role more persistently and stably.

[0006] One object of the present invention is to provide a film coating premix, wherein the film coating premix comprises the following components in parts by weight:

[0007]

[0008] Wherein, the modified silicon dioxide is obtained by reacting silicon dioxide with a silane coupling agent and a fatty alcohol block polyether.

[0009] Furthermore, the silane coupling agent is an epoxy silane coupling agent.

[0010] Furthermore, the auxiliary agent is selected from one or more of a dispersant, a binder, a lubricant, a disintegrant, a flavoring agent, an essence, a salt, and a pigment.

[0011] Preferably, the lubricant is sodium stearyl fumarate; and the binder is povidone K30.

[0012] Another object of the present invention is to provide a method for preparing the above-mentioned film coating premix, the method for preparing the film coating premix comprising the following steps:

[0013] S1. Blending silica and a silane coupling agent, heating and stirring the mixture to obtain an intermediate product;

[0014] S2. The intermediate product, fatty alcohol block polyether, and catalyst are blended and heated to react under an inert gas atmosphere to obtain modified silica;

[0015] S3, mixing microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin, mannitol, polyethylene glycol, adjuvants and the modified silicon dioxide, stirring evenly, grinding and sieving to obtain the film coating premix.

[0016] Furthermore, in step S1, the temperature of the heating and stirring reaction is 30-80°C and the time is 3-6h.

[0017] Furthermore, in step S2, the heating reaction temperature is 80-100° C. and the time is 24-72 hours.

[0018] Furthermore, in step S2, the catalyst is an alkali catalyst.

[0019] Furthermore, in step S3, the grinding and screening is 80-100 mesh.

[0020] Another object of the present invention is to provide use of the above-mentioned film coating premix in a pharmaceutical composition.

[0021] The present invention has the following beneficial effects:

[0022] The film coating premix provided by the present invention adopts materials such as hydroxypropyl methylcellulose and microcrystalline cellulose as main components and is compounded with modified silicon dioxide. The modified silicon dioxide is first treated with an epoxy silane coupling agent, an epoxy group is introduced on the surface of silicon dioxide, and then it is reacted with a fatty alcohol block polyether to obtain a product, thereby introducing long alkyl, EO, and PO segments on the surface of silicon dioxide. The modified silicon dioxide reduces the hydroxyl content with strong surface polarity, has better dispersibility, avoids the phenomenon of agglomeration and uneven dispersion, and the hydrophilic and hydrophobic segments introduced on the surface at the same time also make the modified silicon dioxide and microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin and other components more compatible, when preparing the coating layer, it is easy to be entangled and cross-linked with other ingredients, and a synergistic effect is exerted, thereby not only improving the film-forming property of the premix, but also improving the stability of the coating layer, so that the drug coating of the present invention can be stored under various conditions for a long time and stably, and has a good application prospect. DETAILED DESCRIPTION

[0023] In order to more clearly illustrate the technical solution of the present invention, the following examples are listed. Unless otherwise stated, the raw materials, reactions and post-treatment methods shown in the examples are common raw materials on the market and technical methods well known to those skilled in the art.

[0024] The words "preferred", "preferably", "more preferably", etc. in the present invention refer to embodiments of the present invention that can provide certain beneficial effects in certain circumstances. However, other embodiments may also be preferred under the same circumstances or other circumstances. In addition, the description of one or more preferred embodiments does not imply that other embodiments are not applicable, nor is it intended to exclude other embodiments from the scope of the present invention.

[0025] It should be understood that, except in any operating examples, or where otherwise indicated, all numbers indicating, for example, the amounts of ingredients used in the specification and claims should be understood to be modified in all cases by the term "about". Therefore, unless indicated to the contrary, the numerical parameters set forth in the following specification and the appended claims are approximate values ​​that vary depending on the desired properties to be obtained by the present invention.

[0026] The polyethylene glycol in the embodiment of the present invention is PEG-6000.

[0027] The silica particle size in the embodiment of the present invention is 10-20 nm.

[0028] The lauryl alcohol polyoxyethylene polyoxypropylene ether in the embodiment of the present invention is purchased from Haishihua, and has a molecular weight of 1500.

[0029] The "parts" in the embodiments of the present invention refer to parts by mass.

[0030] Example 1

[0031] A film coating premix, comprising the following components in parts by weight:

[0032]

[0033] The preparation method of the film coating premix comprises the following steps:

[0034] S1. Using ethanol as solvent, silica and KH560 were mixed in a mass ratio of 1:0.5, stirred at 60 ° C for 3 h, filtered, washed and dried to obtain an intermediate product;

[0035] S2. Under a nitrogen atmosphere, the intermediate product and lauryl alcohol polyoxyethylene polyoxypropylene ether in a mass ratio of 1:3 were blended, and then triethylamine (1 wt% of the reaction system) was added, and the reaction was stirred at 90 ° C for 48 h, and the modified silica was obtained after washing and drying;

[0036] S3. According to the above mass fractions, microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin, mannitol, polyethylene glycol, adjuvants and the modified silicon dioxide are mixed and stirred evenly, and ground through a 100-mesh sieve to obtain the film coating premix.

[0037] Example 2

[0038] A film coating premix, comprising the following components in parts by weight:

[0039]

[0040] The preparation method of the film coating premix comprises the following steps:

[0041] S1. Using ethanol as solvent, silica and KH560 were mixed in a mass ratio of 1:0.5, stirred at 60 ° C for 3 h, filtered, washed and dried to obtain an intermediate product;

[0042] S2. Under a nitrogen atmosphere, the intermediate product and lauryl alcohol polyoxyethylene polyoxypropylene ether in a mass ratio of 1:3 were blended, and then triethylamine (1 wt% of the reaction system) was added, and the reaction was stirred at 90 ° C for 48 h, and the modified silica was obtained after washing and drying;

[0043] S3. According to the above mass fractions, microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin, mannitol, polyethylene glycol, adjuvants and the modified silicon dioxide are mixed and stirred evenly, and ground through a 100-mesh sieve to obtain the film coating premix.

[0044] Example 3

[0045] A film coating premix, comprising the following components in parts by weight:

[0046]

[0047] The preparation method of the film coating premix comprises the following steps:

[0048] S1. Using ethanol as solvent, silica and KH560 were mixed in a mass ratio of 1:0.5, stirred at 60 ° C for 3 h, filtered, washed and dried to obtain an intermediate product;

[0049] S2. Under a nitrogen atmosphere, the intermediate product and lauryl alcohol polyoxyethylene polyoxypropylene ether in a mass ratio of 1:3 were blended, and then triethylamine (1 wt% of the reaction system) was added, and the reaction was stirred at 90 ° C for 48 h, and the modified silica was obtained after washing and drying;

[0050] S3. According to the above mass fractions, microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin, mannitol, polyethylene glycol, adjuvants and the modified silicon dioxide are mixed and stirred evenly, and ground through a 100-mesh sieve to obtain the film coating premix.

[0051] Comparative Example 1

[0052] A film coating premix, the difference between this comparative example and Example 1 is that the modified silicon dioxide is replaced by an equal mass of unmodified silicon dioxide, and the other ingredients and preparation method are the same as those of Example 1.

[0053] Comparative Example 2

[0054] A film coating premix, the difference between this comparative example and Example 1 is that the lauryl alcohol polyoxyethylene polyoxypropylene ether in step S2 is replaced by polyethylene glycol (PEG-1000) of equal mass, and the other ingredients and preparation method are the same as those in Example 1.

[0055] Test Case

[0056] The film coating premixes prepared in the examples and comparative examples were subjected to performance tests.

[0057] The test method is as follows:

[0058] The film coating premix prepared in the example and the comparative example were respectively mixed with an ethanol solution (ethanol: water = 6:4, v / v) at a solid content of 10 wt% to obtain a suspension, and then the vitamin C tablets were coated with 3% weight gain.

[0059] The obtained samples were placed at a temperature of 40° C. and a humidity of 80% for 15 days to detect whether the drug overflowed and the weight gain of the samples.

[0060] The test results are shown in Table 1.

[0061] Table 1 Performance test results

[0062] project Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 stability / % No overflow No overflow No overflow overflow overflow Weight gain / % 0.73 0.72 0.75 1.66 1.01 Disintegration qualified qualified qualified qualified qualified

[0063] According to Table 1, it can be concluded that the film coating premix prepared in Examples 1-3 of the present invention has good comprehensive performance, good stability under high temperature and high humidity environment, can prevent the drug components from overflowing, and achieve long-term storage. However, due to the replacement of modified silicon dioxide in Comparative Example 1-2, the stability of the product is reduced, and the weight gain due to moisture absorption is obvious. In summary, the film coating premix of the present invention has excellent performance, solves the defects existing in the prior art, and has good application prospects.

[0064] 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.

[0065] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A film coating premix, characterized in that: The film coating premix comprises the following components in parts by weight: Wherein, the modified silica is obtained by reacting silica with a silane coupling agent and a fatty alcohol block polyether; The preparation method of the film coating premix comprises the following steps: S1, mixing silicon dioxide and a silane coupling agent, heating and stirring to react, and obtaining an intermediate product; S2, blending the intermediate product, fatty alcohol block polyether and catalyst, and heating them under an inert gas atmosphere to react to obtain modified silicon dioxide; S3, mixing microcrystalline cellulose, hydroxypropyl methylcellulose, triacetin, mannitol, polyethylene glycol, adjuvants and the modified silicon dioxide, and grinding and sieving to obtain the film coating premix; The silane coupling agent is an epoxy silane coupling agent; The fatty alcohol block polyether is lauryl alcohol polyoxyethylene polyoxypropylene ether; The catalyst is triethylamine.

2. The film coating premix according to claim 1, characterized in that: The auxiliary agent is selected from one or more of a dispersant, a binder, a lubricant, a disintegrant, a flavoring agent, an essence, a salt, and a pigment.

3. The film coating premix according to claim 1, characterized in that: In step S1, the temperature of the heating and stirring reaction is 30-80°C and the time is 3-6h.

4. The film coating premix according to claim 1, characterized in that: In step S2, the heating reaction is carried out at a temperature of 80-100°C and for a time of 24-72 hours.

5. The film coating premix according to claim 1, characterized in that: In step S3, the grinding and screening is 80-100 mesh.

6. Use of the film coating premix according to any one of claims 1 to 5 in the preparation of a pharmaceutical composition.

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