Halogenated butyl rubber stoppers (hereinafter referred to as rubber stoppers) are divided into 4 categories according to cleanliness: rubber stoppers that need to be washed, rubber stoppers that need to be rinsed, rubber stoppers that need to be sterilized, and rubber stoppers that are ready to use The common point is that the production processes in the rubber mixing, vulcanizing and die cutting processes are the same, but they are adjusted according to different products during cleaning.
Based on the actual situation in China, the following are introduced separately.
- rubber stopper to be washed
As the name suggests, this type of rubber stopper requires deep processing before use: it needs to be cleaned and siliconized with dimethyl silicone oil. When cleaning, it is necessary to rinse and finely rinse with a cleaning agent and a large amount of washing water to remove the surface of the rubber plug and the internal foreign matter (fiber, glue, particles, etc.), directly sterilize and dry according to the use, and then package the medicine Or directly encapsulate the drug and finally sterilize it.
The characteristics of this type of product are: the rubber stopper contains medium to high levels of microorganisms, pyrogens, and particulate pollution. The rubber stopper is generally packaged in double-layer sterile bags, plus a layer of corrugated cardboard boxes.
Because the rubber stopper is a complicated process for pharmaceutical companies, it is generally not used domestically or internationally.
- Rubber stopper to be rinsed
This type of rubber stopper is a kind of rubber stopper commonly used in China. Before use, this type of rubber stopper can be used after rinsing with a small amount of hot water, or it can be sterilized, dried, or terminally sterilized.
At present, regular rubber stopper manufacturers generally perform deep-level cleaning during cleaning and perform preliminary sterilization operations. Generally, bacteria endotoxin indicators need to be detected when leaving the factory, so pharmaceutical companies need only simple rinse, but it should be noted that Yes: In some applications, it is necessary to use silicone oil for appropriate silicidation, or to require moderate silicidation of rubber plugs before leaving the factory, especially for powders and freeze-dried products, but to avoid excessive silicification, otherwise it will cause plugging, Affect production efficiency.
- Rubber stopper to be sterilized
Also called rubber plugs to be sterilized or disposable rubber plugs, the common name is RFS (Ready-for-SterilizationClosure), which refers to the rubber plugs that pharmaceutical companies can use only after sterilization after unpacking the product. Prerequisites The rubber plug must be pre-lubricated, the maximum number of particles and non-pyrogenic meet the requirements. It is required to use water for injection (WFI) when cleaning the terminal of the rubber plug production plant. Its characteristics are: it has effectively removed bacterial endotoxin, microbial formation system and visible and invisible particles.
The reason why it can be directly sterilized in the pharmaceutical factory is that this rubber stopper is packed in a special RFS bag. The English name of this bag is ULTRACLEANCLEANSTEAMBAG, sometimes also called BREATHEBAG. The seal of this bag has a sterilization mark, and the color of the mark will change after sterilization. The material of the bag is made of TYVEK on one side and HDPE (high density polyethylene) on the other. TYVEK is a sheet-like structure, formed by a very dense, arbitrary-oriented, continuous high-density polyethylene interconnect fiber. These strong, continuous fibers are combined by heating and pressure during the production process, and The amount of abraded fiber scrap is low, and particles will not be released into the air when worn or opened; and under certain pressure, TYVEK flakes can allow steam or gas to freely enter and exit the product packaging, ensuring the lowest pressure fluctuation in the packaging structure, and Can maintain the sterility of the package. Under 125 ° C high temperature conditions, the size of the package can be kept stable and the package is complete; ETD (ethylene oxide) can also be sterilized.
Therefore, this packaged product greatly facilitates the use of pharmaceutical companies. Under the premise of ensuring product quality, it can reduce or even eliminate the quality control after the rubber stopper is introduced into the factory, eliminating the processes of cleaning, siliconization and drying before use. , And can reduce the invalid inventory in the middle, for small and medium pharmaceutical companies without special cleaning equipment, it has reduced a lot of expenses.
Notes on the use of RFS packaging to be sterilized:
(1) Suitable sterilization methods include: steam sterilization, ethylene oxide sterilization, and Y-ray sterilization, but are not suitable for dry heat sterilization;
(2) It is best to put the TYVEK face up when sterilizing the RFS package in a steam autoclave, so that the best effect of steam penetration and drying during sterilization can be obtained, and the RFS package to be sterilized must be sterilized. Single-layer flat
(3) In order to prevent the generation of particles, the RFS packaging to be sterilized must be cut with sharp scissors after the sterilization process is completed, and the packaging bag must not be torn apart;
(4) As a reference guide, the typical cycling conditions are 121CX20mm moist heat sterilization, and then dried at 80C for 1h.
The key to this type of product is the control of pyrogens, microorganisms, and cleaning water. At present, the international market has a large amount of use, and the domestic market is still in the development and trial production stage. The main reason is that the market use is small and expensive water injection systems are also limited. Development of rubber stopper manufacturers for such products.
This kind of products can be sterilized in 3 ways: steam, ethylene oxide and Y-ray, but the steam will increase the moisture content of the rubber plug, causing potential problems for lyophilized products; The plug will absorb ethylene oxide gas and affect the quality of medicines. Therefore, radiation is generally used for sterilization in foreign countries, but because butyl rubber is not resistant to radiation, the intensity of radiation must be controlled before use. Effective sterilization and protection of rubber plugs from damage.