Coating composition, method of manufacture and coating process for nifedipine sustained release tablets

Abstract

The application discloses a coating composition of nifedipine sustained-release tablets, a preparation method and a coating process. The composition comprises HPC-L, HPC-M, polydopamine, PVP K30 and hydrophilic nanosilica, and can improve the hydration coordination of the coating layer, the film stability and the sustained-release stability.

Description

Technical Field

[0001] This invention relates to the technical field of nifedipine sustained-release tablets, and in particular to a coating composition, preparation method, and coating process for nifedipine sustained-release tablets. Background Technology

[0002] Existing nifedipine sustained-release tablets mostly employ a hydrophilic gel matrix system to achieve slow drug release. To balance the initial release rate and the sustained release in the later stages, hydroxypropyl cellulose (HPC) of different viscosity grades is typically combined, for example, using low-viscosity HPC-L and high-viscosity HPC-M to construct a composite hydrophilic gel matrix. Low-viscosity HPC-L has rapid water absorption and wetting ability, promoting rapid media penetration, while high-viscosity HPC-M can form a high-strength gel barrier after hydration, thus slowing down the drug diffusion rate. However, the aforementioned dual-viscosity HPC compound system still has significant technical drawbacks in practical applications.

[0003] Specifically, due to significant differences in hydration rates and gel-formation behavior between HPC-L and HPC-M, HPC-L preferentially and rapidly absorbs water and swells upon contact with the dissolution medium, while HPC-M, due to its higher viscosity, forms a gel layer relatively slowly. This results in the formation of unstable gel regions with relatively loose structures and insufficient mechanical strength in the outer layer of the formulation during the initial release phase. Before HPC-M establishes a complete blocking network, the drug tends to diffuse and release rapidly along locally loose channels, leading to a significant initial burst release phenomenon. This also causes problems such as large fluctuations in the initial release curve and insufficient stability of sustained-release behavior. Summary of the Invention

[0004] This application provides a coating composition for nifedipine sustained-release tablets, comprising, by weight: Hydroxypropyl cellulose (HPC-L) 20–60 parts; Hydroxypropyl cellulose (HPC-M) 10–50 parts; Polydopamine 0.1–15 parts; Polyvinylpyrrolidone (PVP) K30: 1-20 parts; Hydrophilic nano-silica Aerosil 200 Pharma 0.1-10 parts.

[0005] It should be noted that the amount of hydroxypropyl cellulose (HPC-L) used is 20–60 parts, mainly used to improve the initial wettability and media penetration of the coating layer; the amount of hydroxypropyl cellulose (HPC-M) used is 10–50 parts, mainly used to form a gel blocking layer with a certain strength to maintain the sustained release of the drug in the middle and late stages; the amount of polydopamine used is 0.1–15 parts, as an interface coordinating and skeleton bridging component, used to improve the hydration coordination and structural stability of the HPC-L and HPC-M composite system; the amount of polyvinylpyrrolidone (PVP K30) used is 1–20 parts, used to improve the film-forming continuity and adhesion of the coating composition; and the amount of hydrophilic nano-silica Aerosil 200 Pharma used is 0.1–10 parts, used to adjust the dispersion stability and rheological properties of the coating slurry and improve the uniformity of the microstructure of the coating layer. The above components work synergistically to give the coating layer the characteristics of coordinated initial hydration, gelation inhibition in the middle and late stages, continuous film formation, and uniform release channels, thereby improving the release stability of nifedipine sustained-release tablets.

[0006] In a preferred embodiment of a coating composition for nifedipine sustained-release tablets, the weight ratio of hydroxypropyl cellulose HPC-L to hydroxypropyl cellulose HPC-M is 1:(0.3-2); the total weight ratio of polydopamine to hydroxypropyl cellulose HPC-L and hydroxypropyl cellulose HPC-M is (0.005-0.25):1.

[0007] It should be noted that this ratio is limited to coordinate the rapid wetting effect of HPC-L, the continuous gelation-blocking effect of HPC-M, and the interfacial stabilizing effect of polydopamine, so that the composite coating system can avoid rapid hydration and burst release in the early stage of release and maintain a stable gel barrier in the later stage of release.

[0008] In a preferred embodiment of a coating composition for nifedipine sustained-release tablets, the hydrophilic nano-silica Aerosil 200 Pharma has an average particle size of 5–50 nm.

[0009] It should be noted that this average particle size range is beneficial for the uniform dispersion of hydrophilic nano-silica in the HPC composite framework, and improves the anti-settling properties, rheological stability, and microporous structure uniformity of the coating slurry.

[0010] In addition, this application provides a method for preparing a coating composition for nifedipine sustained-release tablets, comprising the following steps: S1. Polydopamine, hydroxypropyl cellulose HPC-L, and hydroxypropyl cellulose HPC-M are added to a mixing device for premixing to obtain a composite gel skeleton premix. S2. Polyvinylpyrrolidone (PVP) K30 and hydrophilic nano-silica Aerosil 200 Pharma are added to the composite gel skeleton premix obtained in step S1 and mixed and dispersed to obtain a coating composition.

[0011] It should be noted that in step S1, polydopamine is first premixed with HPC-L and HPC-M, allowing polydopamine to preferentially distribute between the low-viscosity HPC-L and the high-viscosity HPC-M. This plays a role in interface coordination, skeleton bridging, and hydration behavior regulation, thereby mitigating the mismatch between the rapid hydration of HPC-L and the slow gelation of HPC-M, forming a relatively stable composite gel skeleton premix. In step S2, PVP K30 and hydrophilic nano-silica Aerosil 200Pharma are added. PVP K30 improves the film-forming continuity and component compatibility of the system, while hydrophilic nano-silica improves the dispersion stability, rheological properties, and microstructure uniformity of the coating layer. As a result, the coating composition simultaneously possesses a stable gel skeleton, good film-forming properties, and uniform release channels. This process sequence is an important innovation that distinguishes it from the conventional simple mixing of coating excipients.

[0012] In a preferred embodiment of a method for preparing a coating composition for nifedipine sustained-release tablets, the premixing speed in step S1 is 200–1500 rpm and the mixing time is 5–60 min.

[0013] It should be noted that the premixing speed and mixing time range are used to ensure that polydopamine is fully and uniformly distributed between HPC-L and HPC-M, to avoid insufficient mixing leading to inadequate interfacial coordination, and to avoid excessive shearing causing powder agglomeration, structural damage, or decreased stability of subsequent coating slurry.

[0014] In a preferred embodiment of a method for preparing a coating composition for nifedipine sustained-release tablets, in step S1, polydopamine is pre-contaminated and mixed with hydroxypropyl cellulose HPC-M, and then mixed with hydroxypropyl cellulose HPC-L.

[0015] It should be noted that the invention of this step lies in the sequential premixing method of first contacting HPC-M with polydopamine and then introducing HPC-L, which preferentially improves the interfacial state and dispersion state of high-viscosity hydroxypropyl cellulose HPC-M in the composite skeleton. Since HPC-M is a key component for the later formation of a high-strength gel barrier layer, but its hydration rate is relatively slow, in the conventional direct mixing system of HPC-L / HPC-M, there is a time difference in which HPC-L absorbs water rapidly first and HPC-M has not yet fully gelled, resulting in a loose gel layer, uneven drug diffusion channels, and increased risk of burst release in the early stage of release. This application involves first contacting and mixing polydopamine with HPC-M. The adhesive properties, hydrogen bonding, and interfacial association of polydopamine can be used to pre-disperse and modulate the interface of HPC-M, making it easier for HPC-M to form a continuous and stable composite gel framework when it is subsequently mixed with HPC-L. This mitigates the mismatch between the rapid hydration of HPC-L and the slow gelation of HPC-M, and improves the coordination of the coating layer hydration process, the integrity of the gel barrier, and the stability of the sustained-release curve.

[0016] This application provides a coating preparation process for nifedipine sustained-release tablets, including the following steps: P1. Provides nifedipine sustained-release tablet cores; P2. The coating composition according to any one of claims 1 to 3 is formulated into a coating slurry; P3. Spray the coating paste onto the surface of the tablet core; P4. The coated tablet cores are dried and cured to obtain nifedipine sustained-release tablets.

[0017] It should be noted that the invention of this coating preparation process lies in further transforming the aforementioned composite coating composition into a stable sustained-release coating layer on the surface of the nifedipine sustained-release tablet core. By first preparing the coating composition into a coating slurry, then spraying it onto the surface of the tablet core and drying and curing it, HPC-L, HPC-M, polydopamine, PVP K30 and hydrophilic nano silica form a continuous, uniform and structurally stable composite gel coating layer. This enables coordinated hydration, stable gel formation and continuous release inhibition of the coating layer during drug release, demonstrating the synergistic effect between the formulation system and the coating molding process.

[0018] As a preferred technical solution for the coating preparation process of nifedipine sustained-release tablets, the coating is carried out by a multi-spray gun synchronous spraying method in step P3; during the spraying process, the tablet core temperature is controlled at 35-50℃, the inlet air temperature is 50-65℃, and the outlet air temperature is 40-55℃.

[0019] It should be noted that by using multiple spray guns to spray simultaneously and coordinating the control of the core temperature, inlet air temperature and outlet air temperature, the uniformity of coating slurry spraying on the core surface and the consistency of drying are improved, avoiding local over-wetting, over-drying, film cracking or uneven thickness, thereby ensuring the stability of the slow-release coating layer structure.

[0020] As a preferred technical solution for the coating preparation process of nifedipine sustained-release tablets, the drying and curing treatment in step P4 includes a low-temperature pre-curing stage and a heating drying stage; the temperature of the low-temperature pre-curing stage is 35-45℃ and the time is 10-60 min; the temperature of the heating drying stage is 45-70℃ and the time is 20-120 min.

[0021] It should be noted that claim 10 uses a staged curing method of low-temperature pre-curing and high-temperature drying to allow the coating layer to first complete the initial film formation and structural homogenization, and then further dry to enhance the film strength, thereby avoiding premature surface densification, uneven internal moisture migration, or unstable composite gel skeleton structure caused by rapid high-temperature drying.

[0022] The beneficial effects of this invention are as follows: By constructing a composite gel sustained-release framework using HPC-L and HPC-M, the coating layer possesses both initial wetting and penetration capabilities and mid-to-late-stage gelation blocking capabilities; by first contacting HPC-M with polydopamine and then mixing it with HPC-L, the hydration coordination between hydroxypropyl celluloses of different viscosities can be improved, reducing the risk of initial burst release; PVP K30 enhances the film-forming continuity and adhesion stability of the coating layer; and hydrophilic nano-silica improves the dispersion stability of the coating slurry and the uniformity of the film microstructure. Therefore, the resulting nifedipine sustained-release tablet coating layer exhibits a lower initial burst release rate, a lower erosion rate, better slurry anti-settling properties, and more stable in vitro release behavior, thereby improving the stability of the sustained-release tablet release curve and batch consistency. Attached Figure Description

[0023] Figure 1 The FTIR simulation comparison spectra are of the sequential premix of Example 1 and the single mixture of Control Example 4.

[0024] Figure 2 The in vitro cumulative release rate comparison curves are for Examples 1-4 and Control Examples 1-6. Detailed Implementation

[0025] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0026] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0027] Secondly, the term "an embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places throughout this specification does not necessarily refer to the same embodiment, nor is it a single embodiment or an embodiment selectively excluded from other embodiments.

[0028] Example 1

[0029] This embodiment provides a coating composition, preparation method, and coating process for nifedipine sustained-release tablets. The coating composition, by weight, comprises: 20 parts of hydroxypropyl cellulose (HPC-L), 10 parts of hydroxypropyl cellulose (HPC-M), 0.1 parts of polydopamine, 1 part of polyvinylpyrrolidone (PVP K30), and 0.1 parts of hydrophilic nano-silica Aerosil 200 Pharma; wherein the average particle size of the hydrophilic nano-silica Aerosil 200 Pharma is 5 nm.

[0030] The preparation method of the coating composition includes the following technical steps: Step S1. First, add polydopamine and hydroxypropyl cellulose HPC-M to a high-speed mixer and premix at 200 rpm for 2 min, so that polydopamine first contacts HPC-M and is distributed on the surface or between particles of HPC-M; then add hydroxypropyl cellulose HPC-L and continue mixing at 200 rpm for 3 min, for a total premixing time of 5 min, to obtain the composite gel skeleton premix.

[0031] Step S2. Add polyvinylpyrrolidone (PVP K30) and hydrophilic nano-silica Aerosil 200 Pharma to the composite gel skeleton premix obtained in step S1, and mix and disperse at 300 rpm for 10 min to ensure that PVP K30 and hydrophilic nano-silica are uniformly incorporated into the composite gel skeleton premix, thereby obtaining the coating composition.

[0032] The coating process for nifedipine sustained-release tablets includes the following technical steps: Step P1. First, install, debug, and test run the coating machine without load. After 5 minutes of no-load test run, confirm that the equipment is running normally. Then, verify the product name, specifications, batch number, and quantity of the nifedipine sustained-release tablet cores. Use an electronic scale to verify the weight of each barrel. After confirming that it matches the barrel label, use the lifting feeder to put the tablet cores into the coating machine.

[0033] Step P2. Add the above coating composition to purified water and disperse it under stirring to prepare a coating slurry. Stir until the slurry is uniform and there is no obvious agglomeration before use.

[0034] Step P3. First, set the main unit speed of the coating machine to 6 rpm and the peristaltic pump flow rate to 160 ml / min. Start the multi-spray gun synchronous spraying system and begin coating after confirming that the slurry is sprayed out normally. After spraying for 5 minutes, increase the main unit speed to 7 rpm and the peristaltic pump flow rate to 180 ml / min. After spraying for 10 minutes, increase the main unit speed to 8 rpm and the peristaltic pump flow rate to 300 ml / min. After spraying for 15 minutes, increase the main unit speed to 9 rpm and maintain the peristaltic pump flow rate at 300 ml / min. After spraying for 20 minutes, increase the main unit speed to 10 rpm and maintain the peristaltic pump flow rate at 300 ml / min. During the spraying process, use the multi-spray gun synchronous spraying method for coating, and control the core temperature to 35℃, the inlet air temperature to 50℃, and the outlet air temperature to 40℃. At the same time, monitor the core temperature, humidity, air volume, and negative pressure inside the coating pan.

[0035] Step P4. After spraying, the tablet core is dried and cured. First, it is pre-cured at a low temperature of 35℃ for 10 minutes to allow the coating layer to initially form a film and complete the structural stabilization. Then, the temperature is raised to 45℃ and dried for 20 minutes to obtain nifedipine sustained-release tablets. After spraying for 30 minutes, the tablet surface condition is observed every 10 minutes. When the tablet surface is dry, the film-coated tablet is undamaged, the surface is smooth and clean, the color is uniform, and the edges are neat, the spraying is stopped. After drying, the main machine speed is adjusted to 1-2 rpm for tablet air drying. After cooling to a core temperature of about 26℃, the discharge device is installed and the tablets are automatically discharged at 6 rpm.

[0036] Example 2

[0037] This embodiment provides a coating composition, preparation method, and coating process for nifedipine sustained-release tablets. The coating composition comprises: 50 parts hydroxypropyl cellulose (HPC-L), 15 parts hydroxypropyl cellulose (HPC-M), 0.325 parts polydopamine, 8 parts polyvinylpyrrolidone (PVP K30), and 3 parts hydrophilic nano-silica Aerosil 200 Pharma. The weight ratio of HPC-L to HPC-M is 1:0.3, the weight ratio of polydopamine to the total weight of HPC-L and HPC-M is 0.005:1, and the average particle size of the hydrophilic nano-silica Aerosil 200 Pharma is 10 nm.

[0038] The preparation method of the coating composition includes the following technical steps: Step S1: First, add polydopamine and hydroxypropyl cellulose HPC-M into a mixing device and mix at 500 rpm for 10 min to allow polydopamine to preferentially contact the high-viscosity HPC-M; then add hydroxypropyl cellulose HPC-L and continue mixing at 500 rpm for 10 min. The total premixing time is 20 min to obtain the composite gel skeleton premix.

[0039] Step S2: Add polyvinylpyrrolidone (PVP K30) and hydrophilic nano-silica Aerosil 200 Pharma to the composite gel skeleton premix obtained in step S1. Mix and disperse at 500 rpm for 15 min to improve the film-forming continuity of the system with PVP K30, and at the same time to make the hydrophilic nano-silica uniformly distributed in the composite gel skeleton premix to obtain the coating composition.

[0040] The coating process for nifedipine sustained-release tablets includes the following technical steps: Step P1: After the coating machine is installed and debugged, run it under no-load for 5 minutes to confirm that the main unit, spray gun, peristaltic pump, air intake system, air exhaust system and negative pressure monitoring system are operating normally; check the nifedipine sustained-release tablet cores, verify the product name, specifications, batch number and quantity, and weigh each barrel to confirm that there are no errors, and then put the tablet cores into the coating machine through the lifting feeder.

[0041] Step P2: Add the coating composition obtained in this embodiment to purified water to prepare a uniform coating slurry. Stir continuously during the preparation process to fully disperse the HPC composite framework, PVP K30 and hydrophilic nano silica.

[0042] Step P3: The prepared coating slurry is simultaneously sprayed onto the surface of the film core using multiple spray guns. At the start of spraying, the main unit speed is 6 rpm, the peristaltic pump flow rate is 160 ml / min, and the spraying temperature is set to 50℃. After confirming that the slurry is sprayed out, coating begins. In the initial 20 minutes of coating, the main unit speed and peristaltic pump flow rate are gradually increased. Specifically, after 5 minutes of spraying, the main unit speed is increased to 7 rpm and the peristaltic pump flow rate is increased to 180 ml / min; after 10 minutes of spraying, the main unit speed is increased to 8 rpm and the peristaltic pump flow rate is increased to 300 ml / min; after 15 minutes of spraying, the main unit speed is increased to 9 rpm; and after 20 minutes of spraying, the main unit speed is increased to 10 rpm while the peristaltic pump flow rate is maintained at 300 ml / min. During the spraying process, the film core temperature is controlled at 40℃, the inlet air temperature at 55℃, and the outlet air temperature at 45℃, and the temperature, humidity, air volume, and negative pressure are monitored in real time.

[0043] Step P4 involves staged drying and curing of the coated tablet cores. First, a low-temperature pre-curing process is performed at 38℃ for 25 minutes to form a continuous initial film layer on the tablet core surface. Then, the temperature is increased to 55℃ for 50 minutes to further solidify the coating layer into a film, yielding nifedipine sustained-release tablets. After 30 minutes of spraying, the tablet surface is observed every 10 minutes. Spraying is stopped when the tablet surface is dry, the film coating is intact, the surface is smooth and clean, the color is uniform, and the edges are neat. The main machine speed is then reduced to 1-2 rpm for tablet drying. The tablets are automatically discharged after the core temperature drops to 26℃.

[0044] Example 3

[0045] This embodiment provides a coating composition, preparation method, and coating process for nifedipine sustained-release tablets. The coating composition, by weight, comprises: 20 parts of hydroxypropyl cellulose (HPC-L), 40 parts of hydroxypropyl cellulose (HPC-M), 15 parts of polydopamine, 15 parts of polyvinylpyrrolidone (PVP K30), and 8 parts of hydrophilic nano-silica Aerosil 200 Pharma. The weight ratio of HPC-L to HPC-M is 1:2, the weight ratio of polydopamine to the total weight of HPC-L and HPC-M is 0.25:1, and the average particle size of the hydrophilic nano-silica Aerosil 200 Pharma is 30 nm.

[0046] The preparation method of the coating composition includes the following technical steps: Step S1: First, add 15 parts of polydopamine and 40 parts of hydroxypropyl cellulose (HPC-M) to a mixing device and premix at 1000 rpm for 20 min to ensure that the polydopamine is fully contacted and distributed in the HPC-M. Then add 20 parts of hydroxypropyl cellulose (HPC-L) and continue premixing at 1000 rpm for 20 min, for a total premixing time of 40 min, to obtain a composite gel skeleton premix. Step S2: Add 15 parts of polyvinylpyrrolidone (PVP K30) and 8 parts of hydrophilic nano-silica (Aerosil 200 Pharma) with an average particle size of 30 nm to the composite gel skeleton premix. Mix and disperse at 800 rpm for 20 min to ensure that the PVP K30 is fully mixed with the composite gel skeleton and that the hydrophilic nano-silica is evenly distributed, to obtain a coating composition.

[0047] The coating process for nifedipine sustained-release tablets includes the following technical steps: Step P1: Install, debug, and run the coating machine under no-load for 5 minutes to confirm normal operation. Then, recheck the nifedipine sustained-release tablet cores, including verifying the product name, specifications, batch number, and quantity, and weigh each batch. After verification, use a lifting feeder to feed the tablet cores into the coating machine. Step P2: Add the coating composition obtained in Example 3 to purified water and prepare a coating slurry under continuous stirring until the polymer components are completely wetted, the nano-silica is uniformly dispersed, and the slurry is stable. Step P3: The coating slurry is simultaneously sprayed onto the surface of the film core using multiple spray guns, with a one-gun-one-pump method to control the consistency of the slurry flow. At the start of spraying, the main unit speed is set to 6 rpm, the peristaltic pump flow rate is set to 160 ml / min, and the spraying temperature is set to 50℃. After confirming that the slurry is sprayed out, the coating begins. During the initial 20 minutes of coating, the speed and flow rate are gradually increased. After 5 minutes of spraying, the speed is adjusted to 7 rpm and 180 ml / min, after 10 minutes, the speed is adjusted to 8 rpm and 300 ml / min, after 15 minutes, the speed is adjusted to 9 rpm and 300 ml / min, and after 20 minutes, the speed is adjusted to 10 rpm and 300 ml / min. During the spraying process, the film core temperature is controlled at 45℃, the inlet air temperature at 60℃, and the outlet air temperature at 50℃, and the film core temperature, humidity, air volume, and negative pressure are monitored in real time. Step P4: After spraying, drying and curing are performed. First, low-temperature pre-curing is carried out at 42℃ for 45 minutes to allow the composite coating layer to form a preliminary film on the tablet core surface and homogenize the internal structure. Then, the temperature is raised to 60℃ for 90 minutes to further densify the film layer and improve its mechanical stability, resulting in nifedipine sustained-release tablets. After spraying for 30 minutes, the tablet surface is observed every 10 minutes. Spraying is stopped once it is confirmed that the tablet surface is dry, the film-coated tablets are undamaged, flat and smooth, the color is uniform, and the edges are neat. Then, the coating machine pot door is opened, and the main machine speed is set to 1-2 rpm for cooling. After cooling to a tablet core temperature of about 26℃, the tablets are automatically discharged using a discharge device, and the pot wall is automatically cleaned after discharge.

[0048] Example 4

[0049] This embodiment provides a coating composition, preparation method, and coating process for nifedipine sustained-release tablets. The coating composition, by weight, comprises: 60 parts of hydroxypropyl cellulose HPC-L, 50 parts of hydroxypropyl cellulose HPC-M, 15 parts of polydopamine, 20 parts of polyvinylpyrrolidone PVP K30, and 10 parts of hydrophilic nano-silica Aerosil 200 Pharma; wherein the average particle size of the hydrophilic nano-silica Aerosil 200 Pharma is 50 nm.

[0050] The preparation method of the coating composition includes the following technical steps: Step S1: First, polydopamine and hydroxypropyl cellulose (HPC-M) are added to a mixing device and mixed at 1500 rpm for 30 min to allow polydopamine to preferentially contact and mix with HPC-M. Then, hydroxypropyl cellulose (HPC-L) is added, and mixing continues at 1500 rpm for 30 min, for a total premixing time of 60 min, to obtain a composite gel framework premix. Step S2: Polyvinylpyrrolidone (PVP K30) and hydrophilic nano-silica (Aerosil 200 Pharma) with an average particle size of 50 nm are added to the composite gel framework premix obtained in Step S1. The mixture is mixed and dispersed at 1000 rpm for 30 min to ensure that PVP K30 is fully distributed in the HPC composite framework and that the hydrophilic nano-silica is uniformly dispersed, to obtain a coating composition.

[0051] The coating process for nifedipine sustained-release tablets includes the following technical steps: Step P1: Before coating, install, debug, and test-run the coating machine. After 5 minutes of no-load operation, confirm that the equipment is running normally. Then, check the nifedipine sustained-release tablet cores, verifying the product name, specifications, batch number, and quantity. Weigh each container using an electronic scale to confirm that the weight matches the label. Then, feed the tablet cores into the coating machine using a lifting feeder. Step P2: Add the coating composition obtained in this embodiment to purified water to prepare a coating slurry. Stir until the slurry is uniform and stable before use. Step P3: The coating slurry is simultaneously sprayed onto the surface of the film core using multiple spray guns. At the start of spraying, the main unit speed is set to 6 rpm, the peristaltic pump flow rate is set to 160 ml / min, and the spraying temperature is set to 50℃. After confirming that the slurry is sprayed out, coating begins. After 5 minutes of spraying, the main unit speed is increased to 7 rpm and the peristaltic pump flow rate is increased to 180 ml / min. After 10 minutes of spraying, the main unit speed is increased to 8 rpm and the peristaltic pump flow rate is increased to 300 ml / min. After 15 minutes of spraying, the main unit speed is increased to 9 rpm and the peristaltic pump flow rate is maintained at 300 ml / min. After 20 minutes of spraying, the main unit speed is increased to 10 rpm and the peristaltic pump flow rate is maintained at 300 ml / min. During the spraying process, the film core temperature is controlled at 50℃, the inlet air temperature is 65℃, and the outlet air temperature is 55℃. The film core temperature, humidity, air volume, and negative pressure are monitored in real time to ensure uniform spraying and film stability. Step P4 involves drying and curing the coated tablet core. First, pre-curing at 45℃ for 60 minutes allows the coating layer to form a preliminary film and homogenize its structure. Then, the temperature is raised to 70℃ for 120 minutes to fully dry and cure the coating layer, resulting in nifedipine sustained-release tablets. After 30 minutes of spraying, the tablet surface is observed every 10 minutes. Spraying is stopped when the surface is dry, the film-coated tablet is undamaged, smooth, evenly colored, and has neat edges. After drying, the main unit speed is set to 1–2 rpm for cooling, allowing the tablets to cool for 0.5–1 hour. Once the tablet core temperature drops to 26℃, the discharge device is installed, and the main unit speed is set to 6 rpm for automatic discharge.

[0052] Compare with Example 1 The difference between this comparative example and Example 1 is that polydopamine is not added to the coating composition. Correspondingly, in step S1, only hydroxypropyl cellulose HPC-M and hydroxypropyl cellulose HPC-L are premixed. Other components and process parameters are the same as in Example 1.

[0053] Compare with Example 2 The difference between this comparative example and Example 1 is that hydroxypropyl cellulose HPC-M is not added to the coating composition, and 10 parts of hydroxypropyl cellulose HPC-M in Example 1 are replaced with an equal amount of hydroxypropyl cellulose HPC-L, that is, the total amount of hydroxypropyl cellulose HPC-L in the coating composition is 30 parts. Other components and process parameters are the same as in Example 1.

[0054] Compare with Example 3 The difference between this comparative example and Example 1 is that hydroxypropyl cellulose HPC-L is not added to the coating composition, and 20 parts of hydroxypropyl cellulose HPC-L in Example 1 are replaced with an equal amount of hydroxypropyl cellulose HPC-M, that is, the total amount of hydroxypropyl cellulose HPC-M in the coating composition is 30 parts. Other components and process parameters are the same as in Example 1.

[0055] Compare with Example 4 The difference between this comparative example and Example 1 is that in step S1, instead of the sequential premixing method of "polydopamine first contacting HPC-M and then adding HPC-L", polydopamine, hydroxypropyl cellulose HPC-L and hydroxypropyl cellulose HPC-M are added to a high-speed mixer at the same time and mixed at 200 rpm for 5 min to obtain a composite gel skeleton premix; other components and process parameters are the same as in Example 1.

[0056] Compare with Example 5 The difference between this comparative example and Example 1 is that polyvinylpyrrolidone (PVPK30) is not added to the coating composition, while other components and process parameters are the same as in Example 1.

[0057] Compare with Example 6 The difference between this comparative example and Example 1 is that hydrophilic nano-silica Aerosil 200 Pharma is not added to the coating composition, while other components and process parameters are the same as in Example 1.

[0058] Performance testing methods 1. In vitro cumulative release rate: Take nifedipine sustained-release tablets obtained in Examples 1-4 and Control Examples 1-6, 6 tablets in each group, and test them using the paddle dissolution test. The release medium is 900 mL phosphate buffer, the temperature is controlled at 37±0.5℃, and the rotation speed is 75 rpm. Take 5 mL samples at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h respectively, and immediately add an equal volume of fresh release medium at the same temperature. After filtering the samples through a 0.45 μm filter membrane, the nifedipine content is determined by HPLC, the cumulative release percentage at each time point is calculated, and the in vitro cumulative release curve is plotted.

[0059] 2. Initial burst release rate: The initial burst release rate was calculated using data obtained from in vitro cumulative release rate testing. The cumulative release percentage at 1 hour was used as the initial burst release rate. The average value of 6 samples in each group was taken as the final result, and the standard deviation was calculated. The ability of the coating layer to inhibit the initial rapid release was evaluated by comparing the 1-hour release percentage of Examples 1-4 with that of Control Examples 1, 2, and 4. The lower the 1-hour release percentage and the smaller the intra-group deviation, the better the initial burst release control effect.

[0060] 3. Water absorption, swelling and erosion properties of the coating layer: Take the coated tablets obtained from Examples 1-4 and Comparative Examples 1-6, 6 tablets in each group, accurately weigh the initial mass W0, and place them in phosphate buffer at 37±0.5℃. Take them out at 0.5h, 1h, 2h and 4h, gently absorb the free water on the surface with filter paper and weigh the wet mass Wt. Calculate the water absorption swelling rate according to "water absorption swelling rate = (Wt - W0) / W0 × 100%"; then dry the same sample at 45℃ to constant weight, weigh the dried mass Wd, and calculate the erosion rate according to "erosion rate = (W0 - Wd) / W0 × 100%".

[0061] 4. Settling stability of coating slurry: The coating compositions of Examples 1-4 and Comparative Examples 1-6 were prepared into coating slurries with the same solid content. 50 mL of each group was placed in a stoppered graduated cylinder and allowed to stand at 25°C for 24 h. Whether stratification, settling or obvious agglomeration occurred was recorded. After standing, 10 mL of the upper layer and 10 mL of the lower layer of slurry were taken, dried to constant weight, and the solid content was measured. The solid content was calculated according to "solid content deviation = |lower layer solid content - upper layer solid content| / average solid content × 100%". The smaller the solid content deviation, the better the dispersion stability and anti-settling performance of the slurry.

[0062] Table 1. Initial burst release rate test results of Examples 1-4 and Control Examples 1-6

[0063] Table 2. Test results of water absorption swelling rate of the coating layer in Examples 1-4 and Comparative Examples 1-6

[0064] Table 3. Test results of coating erosion rate of Examples 1-4 and Comparative Examples 1-6

[0065] Table 4. Settling stability test results of coating slurries in Examples 1-4 and Control Examples 1-6

[0066] The FTIR simulation spectra show that the infrared absorption peak types of the single-use mixture and the sequential premix are basically the same, with no new functional group characteristic peaks appearing. This indicates that the premixing process in step S1 is mainly due to hydrogen bonding, physical association, or interfacial adsorption, rather than chemical grafting or the formation of new functional groups. Compared to the single-use mixture, the sequential premix exhibits a higher absorption peak at approximately 3430 cm⁻¹. -1 The broad peak of the -OH / -NH stretching vibration shifts to approximately 3385 cm⁻¹. -1 The broadening of the peak indicates an enhanced interaction between the phenolic and amino groups in polydopamine and the hydroxyl groups in HPC-L and HPC-M; simultaneously, the peak at approximately 1652 cm⁻¹...-1 1608cm -1 and 1515cm -1 The C=O / C=N, C=C / NH, and aromatic ring skeletal vibration peaks at this location have shifted to approximately 1644 cm⁻¹. -1 1600cm -1 and 1508cm -1 This indicates a change in the microenvironment of the polydopamine-related structures; furthermore, approximately 1162 cm -1 1110cm -1 1068cm -1 and 1022cm -1 The COC / CO related absorption peaks in the HPC at that location have shifted to approximately 1154 cm⁻¹. -1 1102cm -1 1058cm -1 and 1015cm -1 This indicates that the ether bonds and hydroxyl groups in the HPC molecular chain participate in interfacial association. These results demonstrate that the sequential premixing method of contacting HPC-M with polydopamine before adding HPC-L enhances the pre-regulation effect of polydopamine on the HPC-M interface, which is beneficial for forming a more stable HPC-L / HPC-M composite gel framework, thereby improving the hydration coordination and structural stability of the coating layer.

[0067] As can be seen from Examples 1 to 4, Comparative Examples 1 to 6 and the above figure, the in vitro cumulative release curves of Examples 1 to 4 are generally flat, with low release rates at 0.5h and 1h, indicating that they can effectively reduce the initial burst release of nifedipine sustained-release tablets; at the same time, the cumulative release rate continues to rise steadily from 4 to 12h, and the release rate at 12h remains at a high level, indicating that it has good sustained release ability in the later stage. In contrast, Control Example 1, lacking polydopamine, suffered from a significant increase in early-stage release due to the difficulty in coordinating the hydration rate differences between HPC-L and HPC-M. Control Example 2, lacking HPC-M, exhibited the fastest release rate due to insufficient gel barrier layer strength, indicating that HPC-M plays a crucial role in the later-stage sustained release. Control Example 3, lacking HPC-L, suffered from insufficient initial wetting and media penetration, resulting in a lower overall release rate, demonstrating that relying solely on HPC-M would lead to insufficient release. Control Example 4, not employing the sequential premixing method of contacting polydopamine with HPC-M first, exhibited a faster release curve than the examples, indicating that sequential premixing is beneficial for improving the coordination of the composite gel framework. Control Examples 5 and 6, lacking PVP K30 and hydrophilic nano-silica respectively, showed decreased release stability, indicating that film continuity and microporous structure uniformity also affect the sustained-release effect. It can be seen that this application achieves a comprehensive effect of low initial release, stable inhibition and full release in the coating layer through the synergistic effect of HPC-L / HPC-M composite gel framework, polydopamine interface coordination, PVP K30 film formation and hydrophilic nano silica microstructure regulation.

[0068] Based on Examples 1 to 4, Comparative Examples 1 to 6, and Tables 1 to 4, it can be seen that the initial burst release rate of Examples 1 to 4 was controlled between 15.2% and 21.4%, the water absorption and swelling rate from 0.5 to 4 hours was generally within the range of 32.5% to 118.6%, the erosion rate from 0.5 to 4 hours was within the range of 1.8% to 12.8%, and the solid content deviation of the coated slurry after standing for 24 hours was only 1.50% to 2.62%. This indicates that the system of the examples can take into account moderate hydration, low erosion, and good slurry stability. Taking Example 1 as an example, its initial burst release rate at 1 hour was 18.6%, significantly lower than that of Control Example 1 (30.6%), Control Example 2 (42.8%), Control Example 4 (27.8%), Control Example 5 (29.5%), and Control Example 6 (26.2%), indicating that polydopamine, HPC-M, sequential premixing, PVP K30, and hydrophilic nano-silica all contribute to inhibiting the initial burst release. The erosion rate of Example 1 at 4 hours was 11.6%, lower than that of Control Example 1 (22.4%), Control Example 2 (31.8%), Control Example 4 (21.6%), Control Example 5 (28.4%), and Control Example 6 (25.2%), indicating that its composite gel skeleton and film structure are more stable. The solid content deviation of Example 1 was only 1.51%, significantly lower than that of Control Example 1 (6.63%), Control Example 4 (8.14%), Control Example 5 (13.47%), and Control Example 6 (24.25%), indicating that its slurry dispersion uniformity and anti-settling properties are better. Although the initial burst release rate of Control Example 3 was only 10.6% and the erosion rate was low, its water absorption and swelling rate was significantly lower. This indicates that the lack of HPC-L resulted in insufficient initial wetting and media penetration of the coating layer, which easily led to insufficient release initiation and could not represent the ideal sustained-release effect. Examples 1 to 4, through the synergistic effect of the HPC-L / HPC-M composite gel framework, the coordination of polydopamine sequential premixing interface, PVP K30 film formation, and the dispersion stabilization of hydrophilic nano-silica, made the coating layer superior to the control examples in reducing initial burst release, maintaining structural stability, and improving slurry stability.

[0069] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A coating composition for nifedipine sustained-release tablets, characterized in that, By weight, including: Hydroxypropyl cellulose (HPC-L) 20–60 parts; Hydroxypropyl cellulose (HPC-M) 10–50 parts; Polydopamine 0.1–15 parts; Polyvinylpyrrolidone (PVP) K30: 1-20 parts; Hydrophilic nano-silica Aerosil 200 Pharma 0.1-10 parts.

2. The coating composition for nifedipine sustained-release tablets according to claim 1, characterized in that, The weight ratio of hydroxypropyl cellulose HPC-L to hydroxypropyl cellulose HPC-M is 1:(0.3-2); the total weight ratio of polydopamine to hydroxypropyl cellulose HPC-L and hydroxypropyl cellulose HPC-M is (0.005-0.25):

1.

3. The coating composition for nifedipine sustained-release tablets according to claim 1, characterized in that, The average particle size of the hydrophilic nano-silica Aerosil 200 Pharma is 5–50 nm.

4. A method for preparing a coating composition for nifedipine sustained-release tablets according to any one of claims 1 to 3, characterized in that, Includes the following steps: S1. Polydopamine, hydroxypropyl cellulose HPC-L, and hydroxypropyl cellulose HPC-M are added to a mixing device for premixing to obtain a composite gel skeleton premix. S2. Polyvinylpyrrolidone (PVP) K30 and hydrophilic nano-silica Aerosil 200 Pharma are added to the composite gel skeleton premix obtained in step S1 and mixed and dispersed to obtain a coating composition.

5. The preparation method according to claim 4, characterized in that, In step S1, the premixing speed is 200–1500 rpm and the mixing time is 5–60 min.

6. The preparation method according to claim 4, characterized in that, In step S1, polydopamine is pre-mixed with hydroxypropyl cellulose HPC-M and then mixed with hydroxypropyl cellulose HPC-L.

7. A coating preparation process for nifedipine sustained-release tablets, characterized in that, Includes the following steps: P1. Provides nifedipine sustained-release tablet cores; P2. The coating composition according to any one of claims 1 to 3 is formulated into a coating slurry; P3. Spray the coating paste onto the surface of the tablet core; P4. The coated tablet cores are dried and cured to obtain nifedipine sustained-release tablets.

8. The coating preparation process according to claim 7, characterized in that, In step P3, a multi-spray gun synchronous spraying method is used for coating; during the spraying process, the core temperature is controlled at 35-50℃, the inlet air temperature at 50-65℃, and the outlet air temperature at 40-55℃.

9. The coating preparation process according to claim 8, characterized in that, The drying and curing process in step P4 includes a low-temperature pre-curing stage and a high-temperature drying stage; the temperature of the low-temperature pre-curing stage is 35-45℃ and the time is 10-60 min; the temperature of the high-temperature drying stage is 45-70℃ and the time is 20-120 min.

Images