Application of coating premix in isosorbide mononitrate tablet and isosorbide mononitrate tablet

Abstract

The invention relates to an application of a coating premix in an isosorbide mononitrate tablet and the isosorbide mononitrate tablet. The coating premix is prepared from the following components in parts by weight: 40 to 60 parts of eudragit RS100, 20 to 30 parts of eudragit RL100, 10 to 15 parts of plasticizer, 15 to 20 parts of coloring agent, 15 to 20 parts of anti-sticking agent and 500 to 600 parts of solvent; the eudragit RS100 is prepared from ethyl acrylate, methyl methacrylate and methacrylic acid chlorinated trimethylamine ethyl ester; the eudragit RL100 is prepared from ethyl acrylate, methyl methacrylate and methacrylic acid chlorinated trimethylamine ethyl ester; through the application of the coating premix in the isosorbide mononitrate tablet, the technical problems that the existing isosorbide mononitrate tablet cannot be disintegrated and released after reaching the ileocecum of a human body, and the bioavailability of the medicine cannot be ensured are solved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to the application of a coating premix in isosorbide mononitrate tablets and isosorbide mononitrate tablets. Background Technology

[0002] Traditional oral or rectal administration not only has significant toxic side effects, but also suffers from poor specificity and is not well-tolerated by patients. In contrast, colon-targeted drug delivery directly delivers the drug to the affected area. Through a drug delivery system, the drug is not released in the digestive tract after oral administration, but is delivered to the ileocecal junction where it begins to disintegrate and be released, exerting a local or systemic therapeutic effect in the large intestine. This can improve efficacy or reduce dosage, while also reducing adverse reactions and making it more convenient for patients to use.

[0003] Isosorbide mononitrate tablets have the effects of clearing heat and detoxifying, cooling blood and stopping bleeding. They are used for dysentery, enteritis, hemoptysis, hematuria, hematochezia, metrorrhagia, carbuncles and boils. However, existing isosorbide mononitrate tablets cannot effectively reach the ileocecal junction of the human body before disintegrating and releasing, thus failing to guarantee the bioavailability of the drug by the human body.

[0004] Therefore, in view of the above problems, the present invention urgently needs to provide an application of a coating premix in isosorbide mononitrate tablets and isosorbide mononitrate tablets. Summary of the Invention

[0005] The purpose of this invention is to provide an application of a coating premix in isosorbide mononitrate tablets and isosorbide mononitrate tablets. By applying the coating premix to isosorbide mononitrate tablets, the problem that existing isosorbide mononitrate tablets cannot disintegrate and release only after reaching the ileocecal region of the human body, thus failing to guarantee the bioavailability of the drug, is solved.

[0006] The present invention provides an application of a coating premix in isosorbide mononitrate tablets. The coating premix comprises, by weight, 40-60 parts of Eucerin RS100, 20-30 parts of Eucerin RL100, 10-15 parts of plasticizer, 15-20 parts of colorant, 15-20 parts of anti-adhesion agent and 500-600 parts of solvent. UTEC RS100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1. UTEC RL100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0007] Preferably, the solvent is 80 wt.% ethanol.

[0008] Preferably, the plasticizer is one or more of polyethylene glycol 6000, triethyl citrate, glycerol, or propylene glycol.

[0009] Preferably, the colorant is one or more of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, or carmine aluminum lake.

[0010] Preferably, the anti-adhesion agent is one or more of talc, glyceryl monostearate, or magnesium stearate.

[0011] Preferably, the talc powder has an average particle size of 4-5 μm and a whiteness of 94.

[0012] Preferably, the polyethylene glycol 6000 has a viscosity of 5.5-9.0 mm. 2 / s, pH 6; Preferably, the relative density of triethyl citrate is 1.1389.

[0013] The present invention also provides isosorbide mononitrate tablets, comprising isosorbide mononitrate tablets, wherein the surface of the isosorbide mononitrate tablets is coated with a coating premix as described in any one of the above.

[0014] The application of a coating premix provided by this invention in isosorbide mononitrate tablets and the following improvements of isosorbide mononitrate tablets compared with the prior art: The coating premix provided by this invention, when used in tamsulosin hydrochloride sustained-release tablets, utilizes Eutec RS100 and Eutec RL100. Eutec RS100 and Eutec RL100 are water-insoluble film-forming materials that swell in water. They are cationic polymers composed of ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride. The molar ratio of these three components in Eutec RS100 is 1:2:0.1, while in Eutec RL100 it is 1:2:0.2. The content of quaternary ammonium salt groups determines the swelling and permeability of the coating in water. Eutec RS100 contains quaternary ammonium salts... With a low content of salt groups, it has low permeability and swelling, and the coating it forms can effectively block drug release. Eutrich RL100 has a high content of quaternary ammonium salt groups, resulting in greater permeability and swelling. It can be used in conjunction with Eutrich RS to regulate the drug release rate of the coated formulation. The drug is mainly released through diffusion via the hydrophilic pores formed by the quaternary ammonium salt groups in the coating. By adjusting the pore size of the release layer through the formulation of Eutrich RL100 and Eutrich RS100, the release rate of the chip drug can be controlled. This effectively enables the drug to begin disintegration and release after reaching the ileocecal junction, allowing for better bioavailability of the drug by the human body. Detailed Implementation

[0015] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, 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.

[0016] This invention provides an application of a coating premix in isosorbide mononitrate tablets. The coating premix comprises, by weight, 40-60 parts of Eucerin RS100, 20-30 parts of Eucerin RL100, 10-15 parts of plasticizer, 15-20 parts of colorant, 15-20 parts of anti-adhesion agent, and 500-600 parts of solvent. UTEC RS100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1. UTEC RL100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0017] Specifically, the solvent is 80 wt.% ethanol.

[0018] Specifically, the plasticizer is one or more of polyethylene glycol 6000, triethyl citrate, glycerol, or propylene glycol.

[0019] Specifically, the colorant is one or more of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, or carmine aluminum lake.

[0020] Specifically, the anti-adhesion agent is one or more of talc, glyceryl monostearate, or magnesium stearate.

[0021] Specifically, the average particle size of talc is 4-5 μm, and its whiteness is 94.

[0022] Specifically, polyethylene glycol 6000 has a viscosity of 5.5-9.0 mm. 2 / s, pH 6; Specifically, the relative density of triethyl citrate is 1.1389.

[0023] The present invention also provides isosorbide mononitrate tablets, comprising isosorbide mononitrate tablets, wherein the surface of the isosorbide mononitrate tablets is coated with a coating premix as described in any one of the above.

[0024] The coating premix provided by this invention is used in tamsulosin hydrochloride sustained-release tablets. It utilizes Eutrich RS100 and Eutrich RL100, which are water-insoluble film-forming materials that swell in water. They are cationic polymers composed of ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride. The molar ratio of these three components in Eutrich RS100 is 1:2:0.1, while in Eutrich RL100 it is 1:2:0.2. The content of quaternary ammonium salt groups determines the swelling and permeability of the coating in water. The low content of quaternary ammonium salt groups in Eucerin RS100 results in less permeability and swelling, and its coating effectively inhibits drug release. The high content of quaternary ammonium salt groups in Eucerin RL100 results in greater permeability and swelling, and it can be used in combination with Eucerin RS to regulate the drug release rate of the coated formulation. Drugs are primarily released through diffusion via hydrophilic pores formed by the quaternary ammonium salt groups in the coating. By adjusting the pore size of the release layer through the combination of Eucerin RL100 and Eucerin RS100, the release rate of the chip drug can be controlled. This effectively enables the drug to disintegrate and be released after reaching the ileocecal junction, facilitating the bioavailability of the drug by the human body.

[0025] The sustained-release premix proposed in this invention, Eutrapeptide RL / RS, is insoluble in water but can swell to form channels in the coating. The channel diameter of Eutrapeptide RL is 1-5 μm, and that of Eutrapeptide RS is 0.1-0.6 μm. Through a reasonable ratio, the drug release rate can be effectively controlled.

[0026] Example 1 Preparation process of coating premix for isosorbide mononitrate tablets: According to the weight percentages, 40 parts of Euterich RS100, 20 parts of Euterich RL100, 10 parts of plasticizer, 15 parts of colorant, and 15 parts of anti-sticking agent were poured into a mixer and mixed at room temperature for 1 hour. Then, 550 parts of solvent were added and the mixture was stirred for another 30 minutes. The resulting mixture was dried at 35°C for 5 hours. A sample was taken for testing, and the moisture content was found to be ≤8%, which was considered qualified. After passing the test, the mixture was ground and sieved to obtain a coating premix for isosorbide mononitrate tablets. Among them, Eutetech RS100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1; Eutetech RL100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0027] The solvent in this embodiment is 80 wt.% ethanol.

[0028] In this embodiment, the plasticizers are polyethylene glycol 6000 and propylene glycol, with a mass ratio of 1:1.

[0029] The colorants in this embodiment are Sunset Yellow aluminum lake and Carmine aluminum lake, with a mass ratio of Sunset Yellow aluminum lake to Carmine aluminum lake of 1:1.

[0030] The anti-adhesion agent in this embodiment is magnesium stearate.

[0031] The talc powder in this embodiment has an average particle size of 4-5 μm and a whiteness of 94.

[0032] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5-9.0 mm. 2 / s, pH 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0033] The coating premix for isosorbide mononitrate tablets was mixed with isosorbide mononitrate tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the isosorbide mononitrate tablets to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0034] Example 2 Preparation process of coating premix for isosorbide mononitrate tablets: According to the weight percentages, 60 parts of Eucerin RS100, 20-30 parts of Eucerin RL100, 15 parts of plasticizer, 20 parts of colorant, and 20 parts of anti-adhesion agent are poured into a mixer and mixed at room temperature for 1 hour. Then, 500 parts of solvent are added and the mixture is stirred for another 30 minutes. The resulting mixture is dried at 45°C for 5 hours. Samples are taken for testing, and the moisture content is ≤8%, which is considered qualified. After passing the test, the mixture is ground and sieved to obtain a coating premix for isosorbide mononitrate tablets. Among them, Eutetech RS100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1; Eutetech RL100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0035] The solvent in this embodiment is 80 wt.% ethanol.

[0036] In this embodiment, the plasticizers are triethyl citrate and propylene glycol, with a mass ratio of triethyl citrate to propylene glycol of 1:1.

[0037] The colorant in this embodiment is titanium dioxide.

[0038] The anti-adhesion agent in this embodiment is glyceryl monostearate.

[0039] The talc powder in this embodiment has an average particle size of 4-5 μm and a whiteness of 94.

[0040] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5-9.0 mm. 2 / s, pH 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0041] The coating premix for isosorbide mononitrate tablets was mixed with isosorbide mononitrate tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the isosorbide mononitrate tablets to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0042] Example 3 Preparation process of coating premix for isosorbide mononitrate tablets: According to the weight percentages, 50 parts of Euterich RS100, 25 parts of Euterich RL100, 12 parts of plasticizer, 17 parts of colorant, and 17 parts of anti-sticking agent were poured into a mixer and mixed at room temperature for 1 hour. Then, 600 parts of solvent were added and the mixture was stirred for another 30 minutes. The resulting mixture was dried at 40°C for 5 hours. A sample was taken for testing, and the moisture content was found to be ≤8%, which was considered qualified. After passing the test, the mixture was ground and sieved to obtain a coating premix for isosorbide mononitrate tablets. Among them, Eutetech RS100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1; Eutetech RL100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0043] The solvent in this embodiment is 80 wt.% ethanol.

[0044] The plasticizer in this embodiment is triethyl citrate.

[0045] The colorants in this embodiment are titanium dioxide and lemon yellow aluminum lake.

[0046] The anti-adhesion agents in this embodiment are talc and glyceryl monostearate.

[0047] The talc powder in this embodiment has an average particle size of 4-5 μm and a whiteness of 94.

[0048] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5-9.0 mm.2 / s, pH 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0049] The coating premix for isosorbide mononitrate tablets was mixed with isosorbide mononitrate tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the isosorbide mononitrate tablets to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0050] Example 4 Preparation process of coating premix for isosorbide mononitrate tablets: Coating premixes include an enteric coating layer and a moisture-proof layer; The enteric coating is prepared by mixing 50 parts by weight of Eutrich RS100, 25 parts by weight of Eutrich RL100, 12 parts by weight of plasticizer, 17 parts by weight of colorant, and 17 parts by weight of anti-sticking agent in a mixer. The mixture is stirred at room temperature for 1 hour, then 600 parts by weight of solvent is added and stirred for another 30 minutes. The resulting mixture is dried at 40°C for 5 hours. A sample is taken for testing, and the moisture content is found to be ≤8%, which is considered acceptable. After passing the test, the mixture is ground and sieved to obtain the enteric coating. The moisture-proof layer, by weight, comprises 50 parts hydroxypropyl methylcellulose, 75 parts cellulose acetate, 50 parts ethyl cellulose and 50 parts chitosan mixed together, with anhydrous ethanol added to obtain the moisture-proof layer.

[0051] Among them, Eutetech RS100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.1; Eutetech RL100 includes ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.2.

[0052] The solvent in this embodiment is 80 wt.% ethanol.

[0053] The plasticizer in this embodiment is triethyl citrate.

[0054] The colorants in this embodiment are titanium dioxide and lemon yellow aluminum lake.

[0055] The anti-adhesion agents in this embodiment are talc and glyceryl monostearate.

[0056] The talc powder in this embodiment has an average particle size of 4-5 μm and a whiteness of 94.

[0057] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5-9.0 mm. 2 / s, pH 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0058] The enteric coating layer and isosorbide mononitrate tablets were mixed at a mass ratio of 1:9. The enteric coating layer was coated on the outer surface of the isosorbide mononitrate tablets. The isosorbide mononitrate tablets coated with the enteric coating layer and the moisture-proof layer were mixed at a mass ratio of 1:9 to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0059] Comparative Example 1 The only difference between this comparative example and Example 1 is that Eutechi RS100 was not added. The coating premix of isosorbide mononitrate tablets was mixed with isosorbide mononitrate tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the isosorbide mononitrate tablets to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0060] Comparative Example 2 The only difference between this comparative example and Example 1 is that it does not contain Eutrapeptide RL100. The coating premix of isosorbide mononitrate tablets and isosorbide mononitrate tablets are mixed at a mass ratio of 1:9. The coating premix is ​​coated on the outer surface of the isosorbide mononitrate tablets to obtain isosorbide mononitrate tablets. The release rate is shown in Table 1.

[0061] Comparative Example 3 This comparative example is isosorbide mononitrate tablets without coating premix, and the release rate is shown in Table 1.

[0062] Table 1. Release rate of isosorbide mononitrate tablets

[0063] Compared to Example 1, Comparative Example 1 showed a 62% release rate in intestinal fluid after 7 hours, which was significantly lower than Example 1 due to the absence of Eutrich RS100. This demonstrates that the addition of Eutrich RS100 has a significant impact on the overall release rate.

[0064] Compared to Example 1, Comparative Example 2 showed a 61% release rate in intestinal fluid after 7 hours, which was significantly lower than that of Example 1 due to the absence of Eutrapept RL100. This demonstrates that the addition of Eutrapept RL100 has a significant impact on the overall release rate.

[0065] Comparative Example 3, without coating, showed partial release in gastric juice and 50% release in intestinal juice after 7 hours. This demonstrates that the coating premix of the present invention can effectively control the release of isosorbide mononitrate tablets.

[0066] Although the coating in Example 3 allows isosorbide mononitrate tablets to be released only after reaching the ileocecal region, these tablets are easily affected by moisture during storage, impacting their final efficacy. Example 4 incorporates a moisture-proof layer design. This layer, made from a mixture of hydroxypropyl methylcellulose, cellulose acetate, 50 parts ethyl cellulose, and chitosan, effectively protects the enteric coating. Furthermore, by controlling the proportions of these components, the dissolution rate in the stomach can be optimized, ensuring the final drug release within the ileocecal region and improving efficacy. The data also show that the moisture-proof layer did not affect the release rate of the isosorbide mononitrate tablets.

[0067] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of a coating premix in isosorbide mononitrate tablets, characterized in that: By weight, the coating premix comprises 40-60 parts of Eutechi RS100, 20-30 parts of Eutechi RL100, 10-15 parts of plasticizer, 15-20 parts of colorant, 15-20 parts of anti-sticking agent and 500-600 parts of solvent. UTEC RS100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.

1. UTEC RL100 comprises ethyl acrylate, methyl methacrylate, and trimethylaminoethyl methacrylate chloride, with a mass ratio of 1:2:0.

2.

2. The application of the coating premix according to claim 1 in isosorbide mononitrate tablets, characterized in that: The solvent is 80 wt.% ethanol.

3. The application of the coating premix according to claim 1 in isosorbide mononitrate tablets, characterized in that: The plasticizer is one or more of polyethylene glycol 6000, triethyl citrate, glycerol, or propylene glycol.

4. The application of the coating premix according to claim 1 in isosorbide mononitrate tablets, characterized in that: The colorant is one or more of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, or carmine aluminum lake.

5. The application of the coating premix according to claim 1 in isosorbide mononitrate tablets, characterized in that: The anti-adhesion agent is one or more of talc, glyceryl monostearate, or magnesium stearate.

6. The application of the coating premix according to claim 5 in isosorbide mononitrate tablets, characterized in that: The average particle size of talc is 4-5 μm, and its whiteness is 94.

7. The application of the coating premix according to claim 3 in isosorbide mononitrate tablets, characterized in that: Polyethylene glycol 6000, viscosity 5.5-9.0 mm. 2 / s, pH 6.

8. The application of the coating premix according to claim 3 in isosorbide mononitrate tablets, characterized in that: The relative density of triethyl citrate is 1.1389.

9. A tablet of isosorbide mononitrate, characterized in that: The invention includes isosorbide mononitrate tablets, wherein the surface of the isosorbide mononitrate tablets is coated with a coating premix as described in any one of claims 1-8.

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