China has a history of over ten years since the beginning of research on halogenated butyl rubber stoppers. During this brief development process, Chinese manufacturing enterprises have achieved breakthroughs from scratch, experiencing a stage from learning to introducing to developing innovation. Whether it is the localization of raw materials, the gradual improvement of process layout, or the gradual improvement of product quality, all have left a solid footprint for domestic rubber stoppers. With the National Medical Products Administration's increasing efforts to eliminate natural rubber stoppers, more and more pharmaceutical enterprises will choose butyl rubber stoppers for more and more drugs. Therefore, the development of halogenated butyl rubber plugs will become a focus of increasing attention.

1、 Diversification of products

Firstly, the diversification of rubber stopper performance. According to the different properties of various drugs, corresponding specialized rubber stoppers will emerge. For example:

Special drug specific rubber stopper

Strong acid and alkali resistant drugs Acid and alkali resistant rubber plugs

Special rubber stopper for clarity of penicillin, Streptomycin and cephalosporin series drugs

Large infusion coating or coating rubber stopper

Secondly, the coexistence of structural diversification and standardization. In order to meet the different production processes and equipment used by different pharmaceutical companies, the structural design of rubber stoppers will inevitably vary depending on the "machine" and "factory". Therefore, in future development, the matching size and structure of rubber stoppers and equipment will no longer be completely limited to standard requirements, but there may be some "personalized" designs, such as "spherical" neck design, "reinforced" neck design Diversity design of coronal isolators, etc. Nevertheless, in order to meet the requirements of mass production by manufacturing enterprises and bidding procurement by pharmaceutical enterprises, the matching dimensions of rubber stoppers and bottles will be as close as possible to international standards, in order to achieve final standardization and consistency. So, the development trend of rubber stopper structure and size is the coexistence of diversification and standardization.

In addition, with the development of plastic packaging containers, new sealing elastic component structures will emerge. For example, the gaskets for polypropylene bottles (or polyethylene bottles), rubber stoppers matching disposable infusion bags and oral liquid gaskets that have been mass produced at present will account for a considerable proportion in the future halogenated Butyl rubber industry.

The third is price differentiation. Due to the uneven grade of various drugs, their prices vary. Therefore, in order to meet the requirements of high and low grade drugs, rubber stopper manufacturers must provide various rubber stoppers with varying prices.

2、 Research on the Expandability of Formulas and Components

In response to the problems that pharmaceutical companies have encountered in the use of halogenated butyl rubber stoppers over the past decade, various rubber stopper manufacturing enterprises will continue to increase research investment, expand research fields, and find a way out through in-depth research on formulas and components.

The first step is to select the adhesive type.

Halogenated Butyl rubber does have its advantages in chemical inertness and gas tightness, but recent research shows that the stabilizer epoxidized Soybean oil and oligomers added to the rubber during processing are easy to be extracted by drugs. In addition, the calcium ion of Calcium stearate is easy to react with oxalic acid and citric acid in drugs to form insoluble calcium salt, Oxalate and citrate, which may become a factor affecting the clarity of some drugs. Therefore, it has become inevitable to reselect better rubber varieties. According to relevant data, thermoplastic elastomer and EXPPROTM will be superior to existing halogenated Butyl rubber in terms of extraction resistance. Therefore, it will become a trend to try to use these two materials for the rubber stopper industry.

Next is the modification of fillers.

The hydrophilic white filler is extremely difficult to be soaked by the hydrophobic halogenated Butyl rubber, so it is extremely difficult to disperse evenly. By surface treating the filler, the dispersibility can be greatly improved, resulting in the optimal mixing effect and performance of the adhesive.

The third is to improve the purity of other components in the formula.

Due to the inevitable presence of trace metal ions in various minerals in the formula components, which have a significant catalytic effect on automatic oxidation reactions. For example, 0.0002mol/L copper can increase the oxidation rate of vitamin C by 10000 times. Therefore, trying to improve the purity of each component as much as possible will be the research direction of the rubber stopper industry.

3、 Improvement and innovation of production process

1. Control of silicone oil content

Experiments have shown that excessive silicone oil on the surface of rubber stoppers can directly affect the clarity of drugs such as cefazolin sodium. Therefore, controlling and reducing the amount of silicone oil on the surface of rubber stoppers as much as possible will become the direction of efforts for various rubber stopper manufacturing enterprises.

2. Innovation in post-processing technology

In order to meet the requirements of some pharmaceutical companies for the use of rubber stoppers without washing, various rubber stopper manufacturers are trying to improve the surface cleanliness of rubber stoppers by improving the quality of cleaning water, increasing extraction processes, and replacing inner packaging bags, in order to achieve the production of "non washing rubber stoppers" and "non sterilization rubber stoppers". Due to the lack of relevant standards for this type of product at home and abroad, it is not yet possible to conduct performance testing and judgment on this type of product. However, with the development of the butyl rubber plug industry, it is believed that "wash free" and "sterilize free" rubber plugs will eventually become official branches in the butyl rubber plug industry.

4、 Gradual improvement of product standards

With the intensification of market competition, pharmaceutical companies' requirements for halogenated butyl rubber stoppers will continue to increase. Mainly manifested in the following aspects:

1. Particle content

Research has shown that large particles in injection, especially in infusion, can cause local circulatory disorders and cause vascular embolism; Excessive particles can also cause local blockage and insufficient blood supply, resulting in tissue hypoxia and edema and phlebitis. Therefore, the content of halogenated Butyl rubber cork particles in direct contact with the injection will become one of the important quality indicators of the product. The composition of particles is relatively complex, and the identified substances include carbon black, calcium carbonate, zinc oxide, cellulose, paper scraps, clay, glass scraps, bacteria, fungi, silicates, and iron. There are many sources of visible particles, including components in the formula and foreign pollutants. At present, the detection of particles in foreign countries mainly involves the determination of the content of various metal ions. Although there are detection methods for visible and invisible particles in international standards, there are no specific indicators. This indicator has been included in the newly issued standards for chlorinated and brominated butyl rubber stoppers (trial), as it is the first time that the detection method and indicators have been developed together, and it is estimated that there will be an adjustment range. In short, particles are one of the important indicators that must be monitored in the rubber stopper industry, and with the development of the pharmaceutical industry, this indicator will inevitably become more stringent.

2. Residual silicone oil content on the surface

To prevent the rubber plug from sticking during transportation and ensure smooth operation on the machine track, halogenated butyl rubber plugs must be properly silicified during cleaning. But it's not that the larger the amount of silicone oil, the better. The amount of surface silicone oil will directly affect the clarity of certain drugs, so the content of surface silicone oil should be tested. At present, this item is not included in various standards and is estimated to become one of the control indicators for rubber plugs in the future.

3. Compatibility test with drugs

As a packaging material that directly comes into contact with the liquid medicine, rubber stoppers not only adsorb the main drug and antibacterial agent in the solution, but also the vulcanizing agent, filling agent, plasticizer, etc. in its own formula components may be leached out by the liquid medicine, thereby polluting the liquid medicine and reducing its efficacy. Therefore, in order to minimize the impact of rubber stoppers on drugs as much as possible, each rubber stopper manufacturing enterprise must closely cooperate with pharmaceutical enterprises, extensively conduct compatibility tests between halogenated butyl rubber stoppers and drugs, and select qualified formulas for supply.

5、 The centralization trend of manufacturers

With the gradual improvement of the standard for butyl rubber plugs, the market has put forward higher and stricter requirements for the cleanliness of the production environment of manufacturers, the innovation ability of scientific research and development, and the effectiveness of production site management and quality management. Therefore, butyl rubber plug manufacturing enterprises that cannot meet the requirements in terms of management software and hardware construction will gradually be phased out. In the next decade, the enterprise structure will undergo fundamental changes, with a few companies with complete hardware facilities and excellent product quality controlling the entire butyl rubber plug market.

Therefore, all manufacturers of butyl rubber stoppers should closely follow the development trend at home and abroad, adhere to the policy of "producing one generation, developing one generation, and reserving one generation", strive to improve the quality of domestic butyl rubber stoppers, and strive to provide stronger quality assurance for the pharmaceutical industry nationwide. Www.ah-zm.com