A film-coated rubber stopper for pharmaceutical packaging and a method for manufacturing the same

Abstract

The present application relates to the technical field of film-coated rubber stopper, and particularly relates to a film-coated rubber stopper for medicine packaging and a preparation method thereof, which comprises the following steps: forming a rubber stopper base body with a preset shape according to a pre-process and performing plasma activation treatment according to initial activation parameters; spraying an interface adhesive on the rubber stopper base body according to an initial spraying amount determined based on an actual roughness and initial spraying parameters; determining a regulated spraying pressure based on a relationship that a coating thickness deviation rate of the interface adhesive is greater than or equal to a risk thickness deviation rate; and pressing a film-coating material and the rubber stopper base body together according to an initial hot-pressing parameter determined based on the coating thickness deviation rate. The present application can fuse detection parameters in the preparation process of the film-coated rubber stopper, comprehensively judge the quality tendency of the prepared film-coated rubber stopper, and then dynamically optimize the relationship between product quality and preparation efficiency, so as to ensure the consistency of product performance.

Description

Technical Field

[0001] This invention relates to the field of coated rubber stopper technology, and more particularly to a coated rubber stopper for pharmaceutical packaging and its preparation method. Background Technology

[0002] As a component of sealing devices in pharmaceutical packaging, coated rubber stoppers are in frequent direct contact with pharmaceuticals, which has a significant impact on the quality and stability of the drugs. Therefore, it is necessary to cover their surface with an inert film to improve their performance, ensure the stability of the drug's properties, and prevent changes in the drug's properties due to adsorption or leakage. Thus, the performance stability of coated rubber stoppers has an important influence on the stability of drug properties.

[0003] Chinese Patent Application Publication No. CN120840098A discloses a coating process for butyl rubber stoppers, belonging to the field of butyl rubber stopper preparation technology. During processing, similar to existing technologies, a film strip is first used to activate the bonding surface with the compounded rubber sheet. Then, the bonding surface of the film strip is covered and fixed to one side of the uncured compounded rubber sheet by adhesion. The key is that during the covering and fixing process, the film strip is conveyed forward by floating on a flowing liquid surface, and during this conveying process, it adheres and is fixed to the compounded rubber sheet above it. This avoids the film strip being pulled like a belt in a conventional belt drive, ensuring that the film strip is not torn or damaged.

[0004] However, the coating process of the butyl rubber stopper still has the following problems: it cannot integrate the parameters obtained in the preparation of the coated rubber stopper, comprehensively judge the quality tendency of the prepared coated rubber stopper, dynamically optimize the relationship between product quality and preparation efficiency, and ensure the consistency of product performance. Summary of the Invention

[0005] Therefore, the present invention provides a coated rubber stopper for pharmaceutical packaging and its preparation method, which overcomes the problem in the prior art that it is impossible to integrate the parameters obtained in the preparation process of the coated rubber stopper, comprehensively judge the quality tendency of the prepared coated rubber stopper, dynamically optimize the relationship between product quality and preparation efficiency, and ensure the consistency of product performance.

[0006] To achieve the above objectives, the present invention provides a method for preparing a coated rubber stopper for pharmaceutical packaging, comprising:

[0007] A rubber stopper substrate of a preset shape is formed according to the pre-process and then subjected to plasma activation treatment according to the initial activation parameters, wherein the initial activation parameters include initial power and initial treatment time.

[0008] Based on the fact that the actual surface roughness of the rubber plug matrix is ​​not within the risky roughness range, it is determined that plasma activation treatment will be performed again.

[0009] An interfacial adhesive is sprayed onto the rubber stopper substrate with an initial spraying amount determined based on the actual roughness, combined with initial spraying parameters, wherein the initial spraying parameters include initial spraying speed and initial spraying pressure.

[0010] The initial spraying pressure is determined based on the relationship that the coating thickness deviation rate of the interface binder is greater than or equal to the risk thickness deviation rate.

[0011] The coating material is pressed together with the rubber stopper substrate using initial hot-pressing parameters determined according to the coating thickness deviation rate, wherein the initial hot-pressing parameters include initial hot-pressing pressure and initial hot-pressing duration;

[0012] Whether to perform re-pressing is determined based on the relationship between the delamination rate of the coating material and the rubber stopper matrix and the risk delamination rate.

[0013] Based on the comprehensive evaluation parameters exceeding the preset evaluation parameters, the hot pressing pressure and hot pressing time of the secondary pressing are adjusted according to the comprehensive excess value.

[0014] The comprehensive evaluation parameters are determined based on the actual roughness, coating thickness deviation rate, and delamination rate.

[0015] The overall excess value is determined based on the overall evaluation parameters and the preset evaluation parameters.

[0016] Furthermore, based on the fact that the actual roughness is not within the preset roughness range, the processing time is adjusted according to a first deviation rate, wherein the first deviation rate is determined based on the actual roughness and the endpoint of the corresponding preset roughness range.

[0017] Furthermore, in response to the actual roughness not being within the risk roughness range, the initial power control direction is determined based on the deviation direction of the actual roughness relative to the risk roughness range.

[0018] Furthermore, based on the fact that the coating thickness deviation rate is greater than or equal to a preset thickness deviation rate, the subsequent spraying speed is adjusted according to a second deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the preset thickness deviation rate.

[0019] Furthermore, in response to adjusting the spraying pressure, based on the coating thickness deviation rate being greater than or equal to the risk thickness deviation rate, the spraying pressure is reduced according to a second deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the risk thickness deviation rate.

[0020] Furthermore, based on the delamination ratio being greater than or equal to a preset delamination ratio, the initial hot-pressing pressure is increased according to a third deviation rate, wherein the third deviation rate is determined based on the delamination ratio and the preset delamination ratio.

[0021] Furthermore, the process of determining hot-pressing failure based on the delamination ratio includes,

[0022] By comparing the delamination rate with the preset delamination rate, the hot pressing failure can be determined.

[0023] In response to the determination that the hot pressing has not failed, it is determined that a second pressing will be performed according to the initial hot pressing parameters.

[0024] Furthermore, in response to the adjustment of the hot pressing pressure and hot pressing time of the secondary pressing, based on the comprehensive evaluation parameter being greater than the preset evaluation parameter, the hot pressing pressure and hot pressing time of the secondary pressing are increased according to the comprehensive excess value.

[0025] Furthermore, in response to the actual roughness being within a preset roughness range and the coating thickness deviation rate being less than a preset thickness deviation rate, and the delamination ratio being less than a preset delamination rate, the initial processing time and initial hot pressing time are reduced according to a preset time adjustment amount.

[0026] The present invention also provides a method for preparing a coated rubber stopper for pharmaceutical packaging, the coated rubber stopper comprising the following components in the following weight ratios: 70-75 parts of halogenated butyl rubber, 8-10 parts of high abrasion-resistant carbon black, 4-5 parts of silica, 2-3 parts of light calcium carbonate, 3-5 parts of paraffin oil, 1-2 parts of vulcanizing agent, and 0.5-1 part of activator.

[0027] Compared with the prior art, the beneficial effect of the coated rubber stopper for pharmaceutical packaging and its preparation method of the present invention is that it can comprehensively judge the quality tendency of the prepared coated rubber stopper by integrating the detection parameters in the preparation process of the coated rubber stopper, and then dynamically optimize the relationship between product quality and preparation efficiency, thereby ensuring the consistency of product performance.

[0028] Furthermore, when sealing the bottle containing the medicine with a coated rubber stopper, the stopper ensures that the medicine is not absorbed or diluted, thus preventing deviations in its performance, when the medicine is not in use. During liquid injection, the syringe is inserted into the lower part of the rubber stopper, where the upper part is wider than the lower part, and guided by the central groove and the lower conical shape, preventing misalignment of the syringe insertion. After liquid injection, when dispensing the medicine, the syringe is guided by the shape of the rubber stopper when it is withdrawn. The friction of the rubber stopper causes the corresponding conical profile, which is wider at the top and narrower at the bottom, to deform towards the cylindrical outer profile on the rubber stopper base. This changes the shape from a conical profile with a wider top and narrower bottom to a conical profile with a narrower top and wider bottom. Therefore, when the bottle containing the medicine is inverted, the deformed part of the rubber stopper can guide the liquid inside the bottle. Compared to the flat surface of a traditional coated rubber stopper that contacts the medicine, the conical guiding surface increases the convergence of the liquid, allowing for more complete output of the medicine, reducing the amount of liquid residue inside the bottle, and increasing the effective utilization rate of the medicine.

[0029] Furthermore, by detecting the surface roughness of the rubber stopper substrate after plasma activation treatment, and using surface roughness to reflect surface energy and adhesion performance, the actual roughness is judged to meet activation qualification by setting a roughness range. The parameters of the current plasma activation treatment are adjusted to ensure that the rubber stopper substrate after plasma activation treatment has good adhesion, thereby ensuring effective bonding of the coating in subsequent processing and preventing the film from detaching from the rubber stopper. Compared with the traditional activation treatment of the rubber stopper substrate with fixed plasma activation parameters, fixed parameter activation cannot detect and reduce insufficient activation performance in time, resulting in persistently insufficient surface energy and adhesion performance of the rubber stopper substrate. In the case of excessive activation performance, the activation time cannot be adjusted to speed up production efficiency. This embodiment can adjust the plasma activation treatment time in time when insufficient activation is detected, thereby adjusting the effect of plasma activation treatment, ensuring that the surface of the rubber stopper after plasma activation treatment has good surface energy and adhesion performance, and thus ensuring that the film can fully and completely adhere to the rubber stopper during subsequent coating processing, meeting the requirements for use in pharmaceutical packaging.

[0030] Furthermore, in cases where activation is deemed unqualified, the current activation effect is further assessed. The actual roughness is determined using a risk roughness range to ascertain whether the current plasma activation treatment negatively impacts the adhesion of the rubber stopper substrate to subsequent coating processes. If the current plasma activation treatment on the rubber stopper substrate is deemed insufficient or excessive, the radio frequency power of the plasma activation treatment is adjusted to regulate its effectiveness. This ensures intelligent and automatic control in the event of uncontrolled plasma activation, guaranteeing that the adjusted plasma-activated rubber stopper possesses good surface energy and adhesion properties. This, in turn, ensures that the film adheres well to the rubber stopper during subsequent coating processes, meeting the requirements for use in pharmaceutical packaging.

[0031] Furthermore, based on the actual roughness of the surface energy and adhesion performance of the rubber stopper substrate reflected by the pre-processing plasma activation treatment, the initial spraying amount of the interfacial adhesive is intelligently determined, thereby reducing performance defects caused by the plasma activation treatment not reaching the target state. After the interfacial adhesive is sprayed, the coating thickness deviation rate is further judged according to the preset thickness deviation rate to determine the spraying qualification. If the coating thickness deviation rate exceeds the preset thickness deviation rate, the spraying speed is adjusted according to the second deviation rate, thereby extending the residence time of the interfacial adhesive on the rubber stopper surface by reducing the spraying speed, promoting the reaction between the interfacial adhesive and the polar functional groups on the surface of the rubber stopper substrate, enhancing the interfacial bonding force, and thus promoting the effective adhesion of the interfacial adhesive. This further improves the yield of the film and rubber stopper in the subsequent coating process. The intelligent automatic feedback adjustment can adaptively control the abnormalities affecting product quality during the preparation of coated rubber stoppers, realizing intelligent production of coated rubber stoppers, optimizing the production rhythm, and optimizing the production rhythm while ensuring the quality of the prepared coated rubber stoppers. This avoids reducing production efficiency by ensuring the quality of coated rubber stoppers through fixed production rhythm.

[0032] Furthermore, in cases where the coating is deemed unqualified, intelligent control of the spraying speed compensates for performance defects caused by insufficient plasma activation treatment. Simultaneously, it further determines whether the current interface adhesive coating is in a failed state. When failure is detected, the spraying speed is adjusted, and the spraying pressure is further controlled to reduce the impact of the interface adhesive on the rubber stopper substrate, preventing adhesive rebound and ensuring uniform spreading of the interface adhesive on the activated surface of the rubber stopper. This reduces the coating thickness deviation rate and guarantees the coating effect during subsequent processing of coated rubber stoppers. This approach differs from traditional fixed-parameter interface adhesive spraying. Compared to traditional spraying processes, this system can automatically adjust spraying parameters when the coating thickness deviation rate exceeds the risk deviation rate. This prevents the continuation of spraying even when the coating is substandard. It can adjust the spraying speed when a substandard coating occurs, and continue to adjust the spraying pressure in the event of a spraying failure. This slows down the production pace of the coated rubber stoppers to ensure their quality and prevents an increase in the defect rate due to excessive pursuit of production speed. By automatically adjusting the parameters during the spraying process, it dynamically coordinates the spraying quality and efficiency, ensuring the stability of the spraying process and the performance stability of the interface adhesive after spraying.

[0033] Furthermore, while optimizing the spraying amount to compensate for the shortcomings of plasma activation treatment not reaching the target state, the initial hot-pressing pressure is further optimized to compensate for the shortcomings of interface adhesive spraying not reaching the target state. Increasing the initial hot-pressing pressure makes the film and rubber stopper adhere more tightly. In the subsequent hot-pressing process, it can further compensate for the performance defects caused by insufficient pre-processing, ensuring that a single hot-pressing process can produce a product that meets the requirements for use in pharmaceutical packaging. After the hot-pressing process is completed, the adhesion state of the film and rubber stopper is tested. The delamination rate is used to determine the hot-pressing qualification by setting a delamination rate. If it is deemed unqualified, the initial hot-pressing pressure is further increased and adjusted. The pressing process is controlled through pre-processing. After a single pressing is completed, the pressing result is further fed back to adjust the parameters of the next pressing process, thereby continuously optimizing the film and rubber stopper bonding and the preparation of coated rubber stoppers. While ensuring the quality of coated rubber stoppers, the production rhythm is continuously optimized, thereby accelerating the preparation efficiency.

[0034] Furthermore, if the current hot pressing is deemed unqualified and the resulting coated rubber stopper is also unqualified, the judgment is further refined to determine whether the defective product completed by the current hot pressing can be subjected to secondary pressing in order to reduce the waste of raw materials. If the hot pressing is determined to be ineffective, it indicates that the current hot-pressed product no longer meets the requirements for secondary pressing to compensate for performance defects and should be disposed of as waste. This is to prevent coated rubber stoppers that have temporarily compensated for performance defects through secondary pressing but still pose safety hazards from entering the market, causing contamination or leakage of the packaged medicine, altering the performance of the medicine, and avoiding serious situations caused by the packaged medicine.

[0035] Furthermore, by constructing comprehensive evaluation parameters in the event of any non-compliance judgment among activation qualification, spraying qualification, and hot pressing qualification, the degree of non-compliance of multiple preparation processes such as activation, spraying, and hot pressing is comprehensively determined. Targeted comprehensive evaluation parameter thresholds, i.e., preset evaluation parameters, are set to judge the preparation quality of the currently prepared coated rubber stopper. In the case of comprehensive preparation non-compliance, secondary pressing is used to reduce performance defects caused by failure to achieve the target effect during the preparation process. At the same time, by intelligently adjusting the secondary pressing parameters based on the comprehensive excess value, the effect of hot pressing composite processing is further enhanced, ensuring that products that meet the secondary pressing requirements can achieve the target state of the coated rubber stopper through secondary pressing, guaranteeing the performance stability of the prepared coated rubber stopper, and reducing the use of coated rubber stoppers with potential performance problems in drug packaging.

[0036] Furthermore, by optimizing the production rhythm during the current production process of coated rubber stoppers, assuming that the preparation effects of multiple production steps such as activation, spraying, and hot pressing are all deemed qualified, redundant parameters in the preparation of coated rubber stoppers can be avoided, which would slow down the preparation efficiency. Thus, by intelligently optimizing the production rhythm of coated rubber stoppers, the preparation efficiency of coated rubber stoppers can be improved while ensuring production quality. Attached Figure Description

[0037] Figure 1 This is a flowchart illustrating a method for preparing a coated rubber stopper for pharmaceutical packaging according to an embodiment of the present invention;

[0038] Figure 2 This is a flowchart illustrating the process of determining activation qualification in an embodiment of the present invention;

[0039] Figure 3 This is a flowchart illustrating the determination of activation failure in an embodiment of the present invention;

[0040] Figure 4 This is a flowchart for determining the spraying effect in an embodiment of the present invention. Detailed Implementation

[0041] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0042] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0043] Please see Figure 1 As shown, it is a flowchart of the method for preparing a coated rubber stopper for pharmaceutical packaging according to an embodiment of the present invention;

[0044] The present invention provides a method for preparing a coated rubber stopper for pharmaceutical packaging, comprising:

[0045] Step S1: Form a rubber stopper substrate of a preset shape according to the pre-process and perform plasma activation treatment according to the initial activation parameters, wherein the initial activation parameters include initial power and initial treatment time;

[0046] Specifically, the pre-process includes,

[0047] Step S11: The rubber compound is mixed, opened and filtered to produce a uniform rubber compound.

[0048] Step S12: Cut the rubber compound into pieces according to specifications;

[0049] Step S13: The cut rubber compound is molded into a pre-shaped mold and then vulcanized to form a rubber stopper matrix.

[0050] Please see Figure 2 As shown, it is a flowchart for determining the activation qualification in an embodiment of the present invention;

[0051] Step S2: Based on the fact that the actual roughness of the rubber stopper substrate surface is not within the risk roughness range, it is determined to perform plasma activation treatment again;

[0052] Specifically, based on the fact that the actual roughness is not within the preset roughness range, the processing time is adjusted according to a first deviation rate, wherein the first deviation rate is determined based on the actual roughness and the endpoint of the preset roughness range corresponding to it.

[0053] Based on the fact that the actual roughness is not within the preset roughness range, an activation failure determination is made.

[0054] The low-temperature vacuum radio frequency plasma treatment equipment performs plasma activation treatment on the bottom surface and part of the side surface of the rubber stopper substrate. The surface profilometer detects the surface roughness of the rubber stopper substrate to determine the actual roughness. The actual roughness is compared with the preset roughness range to determine the activation qualification. If the actual roughness is within the preset roughness range, the activation is deemed qualified; if the actual roughness is not within the preset roughness range, the activation is deemed unqualified.

[0055] The preset roughness range is determined based on the quality statistics of coated rubber stoppers corresponding to different micro-roughnesses after plasma activation treatment of the rubber stopper substrate. It is a value determined by combining historical data statistics and laboratory tests. Historical data statistics consist of test records collected over a consecutive 6-month period of testing of coated rubber stoppers prepared using the same equipment model, rubber batch, and plasma treatment parameters from the same production line. Five rubber stopper substrates are randomly selected from each batch, and their surface roughness after plasma activation and quality indicators such as peel strength, sealing performance, and film adhesion rate after final coating are measured.

[0056] Before processing the interfacial bonding layer on the rubber stopper substrate, the area to be processed needs to undergo plasma activation treatment. The plasma, containing a large number of highly active particles such as ions, electrons, free radicals, and ultraviolet photons, performs a synergistic physical and chemical modification treatment on the rubber stopper substrate surface under the influence of a radio frequency electric field. The physical action thoroughly removes residual mold release agents, plasticizers, organic contaminants, and weak interfacial layers from the previous processing, forming an atomically clean surface. Simultaneously, it induces nanoscale micro-etching on the surface, increasing surface roughness and specific surface area, forming a mechanical anchoring structure, and providing good adhesion for subsequent coatings and adhesives. The synergistic chemical modification treatment uses high-energy active particles in the plasma to break the CH and CC chemical bonds on the rubber surface, generating surface-active free radicals. These free radicals react with oxygen plasma in an oxygen-containing atmosphere, forming a surface layer on the rubber surface. In situ introduction of polar functional groups such as hydroxyl (-OH), carboxyl (-COOH), and carbonyl (C=O) transforms the rubber surface from low surface energy and hydrophobicity to high surface energy and hydrophilicity, significantly improving surface wettability and reactivity. This ensures effective and uniform adhesion of the interface adhesive applied during subsequent processing. Changes in the surface roughness of the rubber stopper substrate fully reflect the improved adhesion effect of plasma activation treatment. Good adhesion is observed in surface roughness between 0.1 μm and 0.2 μm, while a surface roughness less than 0.02 μm indicates insufficient activation, minimal roughness improvement, and poor adhesion. A surface roughness greater than 0.5 μm indicates excessive etching, resulting in a weak interface layer and microcracks, reducing adhesion and sealing performance. Therefore, a preset roughness range of 0.1 μm to 0.2 μm (inclusive) is used.

[0057] The radio frequency power is between 200W and 250W, with 220W preferred as the initial power. The processing time ranges from 60 to 120 seconds, with 90 seconds preferred as the initial processing time. The vacuum chamber pressure is set between 30Pa and 80Pa, with 60Pa preferred as the initial vacuum chamber pressure. The gas type is preferably a mixture of oxygen and argon, with a flow ratio of O2:Ar = 1:2 to 1:3, preferably O2:Ar = 1:2.5. The total gas flow ranges from 20sccm to 40sccm, preferably 30sccm. The initial distance between the rubber stopper and the vacuum chamber wall is 60mm for plasma activation treatment.

[0058] When the actual roughness is within the preset roughness range, the activation is deemed qualified, indicating that the current plasma activation treatment effectively increases the micro-roughness of the rubber stopper substrate surface and improves surface wettability and reactivity, thereby enhancing the adhesion performance of the rubber stopper substrate surface; it can ensure uniform adhesion when the interface adhesive is sprayed subsequently, without the need for parameter adjustment of the low-temperature vacuum radio frequency plasma treatment equipment.

[0059] When the actual roughness does not fall within the preset roughness range, and activation is deemed unqualified, it indicates that the current plasma activation treatment on the rubber stopper substrate surface is insufficient to achieve the target adhesion performance. In this case, further evaluation of the rubber stopper substrate surface activation effect is needed to determine if the current surface adhesion can be compensated for by subsequent processes, ultimately ensuring that the performance of the coated rubber stopper meets the product target requirements. At this point, the number of activation failures is recorded. When consecutive activation failures occur, the initial processing time is adjusted. Since a single activation failure may be due to quality issues with the rubber stopper substrate itself or an occasional error, a set number of consecutive failures is established for each activation failure. For example… The initial consecutive failure count is set to 3. When the consecutive failure count reaches 3, the processing time is adjusted. The processing time is adjusted according to the first deviation rate of the actual roughness relative to the corresponding boundary. For example, if the current detected actual roughness is 0.08μm, which is less than the minimum value of the preset roughness range of 0.1μm, the first deviation rate is (0.1-0.08) / 0.1=20%, and the processing time is adjusted from the initial processing time of 90s to 108s according to the first deviation rate. If the current detected actual roughness is 0.22μm, which is greater than the maximum value of the preset roughness range of 0.2μm, the first deviation rate is (0.22-0.2) / 0.2=10%, and the processing time is adjusted from the initial processing time of 90s to 81s according to the first deviation rate.

[0060] By setting a continuous number of failure determinations, it is ensured that the activation failure is indeed due to the activation parameters of the low-temperature vacuum radio frequency plasma processing equipment failing to make the actual roughness fall within the preset roughness range, thus determining the activation as qualified. By setting different base values ​​for the first deviation rate when the actual roughness deviates from the preset roughness range, when the current activation is determined to be unqualified and the actual roughness is less than the minimum value of the preset roughness range, the processing time is significantly adjusted to ensure that the activation state after parameter adjustment can be determined as qualified. When the actual roughness is greater than the maximum value of the preset roughness range, the processing time is slightly adjusted to avoid the activation effect rapidly decreasing from over-activation to under-activation due to excessively rapid adjustment of the processing time.

[0061] The preset-shaped rubber stopper substrate is a rotary rubber stopper substrate with an upper cylindrical outer contour, a middle upper small and lower large protrusion contour, a lower upper large and lower small conical contour, and a groove in the middle.

[0062] This invention, by sealing the bottle containing the medicine with a coated rubber stopper, ensures that the medicine is not absorbed or diluted when not in use, thus preventing deviations in its performance. During liquid injection, the syringe is inserted into the lower part of the rubber stopper, where the upper part is wider than the lower part and the lower part has a tapered shape. The central groove and the lower tapered shape guide the syringe, preventing insertion deviations. After liquid injection, when dispensing the medicine, the syringe is removed without contact with the coated rubber stopper. The friction of the stopper causes the corresponding conical profile, which is larger at the top and smaller at the bottom, to deform towards the cylindrical outer profile on the rubber stopper base. This changes the shape from a larger-at-the-top, smaller-at-the-bottom conical profile to a smaller-at-the-top, larger-at-the-bottom conical profile. Therefore, when the bottle containing the medicine is inverted, the deformed part of the rubber stopper can guide the liquid inside the bottle. Compared to the flat surface of a traditional coated rubber stopper that contacts the medicine, the conical guiding surface increases the convergence of the liquid, allowing for more complete output of the medicine, reducing the amount of liquid residue inside the bottle, and increasing the effective utilization rate of the medicine.

[0063] This invention detects the surface roughness of a rubber stopper substrate after plasma activation treatment. Surface roughness reflects surface energy and adhesion performance. The actual roughness is assessed within a preset roughness range to determine activation qualification. The parameters of the current plasma activation treatment are adjusted to ensure good adhesion of the plasma-activated rubber stopper substrate. This ensures effective bonding of the coating during subsequent processing and prevents film detachment from the rubber stopper. Compared to traditional methods that use fixed plasma activation parameters, where insufficient activation cannot be detected or mitigated, leading to persistently low surface energy and adhesion, and excessive activation cannot be adjusted to speed up production, this invention can promptly adjust the plasma activation time when insufficient activation is detected, thereby regulating the effect of the plasma activation treatment. This ensures that the surface of the rubber stopper after plasma activation treatment has good surface energy and adhesion performance, ensuring that the film fully and completely adheres to the rubber stopper during subsequent coating processing, meeting the requirements for pharmaceutical packaging.

[0064] Please see Figure 3 As shown, it is a flowchart for determining activation failure in an embodiment of the present invention;

[0065] Specifically, in response to the actual roughness not being within the risk roughness range, the initial power control direction is determined based on the deviation direction of the actual roughness relative to the risk roughness range.

[0066] The activation failure is determined by comparing the actual roughness with the risk roughness range. If the actual roughness falls within the risk roughness range, the activation is determined to be successful. If the actual roughness does not fall within the risk roughness range, the activation is determined to be unsuccessful.

[0067] The risk roughness range is determined based on the degree of influence of plasma activation treatment on the adhesion of the rubber stopper substrate. When the surface roughness is less than 0.05 μm, it indicates that the current plasma activation treatment can no longer meet the surface adhesion requirements of the rubber stopper substrate. If plasma activation is still performed according to the current parameters, even secondary activation cannot achieve the target activation state. When the surface roughness is greater than 0.3 μm, it indicates that there is currently excessive etching, and the surface may produce a weak interface layer and microcracks. At this time, if only the processing time is adjusted, the processing time needs to be adjusted from 90s to 45s, which is lower than the lower limit of the processing time range of 60-120s. Therefore, the risk roughness range is set to 0.05 μm-0.3 μm to ensure strict judgment on the activation timeliness.

[0068] When the actual roughness falls within the risk roughness range, and the activation is determined to be not ineffective, it indicates that although the current activation state is unqualified, the current deficiency can still be compensated for through subsequent processing to ensure the performance of the rubber stopper after coating.

[0069] When the actual roughness is outside the risk roughness range and activation is deemed ineffective, the initial RF power needs to be re-determined based on the current first deviation rate. If the current actual roughness is 0.04 μm, (0.1-0.04) / 0.1=60%, and the first deviation rate is 60%, then the RF power is adjusted from 220W to 286W, with the adjustment rate being half of the first deviation rate. If the current actual roughness is 0.4 μm, (0.4-0.2) / 0.2=100%, and the first deviation rate is 100%, then the RF power is adjusted from 220W to 110W to avoid excessive etching that could create a weak interface layer and microcracks, reducing adhesion and sealing. Simultaneously, the processing time is restored to the initial processing time to allow for further adjustment after re-determining activation compliance following RF power adjustment. Furthermore, rubber stopper substrates with actual roughness less than the minimum risk roughness range undergo secondary activation treatment, while rubber stopper substrates with actual roughness greater than the maximum risk roughness range directly proceed to the next processing step.

[0070] In cases where activation is deemed unqualified, this invention further assesses the current activation effect by determining the actual roughness within a risk roughness range. This determines whether the current plasma activation treatment negatively impacts the adhesion of the rubber stopper substrate to the subsequent coating process. If the plasma activation treatment on the rubber stopper substrate is deemed insufficient or excessive, the radio frequency power of the plasma activation treatment is adjusted to regulate its effectiveness. This ensures intelligent and automatic control even when the current plasma activation effect is out of control, guaranteeing that the plasma-activated rubber stopper possesses good surface energy and adhesion properties. This, in turn, ensures that the film adheres well to the rubber stopper during subsequent coating processes, meeting the requirements for use in pharmaceutical packaging.

[0071] Step S3: Apply an interfacial adhesive to the rubber stopper substrate with an initial coating amount determined based on the actual roughness and initial coating parameters, wherein the initial coating parameters include initial coating speed and initial coating pressure.

[0072] Step S4: Determine the spraying pressure based on the relationship that the coating thickness deviation rate of the interface binder is greater than or equal to the risk thickness deviation rate.

[0073] Please see Figure 4 As shown, it is a flowchart for determining the spraying effect in an embodiment of the present invention;

[0074] Specifically, the spraying speed is adjusted according to a second deviation rate based on the coating thickness deviation rate being greater than or equal to a preset thickness deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the preset thickness deviation rate.

[0075] Based on the coating thickness deviation rate being greater than or equal to the preset thickness deviation rate, a coating failure determination is made. Second deviation rate = Coating thickness deviation rate - Preset thickness deviation rate.

[0076] The spraying images of the activated area of ​​the rubber stopper are acquired in real time by an online visual inspection device. The coating thickness deviation rate is determined by an image recognition algorithm based on the initial spraying amount and the theoretical coating thickness determined by the activated area of ​​the rubber stopper. The coating thickness deviation rate is compared with the preset thickness deviation rate to determine the qualification of the spraying. If the coating thickness deviation rate is less than the preset thickness deviation rate, the spraying is deemed qualified. If the coating thickness deviation rate is greater than or equal to the preset thickness deviation rate, the spraying is deemed unqualified.

[0077] The preset thickness deviation rate is determined based on the thickness after spraying the current initial spray amount under the target state and the thickness deviation rate when it has no impact on the coating effect. When the thickness deviation rate is 4 to 5%, it does not affect the subsequent coating effect. Therefore, the preset thickness deviation rate is set to 5% to determine the spraying qualification.

[0078] The spraying amount ranges from 0.8 to 1.2 g / m². 2 1g / m 2 The preset spraying amount is determined by a spraying pressure range of 0.3–0.5 MPa, preferably 0.4 MPa, and a spraying speed of 5–8 cm / s, preferably 6 cm / s. The ambient temperature is 18–25°C, and the relative humidity is 40%–60%. The initial spraying amount is determined based on a first deviation rate combined with the preset spraying amount. For example, if the current actual roughness is 0.08 μm, the first deviation rate is 20%, and the upper limit of the preset spraying amount adjustment rate is 30%, then the preset spraying amount is set to half of the first deviation rate, which would be 1 g / m². 2 The value was adjusted to 1.1 g / m 2 As an initial coating amount, it increases the contact area between the interfacial adhesive and the substrate, thus compensating for insufficient adhesion.

[0079] When the coating thickness deviation rate is less than the preset thickness deviation rate, it indicates that the current interface adhesive is effectively and uniformly adhered to the target area of ​​the rubber stopper substrate, and the coating is deemed qualified, without the need for parameter adjustment.

[0080] When the coating thickness deviation rate is greater than or equal to the preset thickness deviation rate, it indicates that the current coating effect of the interface adhesive cannot reach the target state, and the coating is judged to be unqualified. At this time, it is necessary to adjust the spraying speed according to the second deviation rate of the coating thickness deviation rate relative to the preset thickness deviation rate. If the current coating thickness deviation rate is 6%, the second deviation rate = coating thickness deviation rate - preset thickness deviation rate, and the second deviation rate is 1%, then the spraying speed is reduced by 10% from the initial spraying speed of 6cm / s. The ratio of the spraying speed adjustment rate to the second deviation rate is 8:1 to 12:1. In this embodiment, it is taken as 10:1. Under the condition that the ratio of the spraying speed adjustment rate to the second deviation rate is met, it is convenient to calculate and control, and the spraying speed can be adjusted to a minimum of 3cm / s. In the case of judging that the coating is unqualified, it is necessary to further determine whether the current spraying state seriously affects the coating effect of the rubber stopper.

[0081] This invention intelligently determines the initial coating amount of the interfacial adhesive based on the actual roughness of the rubber stopper substrate, reflecting the surface energy and adhesion performance of the pre-processed plasma activation treatment. This reduces performance defects caused by the plasma activation treatment not reaching the target state. After the interfacial adhesive is coated, the coating thickness deviation rate is further judged according to a preset thickness deviation rate to determine the coating qualification. If the coating thickness deviation rate exceeds 5% of the preset thickness deviation rate, the spraying speed is adjusted according to a second deviation rate. This reduces the spraying speed, prolongs the residence time of the interfacial adhesive on the rubber stopper surface, promotes the reaction between the interfacial adhesive and the polar functional groups on the surface of the rubber stopper substrate, enhances the interfacial bonding force, and promotes the effective adhesion of the interfacial adhesive. This further improves the yield of the film and rubber stopper in subsequent coating processing. The intelligent automatic feedback adjustment can adaptively control the process during the preparation of coated rubber stoppers to address anomalies affecting product quality. This achieves intelligent production of coated rubber stoppers, optimizes the production rhythm, and optimizes the production rhythm while ensuring the quality of the prepared coated rubber stoppers. This avoids reducing production efficiency by fixing the production rhythm to ensure the quality of the coated rubber stoppers.

[0082] Specifically, in response to adjusting the spraying pressure, based on the coating thickness deviation rate being greater than or equal to the risk thickness deviation rate, the spraying pressure is reduced according to a second deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the risk thickness deviation rate.

[0083] The coating thickness deviation rate is compared with the risk thickness deviation rate to determine the failure of the spraying. If the coating thickness deviation rate is less than the risk thickness deviation rate, the spraying is considered not to have failed. If the coating thickness deviation rate is greater than or equal to the risk thickness deviation rate, the spraying is considered to have failed.

[0084] The risk thickness deviation rate is determined based on the thickness after spraying with the current initial spraying amount under the target condition and the thickness deviation rate under the influence of the coating effect. At this time, the risk thickness deviation rate is 10%. When the coating thickness deviation rate reaches 10%, if the negative influence of spraying continues to accumulate, it will affect the performance of the rubber stopper after coating.

[0085] When the coating thickness deviation rate is greater than or equal to the risk thickness deviation rate, the spraying is deemed to have failed. The current spraying parameters have caused the spraying effect to deviate from the target spraying effect. If the spraying effect continues to deteriorate, it may cause the subsequent coating process of the rubber stopper to fail. Therefore, at this time, it is necessary to adjust the spraying pressure according to the second deviation rate. The maximum adjustment rate of the spraying pressure is 25%. Therefore, the maximum adjustment rate of the spraying pressure is matched with the second deviation rate. It is set that whenever the second deviation rate increases by 1%, the spraying pressure is reduced by 3% accordingly. This reduces the spraying impact force of the interface adhesive, avoids the interface adhesive from rebounding, and ensures that the interface adhesive is evenly spread on the activated surface of the rubber stopper, thereby reducing the coating thickness deviation rate and ensuring the coating effect when processing the coated rubber stopper in the subsequent process.

[0086] This invention, when determining that the coating is unqualified, compensates for performance defects caused by insufficient plasma activation treatment by intelligently controlling the spraying speed. Simultaneously, it further determines whether the current interface adhesive coating is in a failed state. When the coating is determined to be ineffective, it further adjusts the spraying pressure while controlling the spraying speed to reduce the impact of the interface adhesive on the rubber stopper substrate, preventing interface adhesive rebound and ensuring that the interface adhesive is evenly spread on the activated surface of the rubber stopper. This reduces the coating thickness deviation rate and ensures the coating effect during subsequent processing of coated rubber stoppers. Compared with traditional fixed spraying parameters for interface adhesive spraying, this invention offers significant advantages. When the coating thickness deviation rate exceeds the risk thickness deviation rate, the spraying parameters can be automatically adjusted. This avoids the situation in traditional spraying processes where spraying continues even when the coating is unqualified. The spraying speed can be adjusted when the coating is unqualified. In the case of spraying failure, the spraying pressure can be adjusted to slow down the production pace of the coated rubber stoppers to ensure their qualification and prevent the increase in defect rate caused by excessive pursuit of production pace. By automatically adjusting the parameters in the spraying process, the spraying quality and efficiency can be dynamically coordinated to ensure the stability of the spraying process and the performance stability of the interface adhesive after spraying.

[0087] Step S5: Press the coating material with the rubber stopper substrate using the initial hot-pressing parameters determined according to the coating thickness deviation rate, wherein the initial hot-pressing parameters include the initial hot-pressing pressure and the initial hot-pressing duration;

[0088] Step S6: Determine whether to perform re-pressing based on the relationship between the delamination ratio of the coating material and the rubber stopper matrix and the risk delamination rate.

[0089] Specifically, based on the delamination ratio being greater than or equal to a preset delamination ratio, the initial hot-pressing pressure is increased according to a third deviation rate, wherein the third deviation rate is determined based on the delamination ratio and the preset delamination ratio.

[0090] Images of the rubber stopper coating are acquired using online visual inspection equipment to determine the delamination rate. The delamination rate is then compared with a preset delamination rate to determine the hot pressing qualification. If the delamination rate is less than the preset delamination rate, the hot pressing is deemed qualified; if the delamination rate is greater than or equal to the preset delamination rate, the hot pressing is deemed unqualified.

[0091] The preset delamination rate is determined to be 1% according to the qualification standard, which is used to fully determine whether the current hot-pressing composite is qualified;

[0092] When the delamination rate is less than the preset delamination rate, the hot pressing is deemed qualified, indicating that the current hot pressing is qualified. The hot pressing composite processing of the coating and the rubber stopper matrix can still be carried out according to the current parameters.

[0093] When the delamination rate is greater than or equal to the preset delamination rate, the hot pressing is deemed unqualified. This indicates that the current hot pressing composite parameters are insufficient to hot press the coating and the rubber stopper matrix to the target state. Further analysis is needed to determine whether the hot pressing is out of control. It is determined that the initial hot pressing pressure should be increased. Whenever the delamination rate increases by 1%, the initial hot pressing pressure should be increased by 0.01 MPa.

[0094] The hot pressing temperature is generally set between 80 and 120°C, with 90 to 100°C being the preferred heating range and 95°C being the preferred initial hot pressing temperature. The hot pressing pressure is generally set between 0.15 and 0.3 MPa, with 0.2 to 0.25 MPa being the preferred pressure range. The preset hot pressing pressure is 0.2 MPa, which corresponds to a coating thickness deviation rate of less than 5%. Whenever the coating thickness deviation rate increases by 1% (less than 1% is counted as 1%), the initial hot pressing pressure increases by 0.01 MPa. The hot pressing time is generally set between 30 and 60 seconds, with 45 seconds being the preferred initial hot pressing time.

[0095] This invention compensates for the shortcomings of plasma activation treatment in achieving the target state by optimizing the spraying amount, and further compensates for the shortcomings of interfacial adhesive spraying in achieving the target state by optimizing the initial hot-pressing pressure. Increasing the initial hot-pressing pressure makes the film and rubber stopper adhere more tightly. In the subsequent hot-pressing process, it can further compensate for the performance defects caused by insufficient pre-processing, ensuring that a single hot-pressing process can produce a product that meets the requirements for use in pharmaceutical packaging. After the hot-pressing process is completed, the adhesion between the film and rubber stopper is tested. The delamination rate is used to determine the hot-pressing qualification by setting a delamination rate. If the qualification is not met, the initial hot-pressing pressure is further increased and adjusted. The pressing process is controlled by the pre-processing. After a single pressing is completed, the pressing result is further fed back to adjust the parameters of the next pressing process, thereby continuously optimizing the film-rubber stopper bonding and the preparation of coated rubber stoppers. While ensuring the quality of coated rubber stoppers, the production rhythm is continuously optimized, thereby accelerating the preparation efficiency.

[0096] Specifically, the process of determining hot-pressing failure based on the delamination ratio includes:

[0097] By comparing the delamination rate with the preset delamination rate, the hot pressing failure can be determined.

[0098] In response to the determination that the hot pressing has not failed, it is determined that a second pressing will be performed according to the initial hot pressing parameters.

[0099] The hot pressing failure is determined by comparing the delamination rate with the risk delamination rate. If the delamination rate is less than the risk delamination rate, the hot pressing is considered not to have failed. If the delamination rate is greater than or equal to the risk delamination rate, the hot pressing is considered to have failed.

[0100] The risk delamination rate is determined based on the delamination percentage when secondary pressing is prohibited. Secondary pressing is prohibited when the delamination percentage is 5%.

[0101] When the delamination rate is less than the risk delamination rate, it is determined that the hot pressing has not failed. This indicates that although the current pressing state is unqualified, it can still be compensated by a second pressing. The second pressing is carried out according to the initial hot pressing parameters.

[0102] When the delamination rate is greater than or equal to the risk delamination rate, it is determined that the hot pressing has failed. This indicates that the current pressing state is in a failed state, and the current coating is prohibited from being pressed again. The coated rubber stopper prepared in this case is treated as a defective product and is discarded.

[0103] In cases where the current hot pressing is deemed unqualified and the resulting coated rubber stopper is also unqualified, this invention further refines the judgment to determine whether the defective product completed by the current hot pressing can be subjected to secondary pressing, thereby reducing the waste of raw materials. When it is determined that the hot pressing has failed, it indicates that the current hot-pressed product no longer meets the requirements for secondary pressing to compensate for performance defects, and it is treated as waste. This avoids the use of coated rubber stoppers that have temporarily compensated for performance defects through secondary pressing but still pose safety hazards, causing contamination or leakage of the packaged medicine, altering the performance of the medicine, and preventing serious situations caused by the packaged medicine.

[0104] Step S7: Based on the comprehensive evaluation parameter being greater than the preset evaluation parameter, the hot pressing pressure and hot pressing time of the secondary pressing are adjusted according to the comprehensive excess value, wherein...

[0105] The comprehensive evaluation parameters are determined based on the actual roughness, coating thickness deviation rate, and delamination rate.

[0106] The overall excess value is determined based on the overall evaluation parameters and the preset evaluation parameters.

[0107] Specifically, in response to the adjustment of the hot pressing pressure and hot pressing time of the secondary pressing, based on the comprehensive evaluation parameter being greater than the preset evaluation parameter, the hot pressing pressure and hot pressing time of the secondary pressing are increased according to the comprehensive excess value.

[0108] A comprehensive evaluation parameter is constructed based on the first deviation rate, the second deviation rate, the delamination ratio, and the third deviation rate relative to the preset delamination rate, along with their corresponding weighting coefficients. The comprehensive evaluation parameter is compared with the preset evaluation parameter to determine the overall preparation qualification. If the comprehensive evaluation parameter is less than or equal to the preset evaluation parameter, the comprehensive preparation is deemed qualified. If the comprehensive evaluation parameter is greater than or equal to the preset evaluation parameter, the comprehensive preparation is deemed unqualified.

[0109] The third deviation rate is determined based on the difference between the delamination ratio and the preset delamination rate. Let the comprehensive evaluation parameter be Z, the preset evaluation parameter be Zi, the first deviation rate be H, the second deviation rate be J, and the third deviation rate be S, with weighting coefficients α, β, and γ respectively. Then, Z = α × H + Kj × β × J + Ks × γ × S, where Kj and Ks are correction coefficients, adjusting J and S to the same order of magnitude as H to prevent invalid parameters from appearing during the determination of the comprehensive evaluation parameter Z, thus avoiding numerical distortion and affecting the accuracy of the judgment. The values ​​of Kj and Ks are typically in the range of 5–12. Therefore, to facilitate calculation, Kj is... The values ​​of Ks are both set to 10; while α, β, and γ are determined according to the degree of influence of each value on the overall quality of the prepared coated rubber stopper. Among them, the delamination ratio directly affects the hot pressing qualification judgment result of the coated rubber stopper, and directly reflects whether the product is qualified. Therefore, its weight coefficient γ is set to 0.5. Plasma activation treatment affects surface energy and adhesion strength. It is a pre-processing process for interfacial adhesive spraying and directly affects the adhesion effect after interfacial adhesive spraying. Therefore, α has a greater influence on the overall quality of the prepared coated rubber stopper than β. Therefore, α is set to 0.3 and β is set to 0.2.

[0110] For example, if the current actual roughness is 0.06μm, then the first deviation rate is 40%, the coating thickness deviation rate is 8%, the second deviation rate is 3%, the delamination rate is 2.5%, and the third deviation rate is 1.5%. Z = α×H + Kj×β×J + Ks×γ×S = 0.3×40% + 10×0.2×3% + 10×0.5×1.5% = 25.5%;

[0111] The preset evaluation parameters are determined based on the corresponding values ​​of each parameter indicating a deterioration trend during the preparation of the coated rubber stopper. Based on empirical considerations, when the actual roughness is 0.08 μm, the first deviation rate is 20%; or when the actual roughness is 0.25 μm, the first deviation rate is 25%, at which point signs of deterioration begin to appear. Therefore, 20% is selected as the value for constructing the preset evaluation parameters. Signs of deterioration begin to appear when the coating thickness deviation rate is 8%, and when the delamination rate is 2%. Therefore, Zi = α × H + Kj × β × J + Ks × γ × S = 0.3 × 20% + 10 × 0.2 × 3% + 10 × 0.5 × 1% = 17%.

[0112] At this point, if the comprehensive evaluation parameter exceeds the preset evaluation parameter, the comprehensive preparation is deemed unqualified, indicating that the current comprehensive preparation is unqualified. In this case, it is necessary to adjust the hot pressing pressure and hot pressing time according to the comprehensive excess value of the comprehensive evaluation parameter exceeding the preset evaluation parameter. If the current comprehensive excess value is 8.8%, then the hot pressing pressure is adjusted from the currently detected 0.22MPa and increased by 8.8% to 0.24MPa, and the hot pressing time is adjusted from 45s and increased by 8.8% to 48.96s.

[0113] When the comprehensive evaluation parameter is less than or equal to the preset evaluation parameter, and the comprehensive preparation is deemed qualified, the secondary pressing process is not triggered. If the secondary pressing is triggered due to the risk delamination rate being greater than or equal to the preset delamination rate, then the secondary pressing is performed according to the initial pressing parameters.

[0114] This invention constructs comprehensive evaluation parameters when any of the activation, spraying, and hot-pressing qualification results are deemed unqualified. This allows for a comprehensive assessment of the degree of unqualification in multiple preparation processes, including activation, spraying, and hot-pressing. Targeted comprehensive evaluation parameter thresholds (preset evaluation parameters) are set to determine the quality of the currently prepared coated rubber stopper. In cases where the overall preparation is deemed unqualified, a secondary pressing is performed to mitigate performance defects caused by failure to achieve the target effect during the preparation process. Simultaneously, the parameters for the secondary pressing are intelligently adjusted based on the overall excess value to further enhance the effect of the hot-pressing composite processing. This ensures that products meeting the secondary pressing requirements can achieve the target state of the coated rubber stopper through secondary pressing, guaranteeing the performance stability of the prepared coated rubber stopper and reducing the use of coated rubber stoppers with potential performance issues in pharmaceutical packaging.

[0115] Specifically, in response to the actual roughness being within a preset roughness range, the coating thickness deviation rate being less than a preset thickness deviation rate, and the delamination ratio being less than a preset delamination rate, the initial processing time and initial hot pressing time are reduced according to a preset time adjustment amount.

[0116] The preset time adjustment amount is usually set to 0-5s. In this embodiment, the preset time adjustment amount is set to 3s to avoid instability of the corresponding plasma activation treatment effect and hot-pressing composite effect due to excessive adjustment of the initial processing time and initial hot-pressing time. When the qualification judgment is qualified, the initial processing time is adjusted from 90s to 87s, and the initial hot-pressing time is adjusted from 45s to 42s. The minimum value of the initial processing time is 60s. When the initial processing time is adjusted to 60s, the adjustment is stopped. The minimum value of the initial hot-pressing time is 30s. When the initial hot-pressing time is adjusted to 30s, the adjustment is stopped.

[0117] This invention optimizes the production rhythm during the current production process of coated rubber stoppers, ensuring that the preparation effects of multiple production steps such as activation, spraying, and hot pressing are all qualified. This avoids redundant parameters in the preparation of coated rubber stoppers that would slow down the preparation efficiency. By intelligently optimizing the production rhythm of coated rubber stoppers, the preparation efficiency of coated rubber stoppers is improved while ensuring production quality.

[0118] This embodiment also relates to a method for preparing a coated rubber stopper for pharmaceutical packaging. The coated rubber stopper comprises the following components in the following weight ratios: 70-75 parts of halogenated butyl rubber, 8-10 parts of high abrasion-resistant carbon black, 4-5 parts of silica, 2-3 parts of light calcium carbonate, 3-5 parts of paraffin oil, 1-2 parts of vulcanizing agent, and 0.5-1 part of activator.

[0119] Halogenated butyl rubber is preferably one of chlorinated butyl rubber or brominated butyl rubber; high abrasion-resistant carbon black is preferably the commonly used type N330; vulcanizing agent is preferably phenolic resin; and activator is preferably zinc oxide.

[0120] Example 1: 72 parts of brominated butyl rubber, 9 parts of high abrasion-resistant carbon black N330, 4.5 parts of silica, 2.5 parts of light calcium carbonate, 4 parts of paraffin oil, 1.5 parts of phenolic resin, and 0.8 parts of zinc oxide;

[0121] Test results: Hardness: 48; Tensile strength: 11.2 MPa; Elongation at break: 420%; Strength change rate under hot air aging at 121℃ for 24 hours: -8.5%; Elongation change rate: -12%; Insoluble microparticles: meets pharmacopoeia requirements; Volatile substances: qualified; Puncture debris: no obvious debris; Sealing performance: 100% qualified; Compatibility with drug solution: qualified.

[0122] Example 2: 70 parts of brominated butyl rubber, 10 parts of high abrasion-resistant carbon black N330, 5 parts of silica, 2 parts of light calcium carbonate, 3 parts of paraffin oil, 2 parts of phenolic resin, and 1 part of zinc oxide.

[0123] Test results: Hardness: 52; Tensile strength: 12.8 MPa; Elongation at break: 380%; Hot air aging, 121℃×24h: Strength change rate: -6.2%; Elongation change rate: -9%; Insoluble microparticles: meet pharmacopoeia requirements; Volatile substances: qualified; Puncture debris: meets standards; Sealing performance: 100% qualified; Compatibility with drug solution: qualified.

[0124] Example 3: 75 parts of brominated butyl rubber, 8 parts of high abrasion-resistant carbon black N330, 4 parts of silica, 3 parts of light calcium carbonate, 5 parts of paraffin oil, 1 part of phenolic resin, and 0.5 parts of zinc oxide;

[0125] Test results: Hardness: 45; Tensile strength: 9.8 MPa; Elongation at break: 460%; Hot air aging, 121℃×24h: Strength change rate: -10%; Elongation change rate: -15%; Insoluble microparticles: Excellent grade; Volatile substances: Extremely low, meeting the requirements for biological products; Puncture debris: None; Sealing performance: Qualified; Compatibility with drug solution: Excellent.

[0126] Example 4: 65 parts of brominated butyl rubber, 12 parts of high abrasion-resistant carbon black N330, 6 parts of silica, 2.5 parts of light calcium carbonate, 6 parts of paraffin oil, 3 parts of phenolic resin, and 1 part of zinc oxide;

[0127] Test results: Hardness: 62; Tensile strength: 7.8 MPa; Elongation at break: 280%; Under hot air aging at 121℃ for 24 hours: Strength change rate: -18%; Elongation change rate: -25%; Insoluble particles: Qualified; Volatile substances: Qualified; Puncture debris: Obvious debris; Sealing performance: 98%, qualified; Compatibility with drug solution: Slight turbidity appeared in some drug solutions.

[0128] Example 5: 68 parts of brominated butyl rubber, 6 parts of high abrasion-resistant carbon black N330, 2 parts of silica, 1 part of light calcium carbonate, 5 parts of paraffin oil, 1 part of phenolic resin, and 1 part of zinc oxide.

[0129] Test results: Hardness: 38; Tensile strength: 6.5 MPa; Elongation at break: 510%; Under hot air aging at 121℃ for 24 hours: Strength change rate: -22%; Elongation change rate: -30%; Insoluble particles: Qualified; Volatile substances: Qualified; Puncture debris: Slight debris; Sealing performance: 96%, qualified; Compatibility with drug solution: Qualified.

[0130] The preferred formulation range of this invention is the key boundary for ensuring the overall performance of the coated rubber stopper. Examples 1 to 3 all exhibit good mechanical properties, excellent hot air aging stability, complete sealing pass rate, and satisfactory drug solution compatibility within this range, meeting the high-requirement packaging needs of injectable and biological products. However, Example 4, due to excessive carbon black and insufficient rubber, resulted in a brittle and hard rubber compound, significantly increasing the rate of strength change after aging, exhibiting obvious puncture and chipping, and decreased sealing performance. Example 5, due to insufficient carbon black and reinforcement failure, resulted in insufficient tensile strength, severe strength deterioration after aging, and a reduced sealing pass rate. These counterexamples verify that deviating from the preferred formulation range directly leads to significant deterioration of the coated rubber stopper in terms of mechanical strength, aging resistance, sealing reliability, and puncture performance, failing to meet the comprehensive requirements of high-requirement pharmaceutical packaging for safety, cleanliness, and long-term stability.

[0131] This invention achieves a synergistic balance between mechanical properties, heat aging resistance, cleanliness, sealing performance, and drug compatibility by optimizing the ratio of halogenated butyl rubber, reinforcing fillers, and processing aids in the coated rubber stopper. The tensile strength of the coated rubber stopper can reach 9.8–12.8 MPa, and the elongation at break is between 380% and 460%. After hot air aging at 121℃ for 24 hours, the changes in strength and elongation are controlled at -6.2% to -10% and -9% to -15%, respectively, exhibiting both good strength and toughness and thermal stability. Simultaneously, the insoluble microparticles meet pharmacopoeia standards, the volatile substance content is low, puncture shedding is minimal, the sealing performance is 100% qualified, and the compatibility with drug solutions is excellent. This invention can meet the comprehensive requirements of safety, cleanliness, and long-term stability for high-demand pharmaceutical packaging such as injectables and biological products.

[0132] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a coated rubber stopper for pharmaceutical packaging, characterized in that, include, A rubber stopper substrate of a preset shape is formed according to the pre-process and then subjected to plasma activation treatment according to the initial activation parameters, wherein the initial activation parameters include initial power and initial treatment time. Based on the fact that the actual surface roughness of the rubber plug matrix is ​​not within the risky roughness range, it is determined that plasma activation treatment will be performed again. An interfacial adhesive is sprayed onto the rubber stopper substrate with an initial spraying amount determined based on the actual roughness, combined with initial spraying parameters, wherein the initial spraying parameters include initial spraying speed and initial spraying pressure. The initial spraying pressure is determined based on the relationship that the coating thickness deviation rate of the interface binder is greater than or equal to the risk thickness deviation rate. The coating material is pressed together with the rubber stopper substrate using initial hot-pressing parameters determined according to the coating thickness deviation rate, wherein the initial hot-pressing parameters include initial hot-pressing pressure and initial hot-pressing duration; Whether to perform re-pressing is determined based on the relationship between the delamination rate of the coating material and the rubber stopper matrix and the risk delamination rate. Based on the comprehensive evaluation parameters exceeding the preset evaluation parameters, the hot pressing pressure and hot pressing time of the secondary pressing are adjusted according to the comprehensive excess value. The comprehensive evaluation parameters are determined based on the actual roughness, coating thickness deviation rate, and delamination rate. The overall excess value is determined based on the overall evaluation parameters and the preset evaluation parameters.

2. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, Since the actual roughness is not within the preset roughness range, the processing time is adjusted according to the first deviation rate, wherein the first deviation rate is determined based on the actual roughness and the endpoint of the corresponding preset roughness range.

3. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, In response to the actual roughness not being within the risk roughness range, the initial power control direction is determined based on the deviation direction of the actual roughness relative to the risk roughness range.

4. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, The subsequent spraying speed is adjusted based on the coating thickness deviation rate being greater than or equal to a preset thickness deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the preset thickness deviation rate.

5. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, In response to adjusting the spraying pressure, based on the coating thickness deviation rate being greater than or equal to the risk thickness deviation rate, the spraying pressure is reduced according to a second deviation rate, wherein the second deviation rate is determined based on the coating thickness deviation rate and the risk thickness deviation rate.

6. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, Based on the delamination ratio being greater than or equal to a preset delamination ratio, the initial hot-pressing pressure is increased according to a third deviation rate, wherein the third deviation rate is determined based on the delamination ratio and the preset delamination ratio.

7. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, The process of determining hot-pressing failure based on the delamination ratio includes: By comparing the delamination rate with the preset delamination rate, the hot pressing failure can be determined. In response to the determination that the hot pressing has not failed, it is determined that a second pressing will be performed according to the initial hot pressing parameters.

8. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, In response to the adjustment of the hot pressing pressure and hot pressing time of the secondary pressing, based on the comprehensive evaluation parameter being greater than the preset evaluation parameter, the hot pressing pressure and hot pressing time of the secondary pressing are increased according to the comprehensive excess value.

9. The method for preparing a coated rubber stopper for pharmaceutical packaging according to claim 1, characterized in that, In response to the actual roughness being within a preset roughness range, the coating thickness deviation rate being less than a preset thickness deviation rate, and the delamination rate being less than a preset delamination rate, the initial processing time and initial hot pressing time are reduced according to a preset time adjustment amount.

10. The coated rubber stopper prepared by the method for preparing a coated rubber stopper for pharmaceutical packaging according to any one of claims 1-9, characterized in that, The coated rubber stopper comprises the following components in the following weight ratios: 70-75 parts of halogenated butyl rubber, 8-10 parts of high abrasion-resistant carbon black, 4-5 parts of silica, 2-3 parts of light calcium carbonate, 3-5 parts of paraffin oil, 1-2 parts of vulcanizing agent, and 0.5-1 part of activator.

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