Application of coating premix in tamsulosin hydrochloride sustained release tablet and tamsulosin hydrochloride sustained release tablet

Abstract

The invention relates to application of a coating premix in tamsulosin hydrochloride sustained-release tablets and the tamsulosin hydrochloride sustained-release tablets. 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 comprises ethyl acrylate, methyl methacrylate and methacrylic acid chlorinated trimethylamino ethyl ester, and the eudragit RL100 comprises ethyl acrylate, methyl methacrylate and methacrylic acid chlorinated trimethylamino ethyl ester; through application of the coating premix in the tamsulosin hydrochloride sustained-release tablet, the problems that the existing tamsulosin hydrochloride sustained-release tablet cannot be dissolved in the intestinal tract 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 tamsulosin hydrochloride sustained-release tablets and tamsulosin hydrochloride sustained-release 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 therapeutic effect locally or systemically 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] Tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release tablets cannot effectively disintegrate and release the drug after reaching the ileocecal junction, thus failing to guarantee full absorption and utilization of the drug by the body.

[0004] Therefore, in view of the above problems, the present invention urgently needs to provide an application of a coating premix in tamsulosin hydrochloride sustained-release tablets and tamsulosin hydrochloride sustained-release tablets. Summary of the Invention

[0005] The purpose of this invention is to provide an application of a coating premix in tamsulosin hydrochloride sustained-release tablets and tamsulosin hydrochloride sustained-release tablets. By using a coating premix in tamsulosin hydrochloride sustained-release tablets, the problem that existing tamsulosin hydrochloride sustained-release tablets cannot effectively achieve disintegration and release after reaching the ileocecal region of the human body, and cannot guarantee the full absorption and utilization of the drug by the human body is solved.

[0006] The present invention provides an application of a coating premix in tamsulosin hydrochloride sustained-release tablets. The coating premix comprises, by weight, 40-60 parts of Eutrich RS100, 20-30 parts of Eutrich 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 in 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.

[0013] Preferably, the relative density of triethyl citrate is 1.1389.

[0014] The present invention also provides a tamsulosin hydrochloride sustained-release tablet, comprising a tamsulosin hydrochloride sustained-release tablet, wherein the surface of the tamsulosin hydrochloride sustained-release tablet is coated with a coating premix as described in any one of the above.

[0015] The application of a coating premix provided by this invention in tamsulosin hydrochloride sustained-release tablets and the following improvements of tamsulosin hydrochloride sustained-release tablets compared with the prior art: 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 conjunction 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, allowing for full absorption and utilization by the body. Detailed Implementation

[0016] 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.

[0017] This invention provides an application of a coating premix in tamsulosin hydrochloride sustained-release tablets. The coating premix comprises, by weight, 40-60 parts of Eutrich RS100, 20-30 parts of Eutrich 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 in a mass ratio of 1:2:0.2.

[0018] Specifically, the solvent is 80 wt.% ethanol.

[0019] Specifically, the plasticizer is one or more of polyethylene glycol 6000, triethyl citrate, glycerin, or propylene glycol.

[0020] Specifically, the colorant is one or more of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, or carmine aluminum lake.

[0021] Specifically, the anti-adhesion agent is one or more of talc, glyceryl monostearate, or magnesium stearate.

[0022] Specifically, the average particle size of talc is 4-5 μm, and its whiteness is 94.

[0023] Specifically, polyethylene glycol 6000 has a viscosity of 5.5-9.0 mm. 2 / s, pH 6.

[0024] Specifically, the relative density of triethyl citrate is 1.1389.

[0025] The present invention also provides a tamsulosin hydrochloride sustained-release tablet, comprising a tamsulosin hydrochloride sustained-release tablet, wherein the surface of the tamsulosin hydrochloride sustained-release tablet is coated with a coating premix as described in any one of the above.

[0026] The coating premix for tamsulosin hydrochloride sustained-release tablets provided by the present invention, Eudragit RS100 and Eudragit RL100 are water-insoluble film-forming materials that can swell in water and are cationic polymers composed of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate; the molar ratio of these three in Eudragit RS100 is 1:2:0.1, while in Eudragit 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 content of quaternary ammonium salt groups in Eudragit RS100 is relatively low, with relatively small permeability and swelling, and the coating formed by it can effectively block the release of drugs; the content of quaternary ammonium salt groups in Eudragit RL100 is relatively high, with relatively large permeability and swelling, and it can be used in combination with Eudragit RS to regulate the drug release rate of the coating preparation; the drug is mainly released by diffusion through the hydrophilic pores formed by the quaternary ammonium salt groups in the coating; by adjusting Eudragit RL100 and Eudragit RS100, the change in the pore size of the release layer is achieved, thereby regulating the release rate of the drug in the chip; effectively achieving the disintegration and release of the drug after reaching the ileocecal part of the human body, and achieving the full absorption and utilization of the drug.

[0027] The sustained-release layer premix proposed by the present invention, Eudragit RL / RS is insoluble in water but can swell and form pores in the coating. The pore diameter of Eudragit RL is 1 - 5 μm, and that of Eudragit RS is 0.1 - 0.6 μm. By reasonable proportioning, the release rate of the drug can be effectively controlled.

[0028] Example 1 Preparation process of the coating premix for tamsulosin hydrochloride sustained-release tablets: By weight, 40 parts of Eudragit RS100, 20 parts of Eudragit RL100, 10 parts of plasticizer, 15 parts of colorant, and 15 parts of anti-adhesive are poured into a mixer and mixed and stirred at room temperature for 1 h, 500 parts of solvent are added, and then stirred for 30 min. The obtained mixture is dried at 35 °C for 5 h, sampled and inspected, and the moisture content is detected to be ≤8%. After passing the inspection, the mixture is ground and sieved to obtain the coating premix for tamsulosin hydrochloride sustained-release tablets; Among them, Eudragit RS100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate, and the mass ratio of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate is 1:2:0.1; Eudragit RL100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate, and the mass ratio of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate is 1:2:0.2.

[0029] The solvent in this example is 80 wt.% ethanol.

[0030] The plasticizer in this example is polyethylene glycol 6000.

[0031] The colorant in this example is titanium dioxide.

[0032] The anti-adhesive agent in this embodiment is talcum powder.

[0033] The average particle size of the talcum powder in this embodiment is 4 - 5 μm, and the whiteness is 94.

[0034] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5 - 9.0 mm 2 / s and a pH value of 6; The relative density of the triethyl citrate in this embodiment is 1.1389.

[0035] The coating premix for the tamsulosin hydrochloride sustained-release tablets is mixed with the tamsulosin hydrochloride sustained-release tablets at a mass ratio of 1:9, and the coating premix is coated on the outer surface of the tamsulosin hydrochloride sustained-release tablets to obtain the tamsulosin hydrochloride sustained-release tablets, and the release rate is shown in Table 1.

[0036] Example Two Preparation process of the coating premix for the tamsulosin hydrochloride sustained-release tablets: By weight, 60 parts of Eudragit RS100, 30 parts of Eudragit RL100, 15 parts of plasticizer, 20 parts of colorant, and 20 parts of anti-adhesive agent are poured into a mixer, mixed and stirred at room temperature for 1 h, 600 parts of solvent are added, and then stirred for 30 min. The obtained mixture is dried at 45 °C for 5 h, sampled and inspected, and the detected moisture is ≤ 8%. After passing the inspection, the mixture is ground and sieved to obtain the coating premix for the tamsulosin hydrochloride sustained-release tablets; Among them, Eudragit RS100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate, and the mass ratio of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate is 1:2:0.1; Eudragit RL100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate with a mass ratio of 1:2:0.2.

[0037] The solvent in this embodiment is 80 wt.% ethanol.

[0038] The plasticizer in this embodiment is triethyl citrate and glycerol, and the mass ratio of triethyl citrate and glycerol is 2:1.

[0039] The colorant in this embodiment is lemon yellow aluminum lake and sunset yellow aluminum lake, and the mass ratio of lemon yellow aluminum lake and sunset yellow aluminum lake is 1:1.

[0040] The anti-adhesive agent in this embodiment is glycerol monostearate.

[0041] The average particle size of the talcum powder in this embodiment is 4 - 5 μm, and the whiteness is 94.

[0042] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5 - 9.0 mm 2 / s and a pH value of 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0043] The coating premix for the tamsulosin hydrochloride sustained-release tablets is mixed with the tamsulosin hydrochloride sustained-release tablets at a mass ratio of 1:9, and the coating premix is coated on the outer surface of the tamsulosin hydrochloride sustained-release tablets to obtain the tamsulosin hydrochloride sustained-release tablets, and the release rate is shown in Table 1.

[0044] Example 3 Preparation process of the coating premix for the tamsulosin hydrochloride sustained-release tablets: By weight, 50 parts of Eudragit RS100, 25 parts of Eudragit RL100, 12 parts of plasticizer, 17 parts of colorant, and 17 parts of anti-adhesive are poured into a mixer, mixed and stirred at room temperature for 1 h, 550 parts of solvent are added, and then stirred for 30 min. The obtained mixture is dried at 40 °C for 5 h, sampled and inspected, and the detected moisture is ≤8%. After passing the inspection, the mixture is ground and sieved to obtain the coating premix for the tamsulosin hydrochloride sustained-release tablets; Among them, Eudragit RS100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate, and the mass ratio of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate is 1:2:0.1; Eudragit RL100 includes ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl chloride methacrylate with a mass ratio of 1:2:0.2.

[0045] The solvent in this embodiment is 80 wt.% ethanol.

[0046] The plasticizer in this embodiment is glycerol.

[0047] The colorant in this embodiment is sunset yellow aluminum lake.

[0048] The anti-adhesive in this embodiment is talc powder and magnesium stearate, and the mass ratio of talc powder and magnesium stearate is 1:1.

[0049] The average particle size of the talc powder in this embodiment is 4 - 5 μm, and the whiteness is 94.

[0050] The polyethylene glycol 6000 in this embodiment has a viscosity of 5.5 - 9.0 mm 2 / s and a pH value of 6; The relative density of triethyl citrate in this embodiment is 1.1389.

[0051] The coating premix for tamsulosin hydrochloride sustained-release tablets was mixed with tamsulosin hydrochloride sustained-release tablets at a mass ratio of 1:9. The coating premix was then coated onto the outer surface of the tamsulosin hydrochloride sustained-release tablets to obtain tamsulosin hydrochloride sustained-release tablets. The release rate is shown in Table 1.

[0052] Comparative Example 1 The only difference between this comparative example and the coating premix for tamsulosin hydrochloride sustained-release tablets in Example 1 is the absence of Eutectic RS100. The coating premix for tamsulosin hydrochloride sustained-release tablets was mixed with tamsulosin hydrochloride sustained-release tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the tamsulosin hydrochloride sustained-release tablets to obtain tamsulosin hydrochloride sustained-release tablets. The release rate is shown in Table 1.

[0053] Comparative Example 2 The only difference between this comparative example and the coating premix for tamsulosin hydrochloride sustained-release tablets in Example 1 is the absence of Eutrich RL100. The coating premix for tamsulosin hydrochloride sustained-release tablets was mixed with tamsulosin hydrochloride sustained-release tablets at a mass ratio of 1:9. The coating premix coated the outer surface of the tamsulosin hydrochloride sustained-release tablets to obtain tamsulosin hydrochloride sustained-release tablets. The release rate is shown in Table 1.

[0054] Comparative Example 3 The tamsulosin hydrochloride extended-release tablets in this comparative example were not treated with coating premix, and the release rate is shown in Table 1.

[0055] Table 1. Release rate of tamsulosin hydrochloride extended-release tablets

[0056] Compared to Example 1, Comparative Example 1 showed a 63% release rate in intestinal fluid after 7 hours, which was significantly lower than that of 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.

[0057] Compared to Example 1, Comparative Example 2 showed a 60% release rate in intestinal fluid after 7 hours, which was significantly lower than that in Example 1 due to the absence of Eutrich RL100. This demonstrates that the addition of Eutrich RL100 has a significant impact on the overall release rate.

[0058] Compared with Example 1, Comparative Example 3 showed that since the tamsulosin hydrochloride sustained-release tablets were not coated, the drug was partially released in the gastric juice and 50% was released in the intestinal juice after 7 hours. It can be seen that the coating premix proposed in this invention has a certain control effect on the drug release of tamsulosin hydrochloride sustained-release tablets.

[0059] 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 therein. Such 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 tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release tablets, characterized in that: The solvent is 80 wt.% ethanol.

3. The application of the coating premix according to claim 1 in tamsulosin hydrochloride sustained-release tablets, characterized in that: The plasticizer is one or more of polyethylene glycol 6000, triethyl citrate, glycerin, or propylene glycol.

4. The application of the coating premix according to claim 1 in tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release 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 tamsulosin hydrochloride sustained-release tablets, characterized in that: The relative density of triethyl citrate is 1.1389.

9. A tamsulosin hydrochloride sustained-release tablet, characterized in that: This includes tamsulosin hydrochloride extended-release tablets, wherein the surface of the tamsulosin hydrochloride extended-release tablets is coated with a coating premix as described in any one of claims 1-8.

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