Technological Innovation Leads the Development of Pharmaceutical Butyl Rubber Plugs

The production history of butyl rubber plugs dates back to 1957 in Japan. Several economically developed countries such as Europe and the United States also began mass production of pharmaceutical butyl rubber stoppers in early 1970. Foreign pharmaceutical butyl rubber stopper production enterprises not only have obvious advantages in the conformity and stability of product quality, but also have huge investment in technology research and development. New innovations in new materials, new processes, and new equipment emerge in endlessly.

China's pharmaceutical butyl rubber plug production began in 1983, but the introduction of complete sets of equipment and technology to form industrial scale production is in the 90s of last century, currently has more than 50 companies with production registration certificate. Due to the flow of personnel and various forms of communication, the homogenization of equipment processes and the homogeneity of product quality in the industry are obvious, while the investment in technology research and development is relatively small. Therefore, the long-term development of the domestic butyl rubber plug industry must rely on larger scientific research investment.

The latest developments in research and development in the butyl rubber plug industry at home and abroad mainly include the following aspects:

1. Research on ultra-clean rubber, special materials, formulas and processes. These studies are mainly to ensure the quality requirements of certain special sensitive drugs, such as some chemical and biologically active cephalosporin powder preparations, strong acid and alkaline infusion preparations, and complex Chinese medicine preparations. Judging from the formulation of butyl rubber stoppers, raw rubber and some excipients are fat-soluble substances, which may also contain low-molecular-weight substances. If these substances remain in the process of producing rubber plugs, they may enter the drugs after encapsulating the drugs. Physisorption occurs, resulting in a decrease in the solubility of water-soluble drugs and a decrease in clarity or even turbidity. So choose ultra-clean rubber and a simple and clean vulcanization system, using stable and effective production equipment and processes to produce clean rubber plugs that meet more pharmaceutical requirements.

2, coating, coating or coating rubber plug. That is, a new insulation film is added on the surface of the plug. According to the classification of film-forming materials, there are mainly: the use of PTFE membrane material or ETFE film on the rubber plug to local film, the use of PET polyester film on the rubber plug to local film, coated polydimethylsiloxane film Rubber plug, fluorinated polymer formed by vacuum plating "Omniflex" full soft coating, vacuum deposited poly-p-xylene film rubber plug. Overall, this increased barrier film can reduce the interaction between rubber stoppers and sensitive drugs and can exhibit good drug compatibility. It should be pointed out that the barrier film is not "universal", it can reduce the migration of low molecular weight substances into drugs, and can reduce the diffusion of drugs adsorbed on the surface of the bottle stopper into the stopper, but it cannot be completely eliminated. The film thickness, material, and the adhesion process between the film and the rubber plug matrix determine the effectiveness of the coating.

3. Low-particle silicone oil or silicone-free butyl rubber plugs. Butyl rubber plugs are usually siliconized at a certain amount of silicone oil before leaving the factory. However, tests have shown that the silicone oil on the surface of the rubber plug is a polar molecule that can easily be adsorbed when it comes in contact with certain cephalosporin powders, thus hindering the normal dissolution of the powder and causing turbidity. At the same time, silicone oil is also very likely to cause excessive particulates during rubber plug inspection. Therefore, the use of a new type of silicone oil optimizes the silicidation process so that it can be firmly attached to the surface of the rubber plug, which can improve its performance. In foreign countries, there are companies first to siliconize the surface of the vulcanized film, that is, use the temperature or ultraviolet light to cure the appropriate silicon-fluorine material for spraying, so as to form a relatively strong silicon-fluorine coating, so that the rubber plug does not need to be added when cleaning. Silicone oil.

4, RfS sterilized rubber stopper. The RfS sterilized stoppers are packaged in special sterilizable bags. This package allows the stoppers to be directly sterilized without any additional pretreatment during use. RfS sterilized bags are made of high density polyethylene and Tyvek. Tyvek's excellent water vapor permeability makes it an ideal packaging material for steam sterilizing rubber stoppers. RfS sterilized packaging is also suitable for ethylene oxide sterilization but not for dry heat sterilization. It should be pointed out that the RfS sterilized rubber stopper is not only a TYVEK bag and water for injection can be cleaned, the most important is the entire process design, production quality management, product quality stability, physical and chemical biological indicators of the verification and cure Wait.