Membrane technology and application of butyl rubbe

Membrane technology and application of butyl rubber stoppers for glass bottles

although butyl rubber stoppers have good internal cleanliness, chemical stability, air tightness and biological properties, due to the complex formula and the concentration gradient of raw materials, they are absorbed, adsorbed, leached and penetrated by drugs after being sealed with some drugs with strong molecular activity, resulting in the compatibility between rubber stoppers and drugs. Some cephalosporins Some large infusion, as well as many traditional Chinese medicine injection preparations. Therefore, by selecting an inert soft coating to cover the surface of the rubber stopper and isolate the direct contact between the drug and the rubber bottle stopper, the compatibility with the drug can be significantly improved

today, various suitable membrane materials used in butyl rubber bottle stopper are sought by technicians of butyl rubber stopper manufacturers at home and abroad

this article (Zhonghua packaging bottle) makes a simple statement on the current situation and development trend of butyl rubber stopper membrane technology for your colleagues' reference, hoping to enlighten you

I. current situation of membrane technology of butyl rubber stopper

after the coating of butyl rubber stopper, due to its many advantages: for example, by forming a film on the surface of the rubber stopper, it can effectively reduce the absorption, adsorption, leaching and penetration between the rubber stopper and the drug, and improve the long-term stability of the drug. The first customers of ixsenic technology are preparing to mass produce ixsenic technology; Improve the mechanical lubricity of the rubber plug; Greatly reduce the increase of insoluble particles in the drug solution caused by silicone oil

in foreign countries, the production technology of butyl rubber stoppers has developed for a long time. For example, Japan began to produce butyl rubber stoppers in 1957, and various economically developed countries in Europe and the United States also achieved mass production of pharmaceutical butyl rubber stoppers in early 1970; In China, it was not until 1992 that the pharmaceutical butyl rubber bottle stopper was mass produced. At the same time, the film covering technology of butyl rubber plugs has been developed earlier in foreign countries, and the technology is relatively mature. For example, the west company in the United States, Daxia NiTi company in Japan, helvoet company in Belgium, etc., all have different styles of film covering butyl rubber plugs, and all have the capacity of mass production. In China, due to the relatively late development of the membrane technology of butyl rubber plugs, there are not many manufacturers that can mass produce film coated butyl rubber plugs with relatively stable product quality. However, the technicians of domestic butyl rubber plugs manufacturers have been exploring and communicating through a large number of tests, and some manufacturers can mass produce film coated butyl rubber plugs with relatively stable quality. After long-term stability tests of pharmaceutical factories, The long-term stability of the related drug solutions reflects good results, and the registration of new drug packaging materials is under way according to the relevant requirements of order No. 13 of the State Administration. The following is an introduction to the requirements of film materials, types of film materials, various film covering processes and characteristics of film covered butyl rubber plugs

(I) (Zhonghua packaging bottle) requirements for film material of film covered butyl rubber stopper

1), extremely low gas permeability

2), strong water vapor permeability resistance

3), high chemical resistance

4), high heat aging resistance

5), with high internal cleanliness

6), good ozone resistance and weather resistance

7), stable radiation disinfection

8). It should be non-toxic, tasteless and pollution-free

9). It should have good elasticity

(II) commonly used film covering materials

according to the characteristics of film covering materials, the most commonly used film covering materials are the following:

polydimethylsiloxane film

poly-p-xylene film

poly Teflon, ETFE film

polyester film, etc

(III) introduction to various film covering processes of film covered butyl rubber stopper

1. Film coating technology

the film materials used in this technology are mostly poly ETFE film, Teflon film, polyethylene film and polypropylene film. Among them, Teflon membrane is an inert material, and its technical products have been approved by the U.S. Food and Drug Administration (FDA) for use in the food and pharmaceutical industry. Its material characteristics are expressed as the carbon fluorine bond with high bond energy in the molecular structure of fluorine resin. Due to the shielding effect formed by fluorine atoms outside the carbon chain, Teflon has excellent drug resistance; Membrane ETFE (ethylene tetrafluoroethylene copolymer) has good physical and chemical properties. It is a kind of advanced material that not only has the excellent properties of PTFE, but also has polyethylene easy to thermoplastic processing and low price. This membrane has the characteristics of strong flatness and high single-sided activity treatment level. In short, the excellent material properties of fluorinated polymers make it widely used in drug isolation, but its extremely low surface can make it the most difficult polymer to bond. Therefore, it is particularly important to study the surface treatment technology of materials, which is a technology that can make fluorinated polymers strongly adhere to the surface of polymer elastomers

the advantages of the film sticking technology are: the heat sealing process does not use any organic solvents and adhesives, so there is no chemical residue; The film in direct contact with the drug has no surface treatment, and the minimal surface tension can reduce the adsorption of the drug; The film has good compactness, which can ensure the good shielding performance in the production of film and plastic packaging bags and the stability with drugs; The disadvantages are: the adhesion of membrane materials is not strong, the membrane is easy to fall off, the elasticity of membrane materials is poor, the hardness of film covered rubber plug is large, and problems such as poor self sealing and poor needling performance are easy to occur. At the same time, the price is also relatively expensive

coating technology can be divided into three types:

a. The one-time molding method is used to prepare the full film covered rubber plug. The process is as follows:

1), membrane surface activation treatment (chemical or physical method, generally single-sided treatment)

2), film covering on the film (the activated surface of the film material is pasted on the unvulcanized mixed film)

3), vacuum molding vulcanization molding

4), formed rubber plug (which can cover the neck and sealing surface, or the neck and crown)

5), punching

b. The coating rubber plug is prepared by secondary molding method, and the process is as follows:

1), membrane surface activation treatment (chemical, physical)

2), coating on mixed film

3), vacuum molding vulcanization molding

4), neck molding

5), neck punching

6), neck and crown vulcanization bonding molding

7), neck coating molding rubber plug

8), punching

c. This process is to first produce the rubber plug, apply a layer of adhesive on the surface of the rubber plug, press the film into the shape of the rubber plug, and stick it on the rubber plug to press and cure. The key of this technology lies in the choice of adhesive and how to apply it evenly, otherwise there will be peeling or film falling off, which will affect the use

2. Dip coating, spraying and brushing technology

the membrane material used in this technology is usually polydimethylsiloxane membrane, which is a cross-linked dimethylsiloxane oil with appropriate molecular weight and good biological inertia; The butyl cork naturally prevents the adsorption and diffusion of drugs after coating, which provides a guarantee for the quality of drugs; At the same time, the surface of the coated butyl rubber plug is very smooth, and it can be used directly without silicification during cleaning and use, which can reduce the problem of silicone oil particles caused by uneven silicification

the advantages of this technology are: relatively simple process route, low cost, strong market promotion value and strong market competitiveness. The disadvantages are: the obvious defects of the general coating process are that if the process operation skills are poor, sagging and slight uneven film thickness are easy to occur in the vertical and inclined parts of the butyl rubber plug

the usual process route of this technology is: Vulcanized film activation treatment → vulcanized film grafting treatment → coating process → room temperature curing → high temperature curing → curing after cooling

3. Vacuum coating process

the coating material used in this process on butyl rubber stopper is usually poly-parylene film. There are usually three varieties of parylene polymers: parylene n Polychlorinated p-xylene (parylene C) and polychlorinated p-xylene (parylene d). They have different characteristics and advantages. Their main differences are deposition rate, service temperature and dielectric loss factor. Parylene polymer is a high-purity coating material with good chemical inertia and good biocompatibility. It has been approved by FDA and has been widely used in various medical devices and packaging materials

the advantages of vacuum coating technology are: because parylene is a unique polymer with post thermal plasticity, parylene coating process is carried out at room temperature and vacuum, so it can penetrate and cover the object to be treated, and the film formation is uniform and transparent; Because it is a dry process, there is no catalyst or organic solvent, no sagging, loss and other common coating defects of liquid coating. It is a real pinhole free coating film, which can be moisture-proof, acid proof, alkali proof, bacteria proof, weather resistant, high temperature resistant (the use temperature is as high as 275 degrees) and cold resistant (minus 200 degrees)

the requirements of vacuum coating technology are to select and use special vacuum coating equipment to ensure that the performance of the equipment meets the process requirements

the technical route of the vacuum coating process is:

parylene deposition process

p-xylene active monomer poly p-xylene

evaporation chamber cracking chamber deposition chamber cold trap vacuum pump

parylene deposition process is the leading step to evaporate the solid raw material p-xylene at about 150 ℃, and the second step is to split the two side chain carbon chains at 680 ℃ to form stable active monomers, Finally, the active monomer enters the deposition chamber at room temperature for polymerization and deposition, and is instantly adsorbed on the substrate and polymerized into a poly-p-xylene film. The remaining gas is captured by the cold trap to avoid sediment entering the vacuum pump

II. Development trend of butyl rubber stopper film technology

according to the above introduction (Zhonghua packaging bottle), combined with the current situation of the use of butyl rubber stopper film technology at home and abroad, butyl rubber stopper with good film-forming performance is obtained, with the following development trend:

1. The elasticity and flexibility of the membrane are good, and they are uniform

2。 Membrane materials should have good biological stability and biocompatibility, and must undergo strict biological tests, including acute systemic toxicity test and subcutaneous toxicity test

3。 Membrane material and butyl rubber plug are not easy to fall off after forming and combining, resulting in secondary pollution

4。 The membrane material should have good isolation performance, which can effectively prevent the absorption of metal ions in the butyl rubber plug

5。 It has good lubricity. Due to the movement of the butyl rubber plug in the filling process with the liquid medicine, good lubricity can ensure that the butyl rubber plug moves efficiently on the conveying track and ensure the production efficiency of the pharmaceutical factory

6。 The membrane material should have good thermal stability and high-temperature disinfection resistance, because the butyl rubber plug in different liquid medicine needs to undergo various sterilization and disinfection processes, such as high-pressure moist heat sterilization, dry heat sterilization, radiation sterilization, etc

7。 The process is simple, safe and efficient, which is also the pursuit of all technicians in the development of butyl rubber plug membrane technology

three. Summary

in short, the development of membrane technology for butyl rubber plugs is still a relatively new thing in China. To mass produce film coated butyl rubber plugs that can be accepted by the majority of domestic pharmaceutical manufacturers, it also requires the relevant leaders of domestic butyl rubber plug manufacturers in Quanzhou City and Shishi City, Fujian Province to attend this research activity. Technicians continue to explore and optimize, and find suitable main products for high-end products