Butyl rubber stopper Production of medical technology and technical status quo and development trend

Butyl rubber stopper inside the packaging of drugs is a replacement product, with outstanding chemical stability, gas-tight, low extraction and a good biological performance, for the drug provides a more reliable quality assurance.

First, production technology

At present, the production of butyl rubber cork, there are two main processes:

1. Molding process. At present, domestic manufacturers to adopt most of the molding process, the foreign Stelmi France and Japan's Association for the use of technology.

With rubber mixing (mixing, the chain) chain of hot plates or cut pieces out of pressure tablets weighing sulfide punching bag inside the pre-wash cleaning out

2. Injection process. U.S. West's foreign companies, Belgium Wit's good to adopt the technology.

Article vulcanized rubber mixing with a punching bag inside the pre-wash cleaning out

For molding, the rubber due to poor thermal conductivity, the layer internal temperature slowly increased, a larger temperature difference between inside and outside layer of plastic, when the outer layer of vulcanized rubber into the best stage, the inner layer of rubber vulcanized to start, at a stage of less sulfur. When the inner layer of rubber vulcanized to achieve the best stage, the outer layer of glue has been sulfur. As a result, the greater the temperature difference between inside and outside the plastic layer, the greater the impact on product quality, use of low-temperature curing, both inside and outside layer of plastic can heat up by interference curve, but a significantly longer time to sulfide, which is inefficient. Injection and curing process itself provides a layer of plastic inside and outside the uniform temperature conditions, which gives the possibility of curing temperature.

The butyl rubber medicinal quality of cork, to a large extent depends on the quality of forming sulfide, and the curing (either flat or sulfide injection molding machine sulfide) is critical and important equipment. For butyl rubber with good air tightness and thermal characteristics of the poor liquidity, which requires curing in a relatively short time has let die in a vacuum state repeatedly opened and closed, so that the gas being drawn at the same time, in order to Let melt under the butyl rubber in the cavity flow, so that the plug of uniform thickness of the crown, aircraft sulfide must have a high pressure rubber in the shape when the flow of curing the hot-plate needs to have more The high temperature uniform, as well as the constant temperature stability of the curing time.

DESMA400 and 560 in Injection tonnage sulfide on the plane with the above advantages in the formulation of appropriate curing system, usually about 195 ℃ production, a small bubble of products, the passing rate, high productivity, a more stable size. The domestic rubber plug other plants commonly used in flat-curing, because of equipment and prescription system (usually resin curing) of the reasons, usually in the 170 ~ 180 ℃, the tonnage of 200 to 300, 4 to 8 minutes under the production, productivity Lower. Therefore, the current injection Dingjijiaosai curing process is the development of a trend.

At the same time, the use of professional medical Dingjijiaosai washing machine, the quality of the rubber plug is also crucial. Such as: Germany Huber washing machine equipment as a result of the advantages of having a strong impact, since the cleaning, centrifugal Shuaigan features such as patents, and cleaning time is short, have a clean plastic scrap sericin less accurate than the silicone oil, such as uniform characteristics, so as to ensure Plug the finished product better cleanliness. Of course, from the particles and foreign bodies out on the production, control of the production environment to strengthen and enhance the quality awareness of employees, from the rules and regulations binding on the agenda.

Second, the status quo of domestic technology

Res domestic package has passed the word plug factory has more than 30, are aimed at Dingjijiaosai potential market. However, the quality of products, stability, the personalized needs to work hard on. As the market is not standardized, low-cost quality products occupy a place in the city, resulting in a number of cut-throat competition, so, the State Drug Administration how to grasp this opportunity to cultivate a sound market environment is very crucial. According to the China Pharmaceutical Packaging Association delegation to the Western European manufacturers Yao Baocai the study, Western European manufacturers rubber plug, the intensity of their labor, equipment Yaobao Cai may not be superior to domestic manufacturers, but they plug on the formula ( Plug the high cost of domestic), cleaning the rubber plug, particles controlled the very characteristics, the degree of silicification can be customized according to detect the amount of silicone oil. These are things that we need to work hard.

Third, the development trend of medical cork

1. Stringent product quality requirements and pay attention to the stability of the batch, the invisible particles can be seen and stricter control;

2. Ultra-clean cork to ensure compatibility with the drugs at the time of low extraction.

A. The main raw materials for rubber and choice.

As the formula in a variety of raw materials, the relationship between the existence of concentration gradient, the use of the process, the drug was cork adsorption, absorption, penetration and started to extract, in order to pollution or destruction of drugs, reduce the effects, in particular, strong acidic or alkaline The drug may damage rubber plug. Therefore, in production control precipitates, the choice of high-purity, performance and stability is very important raw materials, but also pay attention to the raw materials of the "solubility parameters", according to the "similar histocompatibility" principle, can reduce the rubber plug in a variety of ingredients Migration, and improve the compatibility of the drug. EXXON company is currently developing EXXPRO rubber, epoxy-free Spodiopogon (ESBO), same as allene oligomers, does not contain antioxidants that can greatly improve the compatibility.

B. coated plastic film or cork

Cork film industry has become a hot spot of development. Outside the West, Helvoet, Japan Society has been a major product, and sales volume, still in its domestic research and development stage. Cork cork coating to improve the compatibility of the drug is better, especially the large infusion cork. Now, the main coating or plastic film technology in three ways: First, plug directly into the surface coating, for not fully fluorinated membranes of polyethylene material, an organic solvent to dissolve after coating; Second, the surface of activated to deal with rubber plug , With graft material for chemical grafting, grafting monomers and precursors in order to plug a total of referral button to connect to reach the surface of inert treatment, choose the right way and excellent coating membranes is related to Important; Third, vacuum plating film approach, in Dingjijiaosai a special coating on the surface of the polymer material.

C. disposable rubber plug (to be sterilized)

Disposable rubber plug in a number of domestic pharmaceutical companies have requested a trial. Usually ordinary Dingjijiaose, pharmaceutical companies need to wash before use of sterilization, and the rubber plug to be sterilization process is as follows: after a rubber plug in line with the standards of the pharmacopoeia clean water, and then injected with the Pharmacopoeia standards Clean water, drying and silicification, and then 100 in the clean environment, cool packaging, packaging bags with a dedicated TYVEK bag directly into the steam sterilization cabinet drawer of sterilization, drying. Disposable rubber plug of the original heat, bacteria and particulate load index to be controlled.

3. The stability of the product size, suitable for high-speed packaging lines

The SDA set YBB standards, no clear standards for the size, but the national standard for size standards, a variety of sizes to gradually prevail ISO and at the same time asked us to die in precision machining and product design effort.

4. Cork to meet the requirements of a variety of physical and chemical properties, with a few crumbs drop.

Acupuncture has become a chip off the large pharmaceutical companies focus of attention, the effects of acupuncture needles is the structure of the crumbs off one of the main factors and the other in the composition of the formula should be a good choice of plasticizers, rubber so that the stretch will be less stress , Acupuncture can reduce the dust off.

5. And the development of the 5th and 6th-generation antibiotics Dingjijiaose good compatibility is also a hot spot; in which genetic engineering drugs, it can not be existing packaging materials packaging.

6. To meet the development of the use of a variety of infusion-therapy drugs, to adapt to a wide range, excellent long-term stability Dingjijiaosai.

7. TPE thermoplastic elastomer rubber plug in the development, is also a hot spot.

All in all, according to the SFDA, "Res injection pipe [2000] No. 462", as stipulated in sodium penicillin injection, Zn penicillin, Penicillium ammonia, sulfur and antibiotics such as streptomycin infusion preparations, oral liquid biological products, blood Products are equal before the end of 2004 to stop using ordinary natural rubber plug all Dingjijiaosai changed, so Dingjijiaose manufacturers have seen this huge market share, but the potential market competition is also very powerful. With the accession to the WTO, foreign large-scale rubber plug plants, such as the West, Helvoet, Stelmi and so on into the domestic market, so in the future Dingjijiaosai of competition in the market focused on product quality, price and marketing services, corporate R & D strength of new products Integrated competitiveness on.