Sustained-release coating as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medicines, in particular to a sustained-release coating as well as a preparation method and application thereof. The coating adopts a three-layer gradient structure design and comprises an inner layer coating, a middle layer coating and an outer layer coating, and the layers are compounded and matched through ethyl cellulose and hydroxypropyl methylcellulose with different molecular weights and are combined with talcum powder filling amount with gradient decreasing and a triethyl citrate plasticizer, so that accurate regulation and control of drug release are realized. Through hierarchical swelling-diffusion dynamic balance, burst release is inhibited, the inner layer has high talcum powder content to resist initial swelling stress, the outer layer has low filling amount to maintain hydrophobic continuity, interface defects are reduced in combination with high-temperature curing, and the release stability and long-term storage performance of drugs such as dihydroergoline mesylate are remarkably improved; the problems of sudden release, damp-heat sensitivity, impurity generation and the like of a traditional single-layer coating are solved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a sustained-release coating and a preparation method and application thereof. Background Art

[0002] Sustained-release formulation technology is a key research area in the field of drug delivery. Its core goal is to achieve controlled drug release in vivo through specific process design, thereby prolonging drug efficacy, reducing dosing frequency, and improving patient compliance. Traditional sustained-release coating technologies often use a single-layer polymer film (such as ethyl cellulose or acrylic resin) to coat the tablet core, controlling the drug release rate by adjusting the coating thickness or adding pore-forming agents. However, these approaches have significant drawbacks.

[0003] During the initial phase of media penetration, monolayer coatings can easily lead to a burst of drug release due to local swelling or rapid pore formation, affecting the stability of plasma drug concentrations. During storage, changes in the crystallinity of the polymer material or reorganization of the membrane structure induced by a humid and hot environment can easily lead to a shift in the release profile. Microscopic defects in the coating (such as microcracks and interfacial delamination) can accelerate drug-media contact, triggering degradation of the active ingredient or excipient compatibility issues.

[0004] Therefore, it is urgent to develop a new multi-layer sustained-release coating technology. Through the gradient design of material properties between layers and combined with process parameter optimization, the precise control of drug release curve can be achieved, while improving the long-term stability and impurity control capabilities of the preparation. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to propose a sustained-release coating and its preparation method and application, so as to develop a multi-layer sustained-release coating tablet preparation technology that can accurately control the drug release curve, improve storage stability and inhibit impurity generation.

[0006] Based on the above objectives, the present invention provides a sustained-release coating, comprising an inner coating, a middle coating and an outer coating.

[0007] Furthermore, the weight ratio of the inner coating, the middle coating and the outer coating is 0.8-1.2:1.3-1.7:1.8-2.2.

[0008] Furthermore, the raw materials in the inner coating layer are as follows by weight: 40-50 parts of ethyl cellulose N10, 50-60 parts of hydroxypropyl methylcellulose, 2-4 parts of plasticizer and 28-36 parts of talc.

[0009] Furthermore, the raw materials in the middle layer coating are as follows by weight: 60-70 parts of ethyl cellulose N22, 30-40 parts of hydroxypropyl methylcellulose, 5-7 parts of plasticizer and 14-18 parts of talc.

[0010] Furthermore, the raw materials in the outer coating are as follows by weight: 80-90 parts of ethyl cellulose N50, 10-20 parts of hydroxypropyl methylcellulose, 10-15 parts of plasticizer and 6-10 parts of talc.

[0011] Preferably, the talc powder is talc powder that has passed through an 800-1200 mesh sieve.

[0012] Preferably, the model of the hypromellose is K4M.

[0013] Preferably, the plasticizer is triethyl citrate.

[0014] Preferably, the sustained-release coating is heat-cured after wrapping the tablet core, and the heat-curing temperature is 53-57° C. and the time is 10-14 hours.

[0015] Furthermore, the preparation method of the sustained-release coating is as follows:

[0016] (1) Ethyl cellulose N10 and hydroxypropyl methylcellulose are added to a mixed solvent of anhydrous ethanol and purified water, stirred for 40-50 minutes, and then plasticizer and talc are added. The mixture is stirred for 25-35 minutes and filtered to obtain an inner coating solution.

[0017] (2) Ethyl cellulose N22 and hydroxypropyl methylcellulose are added to a mixed solvent of anhydrous ethanol and purified water, stirred for 40-50 minutes, and then plasticizer and talc are added. Stirring is continued for 25-35 minutes, and filtering is performed to obtain a middle layer coating solution;

[0018] (3) Ethyl cellulose N50 and hydroxypropyl methylcellulose are added to a mixed solvent of anhydrous ethanol and purified water, stirred for 40-50 minutes, and then plasticizer and talc are added. Stirring is continued for 25-35 minutes, and filtered to obtain an outer coating solution;

[0019] (4) placing the tablet core on a fluidized bed, spraying the inner coating liquid first, then the middle coating liquid, and finally the outer coating liquid to obtain a coated tablet;

[0020] (5) The coated tablet is thermally cured to obtain a sustained-release tablet containing a sustained-release coating.

[0021] Preferably, the stirring speed in step (1), step (2) and step (3) is 500-700 rpm and the stirring temperature is 30-40°C.

[0022] Preferably, the mesh size of the filter used in step (1), step (2) and step (3) is 150-250 meshes.

[0023] Preferably, in step (4), the air inlet temperature of the fluidized bed is 40-44°C, and the tablet cores are preheated to 32-38°C.

[0024] Preferably, the atomization pressure of the spraying in step (4) is 0.6-1 bar, and the rate is 8-12 mL / min.

[0025] Furthermore, the sustained-release coating is used to prepare dihydroergotamine mesylate sustained-release tablets.

[0026] Beneficial effects of the present invention:

[0027] This invention utilizes a gradient combination of ethyl cellulose of varying molecular weights to create a coating structure with a dynamic equilibrium of swelling and diffusion. The inner layer of low-molecular-weight polymer provides a dense initial barrier, effectively inhibiting rapid permeation of the medium; the middle layer of medium-molecular-weight polymer regulates the swelling pressure distribution, preventing interfacial stress concentration; and the outer layer of high-molecular-weight polymer forms a highly crystalline hydrophobic barrier, delaying late-stage burst release. The gradual swelling characteristics of the three-layer structure result in a steady, increasing kinetic trend in drug release.

[0028] This invention utilizes a design where the talc content gradually decreases from the inner layer to the outer layer. The high filler content in the inner layer reduces polymer segment migration through physical barrier, enhancing coating rigidity and resisting initial swelling stress. The low filler content in the outer layer maintains the integrity of the polymer continuous phase, forming a homogeneous hydrophobic network. This gradient distribution effectively balances the coating's permeability resistance and mechanical strength, reducing the formation of microcracks induced by moisture and heat during storage.

[0029] The present invention uses high-temperature curing to promote the rearrangement and crystallization of ethylcellulose molecular chains, forming a dense and thermally stable coating structure. High-temperature curing also reduces interfacial defects between coating layers and enhances interlayer compatibility, thereby suppressing release rate fluctuations caused by polymer chain relaxation during long-term storage.

[0030] The present invention effectively reduces internal stress in the coating film and reduces interfacial defects through the design of molecular weight gradients between layers. The gradient filling of talc optimizes thermal insulation efficiency and avoids denaturation of the original drug during curing. The synergistic effect of these two factors significantly improves the chemical stability of the product. DETAILED DESCRIPTION

[0031] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to specific embodiments.

[0032] Example 1:

[0033] (1) 40 g of ethyl cellulose N10 and 50 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 250 mL of anhydrous ethanol and 250 mL of purified water, stirred at 500 rpm for 40 min at 30°C, then 2 g of triethyl citrate and 28 g of talc (passed through an 800-mesh sieve) were added, and the mixture was stirred at 500 rpm for 25 min. The mixture was filtered through a 150-mesh filter to obtain an inner coating solution;

[0034] (2) 60 g of ethyl cellulose N22 and 30 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 350 mL of anhydrous ethanol and 150 mL of purified water, stirred at 500 rpm for 40 min at 30°C, and then 5 g of triethyl citrate and 14 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 500 rpm for 25 min and filtered through a 150 mesh filter to obtain a middle coating solution.

[0035] (3) 80 g of ethyl cellulose N50 and 10 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 450 mL of anhydrous ethanol and 50 mL of purified water, stirred at 500 rpm for 40 min at 30°C, and then 10 g of triethyl citrate and 6 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 500 rpm for 25 min and filtered through a 150 mesh filter to obtain an outer coating solution.

[0036] (4) Dihydroergoline mesylate raw material (particle size D90 of 14 μm) and microcrystalline cellulose PH-102 were wet granulated at a mass ratio of 1:3, and a 5 wt% polyvinylpyrrolidone K30 ethanol solution was used as a binder. The mixture was fluidized bed dried to a moisture content of 1.8%, and tablets were obtained with a diameter of 8.0 mm and a hardness of 8.5 kp.

[0037] (4) The inlet air temperature of the fluidized bed was set at 40°C. After the tablet cores were preheated to 32°C, the inner coating liquid was sprayed at a rate of 8 mL / min at an atomizing pressure of 0.6 bar. When the coating weight gain reached 0.8%, the middle coating liquid was sprayed at a rate of 8 mL / min at an atomizing pressure of 0.6 bar. When the coating weight gain reached 1.3%, the outer coating liquid was sprayed at a rate of 8 mL / min at an atomizing pressure of 0.6 bar. When the coating weight gain reached 1.8%, the coated tablets were obtained.

[0038] (5) The coated tablets were cured at 53° C. for 10 h to obtain dihydroergotamine mesylate sustained-release tablets containing a sustained-release coating.

[0039] Example 2:

[0040] (1) Add 45 g of ethyl cellulose N10 and 55 g of hydroxypropyl methylcellulose K4M to a mixed solvent of 300 mL of anhydrous ethanol and 300 mL of purified water, stir at 600 rpm for 45 min at 35°C, then add 3 g of triethyl citrate and 32 g of talc (passed through a 1000 mesh sieve), continue stirring at 600 rpm for 30 min, and filter through a 200 mesh filter to obtain an inner coating solution;

[0041] (2) 65 g of ethyl cellulose N22 and 35 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 400 mL of anhydrous ethanol and 200 mL of purified water, stirred at 600 rpm for 45 min at 35°C, and then 6 g of triethyl citrate and 16 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 600 rpm for 30 min and filtered through a 200 mesh filter to obtain a middle coating solution.

[0042] (3) 85 g of ethyl cellulose N50 and 15 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 500 mL of anhydrous ethanol and 100 mL of purified water, stirred at 600 rpm for 45 min at 35°C, and then 12 g of triethyl citrate and 8 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 600 rpm for 30 min and filtered through a 200 mesh filter to obtain an outer coating solution.

[0043] (4) The dihydroergotamine mesylate raw material (particle size D90: 14 μm) and microcrystalline cellulose PH-102 were wet granulated at a mass ratio of 1:3. A 5 wt% polyvinylpyrrolidone K30 ethanol solution was used as a binder. The mixture was fluidized bed dried to a moisture content of 1.8%, and tablets were obtained with a diameter of 8.0 mm and a hardness of 8.5 kp.

[0044] (4) The inlet air temperature of the fluidized bed was set at 42°C. After the tablet cores were preheated to 35°C, the inner coating liquid was sprayed at a rate of 10 mL / min at an atomizing pressure of 0.8 bar. When the coating weight gain reached 1%, the middle coating liquid was sprayed at a rate of 10 mL / min at an atomizing pressure of 0.8 bar. When the coating weight gain reached 1.5%, the outer coating liquid was sprayed at a rate of 10 mL / min at an atomizing pressure of 0.8 bar. When the coating weight gain reached 2%, the coated tablets were obtained.

[0045] (5) The coated tablets were cured at 55° C. for 12 h to obtain dihydroergotamine mesylate sustained-release tablets containing a sustained-release coating.

[0046] Example 3:

[0047] (1) 50 g of ethyl cellulose N10 and 60 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 350 mL of anhydrous ethanol and 350 mL of purified water, stirred at 700 rpm for 50 min at 40°C, then 4 g of triethyl citrate and 36 g of talc (passed through a 1200 mesh sieve) were added, and the mixture was stirred at 700 rpm for 35 min. The mixture was filtered through a 250 mesh filter to obtain an inner coating solution;

[0048] (2) 70 g of ethyl cellulose N22 and 40 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 450 mL of anhydrous ethanol and 250 mL of purified water, stirred at 700 rpm for 50 min at 40°C, and then 7 g of triethyl citrate and 18 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 700 rpm for 35 min and filtered through a 250 mesh filter to obtain a middle layer coating solution.

[0049] (3) 90 g of ethyl cellulose N50 and 20 g of hydroxypropyl methylcellulose K4M were added to a mixed solvent of 550 mL of anhydrous ethanol and 150 mL of purified water, stirred at 700 rpm for 50 min at 40°C, and then 15 g of triethyl citrate and 10 g of talc (passed through a 1000 mesh sieve) were added. The mixture was stirred at 700 rpm for 35 min and filtered through a 250 mesh filter to obtain an outer coating solution.

[0050] (4) The dihydroergotamine mesylate raw material (particle size D90: 14 μm) and microcrystalline cellulose PH-102 were wet granulated at a mass ratio of 1:3. A 5 wt% polyvinylpyrrolidone K30 ethanol solution was used as a binder. The mixture was fluidized bed dried to a moisture content of 1.8%, and tablets were obtained with a diameter of 8.0 mm and a hardness of 8.5 kp.

[0051] (4) The inlet air temperature of the fluidized bed was set at 44°C. After the tablet cores were preheated to 38°C, the inner coating liquid was sprayed at a rate of 12 mL / min at an atomizing pressure of 1 bar. When the coating weight gain reached 1.2%, the middle coating liquid was sprayed at a rate of 12 mL / min at an atomizing pressure of 1 bar. When the coating weight gain reached 1.7%, the outer coating liquid was sprayed at a rate of 12 mL / min at an atomizing pressure of 1 bar. When the coating weight gain reached 2.2%, the coated tablets were obtained.

[0052] (5) The coated tablets were cured at 57° C. for 14 h to obtain dihydroergotamine mesylate sustained-release tablets containing a sustained-release coating.

[0053] Comparative Example 1:

[0054] The difference between Comparative Example 1 and Example 1 is that the coating does not use the inner coating liquid, and the weight gain of the middle coating liquid is 2.5%;

[0055] Comparative Example 2:

[0056] The difference between Comparative Example 2 and Example 2 is that the coating does not use the middle coating liquid, and the weight gain of the outer coating liquid is 3.5%;

[0057] Comparative Example 3:

[0058] The difference between Comparative Example 3 and Example 2 is that: the coating does not use the outer coating liquid, and the weight gain of the middle coating liquid is 3.5%;

[0059] Comparative Example 4:

[0060] The difference between Comparative Example 4 and Example 2 is that the curing temperature of the coated tablets in step (5) is 40°C.

[0061] Comparative Example 5:

[0062] The difference between Comparative Example 5 and Example 2 is that only the outer coating liquid is used, and the weight gain of the outer coating liquid is 4.5%;

[0063] Comparative Example 6:

[0064] The difference between Comparative Example 6 and Example 2 is that the ethyl cellulose type in the inner, middle and outer coating solutions is N22;

[0065] Comparative Example 7:

[0066] The difference between Comparative Example 7 and Example 2 is that the amount of talc powder used in the inner, middle and outer coating solutions is 8 g.

[0067] Performance testing:

[0068] Release test: Take each sample and test it according to the release test method (Pharmacopoeia of the People's Republic of China 2015 edition Part IV 0931 Dissolution and Release Test Method 1), using the dissolution test method method 3 apparatus, with 500mL of hydrochloric acid solution (6→1000) as the release medium, the speed is 100 revolutions per minute, operate according to the law, after 2 hours, 6 hours, 10 hours and 12 hours, take 2mL of solution respectively, centrifuge (3000 revolutions per minute), take the supernatant as the test solution, and promptly add 2mL of solvent at the same temperature to the operating container. Separately, accurately weigh an appropriate amount of dihydroergoline methanesulfonate reference substance and dilute it with solvent to make a solution containing 10μg per 1mL as the reference substance solution. The determination was performed according to high-performance liquid chromatography (HPLC method 0512, Part IV, 2015 edition of the Pharmacopoeia of the People's Republic of China). Octadecylsilane bonded silica gel was used as the filler; the mobile phase was a 0.005 mol / L diammonium hydrogen phosphate solution-methanol (25:75) at a flow rate of 1.0 mL / min; the detection wavelength was 280 nm, and the number of theoretical plates, calculated based on the first main peak, should be no less than 2500. Accurately measure 50 μL each of the reference solution and the test solution, inject them into the liquid chromatograph, record the chromatogram, and calculate the release amount of each tablet at different times based on the total peak area using the external standard method. The results are shown in Table 1, and the calculation formula is as follows:

[0069]

[0070] Where K is the correction factor

[0071] Wr is the weight of the reference substance;

[0072] Ar is the peak area of the reference substance;

[0073] As is the peak area of the sample;

[0074] T is the content of the reference substance;

[0075] F is the water content of the reference substance.

[0076] Related substance test: According to the requirements of the Pharmacopoeia of the People's Republic of China (2015 edition, Part IV), the impurity content of the sample was analyzed by high performance liquid chromatography. The test conditions were the same as those for the release determination. The total impurity content was calculated. The results are shown in Table 1.

[0077] Stability: According to the requirements of the stability test of the 2015 edition of the Pharmacopoeia of the People's Republic of China, the accelerated test conditions were 40°C ± 2°C / 75% RH ± 5% for 6 months. The release rate and total impurity content were tested. The results are shown in Table 2.

[0078] Table 1 Release and related substances test results

[0079]

[0080] Table 2 Sustained release stability test results

[0081]

[0082]

[0083] Data Analysis:

[0084] The dihydroergotamine mesylate sustained-release tablets containing sustained-release coatings prepared in Examples 1-3 showed a low burst effect in the initial release stage, followed by a steady and increasing sustained-release trend, and the release curve in the accelerated stability test was highly consistent with the initial test results, while the increase in impurity content was small. It is speculated that the mechanism may be that the gradient design of ethyl cellulose types (N10 / N22 / N50) in the multi-layer coating system regulates the porosity and swelling properties of the coating film through molecular weight differences. The synergistic effect of the inner layer of low molecular weight ethyl cellulose (N10) and the middle and outer layers of high molecular weight ethyl cellulose (N22 / N50) may form a dense but permeability-controlled composite membrane structure, thereby slowing down the drug diffusion rate. In addition, the gradient addition of talc (32 g inner layer → 16 g middle layer → 8 g outer layer) may optimize the balance between the mechanical strength of the membrane and the drug release path by adjusting the viscosity of the coating liquid and the filling effect of the particles during the curing process. The higher curing temperature may promote the crystallization of the ethyl cellulose molecular chain and enhance the moisture and heat resistance of the coating film, thereby reducing the release rate fluctuation and impurity generation caused by the relaxation of the polymer chain during storage.

[0085] The initial release rate of Comparative Example 1 is significantly higher than that of Example 2, and the increase in impurities in the accelerated test is more obvious. This shows that the inner coating may reduce the rapid dissolution of the drug in the medium by providing an initial barrier effect. The combination of ethyl cellulose N10 (low molecular weight) and a high proportion of talc (32g) in the inner coating solution may form a dense bottom layer with less microporous structure, limiting the early diffusion of the drug; while Comparative Example 1, which lacks an inner layer, directly exposes the middle coating, and its lower talc content (16g) may lead to an increase in membrane porosity and accelerate medium penetration. In addition, the high proportion of talc in the inner coating may reduce the mobility of the ethyl cellulose molecular chain by physical filling, inhibiting the plastic deformation of the membrane structure during storage, thereby maintaining release stability.

[0086] The release curve of Comparative Example 2 shows hysteresis in the medium term (6-10h), and the impurity content rises in the accelerated test. It is speculated that the absence of the middle layer coating destroys the molecular weight transition gradient of ethyl cellulose, causing the outer layer high molecular weight N50 to directly cover the inner layer low molecular weight N10, which may form an interface defect due to the compatibility difference between the two levels. In the middle layer coating solution, ethyl cellulose N22 (middle molecular weight) may serve as a buffer layer to regulate the swelling rate difference between the inner and outer layers, avoiding the film rupture caused by stress concentration. In addition, the talc content (16g) in the middle layer coating is between the inner and outer layers, and it is possible to optimize the overall hydrophobicity of the coating film by gradient distribution, reduce the mutation of medium penetration, thereby maintaining linear release characteristics.

[0087] Comparative Example 3 showed a sudden release in the late release stage, and impurities increased significantly in the accelerated test. This shows that the ethyl cellulose N50 (high molecular weight) in the outer coating may maintain membrane integrity under the long-term action of the medium through high crystallinity and low swelling. The low talc content (8g) in the outer coating liquid may reduce the interference of inorganic particles on the polymer continuous phase, forming a more homogeneous hydrophobic barrier. However, Comparative Example 3 relies only on the middle layer coating, and its ethyl cellulose N22 has a low molecular weight. After long-term contact with the medium, the membrane porosity may increase due to excessive swelling, accelerating the late release of the drug. At the same time, the risk of degradation of the polymer chain in a hot and humid environment increases, leading to the generation of impurities.

[0088] Comparative Example 4 showed significant fluctuations in release rate and an increase in impurities during accelerated testing. It is speculated that the 55°C curing temperature may have enhanced the thermal stability of the coating by promoting rearrangement and crystallization of the ethylcellulose molecular chains. At higher temperatures, the insulating effect of talc may have reduced local thermal stress, resulting in a more uniform microstructure in the coating. However, the low-temperature curing of Comparative Example 4 may have resulted in insufficient stretching of the ethylcellulose molecular chains and insufficient crystallinity. In the accelerated test, the increased chain motion induced by moisture and heat led to plastic deformation of the film structure, altered release pathways, and increased polymer degradation side reactions.

[0089] The release curve of Comparative Example 5 shows an early burst release and a late excessively fast release, and the impurity content increases significantly. This shows that a single coating layer cannot regulate the release kinetics through the swelling-diffusion synergistic effect between layers. In a multilayer coating system, the inner dense membrane delays the initial release, the middle transition layer balances the swelling pressure, and the outer hydrophobic membrane inhibits the late burst release. The single-layer structure of Comparative Example 5 may quickly form penetrating channels after the medium penetrates, resulting in uncontrolled release. In addition, the high weight gain (4.5%) in the single-layer coating may generate internal stress due to the excessive thickness of the film, which is prone to cracking during solidification and accelerates the precipitation of impurities during storage.

[0090] The release curve of Comparative Example 6 shows an abnormal increase in the mid-term rate. It is speculated that the gradient design of the ethyl cellulose model regulates the swelling dynamics of the membrane through molecular weight differences. In Example 2, the inner layer N10 (low molecular weight) swells faster but has low mechanical strength, the middle layer N22 provides transitional support, and the outer layer N50 (high molecular weight) swells slowly but has strong permeability resistance. The uniform N22 coating of Comparative Example 6 may form a homogeneous swelling layer under the action of the medium due to a single swelling rate, resulting in a lack of gradient regulation of the drug diffusion rate. In addition, the low swelling property of the high molecular weight N50 in the outer layer may reduce the deep erosion of the coating membrane by the medium, thereby maintaining release stability in the accelerated test.

[0091] The release stability of Comparative Example 7 decreased significantly, and the impurity increase was obvious in the accelerated test. It is speculated that the gradient addition of talc (32g inner layer → 16g middle layer → 8g outer layer) optimizes the curing effect by regulating the thermal conductivity and mechanical strength of each layer of coating. The high talc content in the inner layer may enhance the thermal insulation, slow down the local overheating of ethyl cellulose during curing, and avoid excessive cross-linking of polymer chains; while the low talc content in the outer layer reduces the damage of the hydrophobic continuous phase by inorganic particles. The uniform low talc dosage of Comparative Example 7 may lead to insufficient thermal insulation of the inner layer, uneven crystallinity of ethyl cellulose during curing, defects in the membrane structure, and the moisture-heat-induced membrane reorganization in the accelerated test exacerbated the release fluctuation and impurity generation.

[0092] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Within the scope of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

Claims

1. A sustained-release coating, characterized in that: The invention comprises an inner coating, a middle coating and an outer coating; the weight ratio of the inner coating, the middle coating and the outer coating is 0.8-1.2:1.3-1.7:1.8-2.2; The raw materials in the inner coating are as follows by weight: 40-50 parts of ethyl cellulose N10, 50-60 parts of hypromellose, 2-4 parts of plasticizer and 28-36 parts of talc; The raw materials in the middle coating are as follows by weight: 60-70 parts of ethyl cellulose N22, 30-40 parts of hypromellose, 5-7 parts of plasticizer and 14-18 parts of talc; The raw materials in the outer coating are as follows by weight: 80-90 parts of ethyl cellulose N50, 10-20 parts of hypromellose, 10-15 parts of plasticizer and 6-10 parts of talc; The sustained-release coating is heat-cured after wrapping the tablet core, with the heat-curing temperature being 53-57° C. and the time being 10-14 hours.

2. The sustained-release coating according to claim 1, characterized in that The talcum powder is talcum powder that has passed through an 800-1200 mesh sieve.

3. The sustained-release coating according to claim 1, characterized in that The model of the hypromellose is K4M.

4. The sustained-release coating according to claim 1, characterized in that The plasticizer is triethyl citrate.

5. A method for preparing the sustained-release coating according to any one of claims 1 to 4, characterized in that: The following steps are involved: (1) Add ethyl cellulose N10 and hydroxypropyl methylcellulose to a mixed solvent of anhydrous ethanol and purified water, stir for 40-50 minutes, then add plasticizer and talc, continue stirring for 25-35 minutes, filter, and obtain the inner coating solution; (2) Add ethyl cellulose N22 and hydroxypropyl methylcellulose to a mixed solvent of anhydrous ethanol and purified water, stir for 40-50 minutes, then add plasticizer and talc, continue stirring for 25-35 minutes, filter, and obtain a middle layer coating solution; (3) Add ethyl cellulose N50 and hydroxypropyl methylcellulose to a mixed solvent of anhydrous ethanol and purified water, stir for 40-50 minutes, then add plasticizer and talc, continue stirring for 25-35 minutes, filter, and obtain an outer coating solution; (4) Place the tablet core on the fluidized bed, spray the inner coating liquid first, then spray the middle coating liquid, and finally spray the outer coating liquid to obtain a coated tablet; (5) The coated tablets are thermally cured to obtain sustained-release tablets containing a sustained-release coating.

6. The method for preparing a sustained-release coating according to claim 5, characterized in that: In the steps (1), (2) and (3), the stirring speed is 500-700 rpm and the stirring temperature is 30-40°C.

7. The method for preparing a sustained-release coating according to claim 5, characterized in that: The mesh size of the filter used in step (1), step (2) and step (3) is 150-250 mesh.

8. The method for preparing a sustained-release coating according to claim 5, characterized in that: In step (4), the air inlet temperature of the fluidized bed is 40-44°C, and the tablet core is preheated to 32-38°C.

9. The method for preparing a sustained-release coating according to claim 5, characterized in that: The atomization pressure of the spraying in step (4) is 0.6-1 bar, and the spraying rate is 8-12 mL / min.

10. A use of the sustained-release coating according to any one of claims 1 to 4, characterized in that: Used to prepare dihydroergotamine mesylate sustained-release tablets.

Images