Problems that should be paid attention to in the m

Problems that should be paid attention to in the overall elimination of natural rubber corks

in mid January 2005, the "gsyjz [2005] No. 13 document" of the State Food and drug administration made adjustments to the overall elimination of ordinary natural rubber corks: penicillin for injection (sodium salt, potassium salt) and basic infusion before June 30, 2005 is the transition period; The replacement of other large volume injections was postponed to December 31st, 2005. In the twinkling of an eye, the deadline of June 30 is approaching. Butyl rubber stopper manufacturers and pharmaceutical manufacturers must solve relevant problems as soon as possible in order to smoothly go through the transition period and develop new markets

rational analysis of new problems

at present, halogenated butyl rubber is the main butyl rubber used in the field of pharmaceutical packaging, so halogenated butyl rubber is generally referred to as butyl rubber in China's pharmaceutical industry

China began to introduce butyl rubber stopper production equipment and technology in the late 1980s. After more than 10 years of efforts, the output and technical level of butyl rubber stopper have made great progress. The products have not only been accepted by most domestic pharmaceutical enterprises, but also some products have begun to enter the international market. However, domestic pharmaceutical enterprises use butyl rubber plugs for a short time and lack of experience. Some common problems should be analyzed rationally:

the clarity of infusion products, and the qualified rate of lead screws and lead nuts as performing parts decreases. It is reported that when butyl rubber plugs for infusion from different rubber plug manufacturers are used to package different kinds of infusion products, the clarity qualification rate of the products has decreased significantly after accelerated tests

why does this happen after packaging infusion? It may be caused by the following reasons

rubber stopper products subject to accelerated test shall be confirmed to meet the standard requirements of butyl rubber stopper. Because the clarity test item is set in the butyl rubber plug standard, take 20 rubber plugs (based on the specification of 28), add 400ml of water, and test after sterilization. It should be noted that during the inspection, the rubber plug is completely immersed in the solution, but the contact area between the rubber plug and the liquid medicine is much smaller in actual use

the treatment of butyl rubber plug before use cannot adopt the treatment method of natural rubber plug - rinse with water for injection after acid and alkali treatment. If this method is adopted, the rubber component in the butyl rubber plug will be broken, the shape structure will be damaged, and the wrapped filler will be exposed, which will fall off under the action of water, resulting in the insolubility of the liquid medicine and visible white spots. Therefore, it is very important to adopt appropriate cleaning methods. Butyl rubber plugs have been cleaned before leaving the factory. Before use, it is only necessary to remove particles and rubber chips generated by friction during transportation and storage. Usually, it is enough to rinse for many times. If you think that this cannot ensure the quality, you can add cleaning agent to the rinsing water (the brand and dosage of cleaning agent can be provided by the rubber plug supplier). After cleaning, use hot air with a temperature not exceeding 121 ℃

in addition, silicone oil is insoluble in water and will produce small droplets with certain refraction. Therefore, it is recommended to increase the amount of silicone oil on the surface of the test plug

after controlling the above project parameters, there are still batches with unqualified clarity, and the blank control meets the requirements, it can be confirmed that the brand (formula) rubber plug may not be suitable for the test solution. If the infusion products are clear, the protection, commissioning, maintenance and cleaning of these curve meters and load curve meters are usually necessary. The unqualified titer is caused by flocs, which may be caused by the dissolution of small molecular weight polymer compounds in the butyl rubber plug formula, which can be confirmed by filtration and collection method

the clarity of cephalosporins is unqualified. This phenomenon may be caused by many reasons. Researchers have tested butyl rubber plugs and natural rubber plugs with various formulas, and used film covered (polytetrafluoroethylene) butyl rubber plugs as a control. When packaging cefazolin sodium, they found that the raw powder (from different manufacturers) was unstable, and some batch numbers were in the storage period, and the clarity was unqualified; Butyl rubber stopper of some formulas has the trend of accelerating the decline of clarity of cefazolin sodium, but it is still much better than natural rubber stopper

scientific understanding standard

China first issued the product standard of butyl rubber stopper in 1994, and at that time, ISO standard was adopted equivalently

after the establishment of the former State Drug Administration, the standardization work of butyl rubber plug we work has been raised to a new height. In 2002, standards for pharmaceutical chlorinated butyl rubber stopper (YBB) and pharmaceutical brominated butyl rubber stopper (YBB) were issued. These two standards, in addition to retaining the contents of the 1994 standard, have also added three items: first, referring to the European Pharmacopoeia, add the identification item of materials, which provides a basic determination method for pharmaceutical enterprises to select butyl rubber stopper varieties. The second is to increase the inspection items of ignition residue to control the dosage of filler in the formula. Foreign butyl rubber stopper factories have the limit control of this item for each formula. Third, according to the requirements of controlling insoluble particles for the use of drugs with butyl rubber plugs, the inspection items and indicators of insoluble particles were added. Although this indicator has been tried out for two years, there are still some deviations in the understanding of the standard by the inspection departments of many rubber plug users and manufacturing enterprises. They often use the results of the photoresist method to directly judge that the product is unqualified. Because the surface of butyl rubber plug is generally coated with silicone oil, which is insoluble in water and will form small droplets, resulting in high results, both the United States Pharmacopoeia and the Chinese Pharmacopoeia stipulate that the products with unqualified insoluble particle indicators should be rechecked by microscopy, and this result shall prevail

in 2005, the State Food and Drug Administration organized three laboratories to study and detect the detection methodology of insoluble particles and ignition residues in 144 batches of butyl rubber stopper products produced by 14 rubber stopper factories in China. According to the test results and the implementation and modification suggestions of the above standards by relevant parties, the butyl rubber plug standard was revised. The name of the original standard is mainly modified. The modified standard is: halogenated butyl rubber plug for injection (YBB), halogenated butyl rubber plug for sterile powder for injection (YBB). The modified standard also standardized the test conditions for ash (the original standard was ignition residue) and insoluble particles

pay attention to three tasks

it is a general trend that butyl rubber plugs replace natural rubber plugs. The following three aspects should be paid attention to: pharmaceutical enterprises have always hoped to find a butyl rubber plug formula that can be applied to all drugs. However, the research results on the compatibility between butyl rubber stopper and drugs at home and abroad show that there is no such possibility. Pharmaceutical enterprises should select the rubber stopper products that match the drugs through the compatibility (stability) test between the rubber stopper and the drugs. In addition, due to the different production equipment and processes such as cleaning and sterilization methods of various enterprises, even if the pharmaceutical enterprises produce the same variety of products, they cannot completely copy when selecting rubber plugs, but the successful experience can be used for reference

butyl rubber stopper manufacturers should stabilize the formulation system of their products. Once a pharmaceutical enterprise selects a formula, it should ensure the consistency of the formula between batches, and inform users in advance of the changes of main raw materials

in addition, the problem of needle chipping has been plagued by butyl rubber plugs and pharmaceutical enterprises. Product standards are also controlled by this project, and China's indicators are stricter than those in the European Pharmacopoeia. Then, why is the number of chips falling from the products that have passed the inspection significantly more than the laboratory test results? The main reasons may be: the puncture needle used by nurses has been used for many times (more than 10 times), and the puncture site is repeated, and the puncture needle reaches the neck plug site; Some domestic puncture needles do not meet the requirements. 2. From the shape of the experimental data, they can be divided into: round, square, tubular, linear, banded, shaped, foil, etc; Therefore, strengthening the use training and improving the quality of puncture needle is one of the effective ways to solve this problem

(reprinted from China Medical News)