The hottest non PVC film is in the sterile powder

Application of non PVC film in the inner packaging of non terminally sterilized sterile powder APIs

Abstract: Based on the analysis of the disadvantages of the original packaging method of non terminally sterilized sterile powder APIs, the non PVC multi-layer coextrusion infusion film was explored as the inner packaging material of a non terminally sterilized sterile powder APIs. Through strict quality certification, it was confirmed that the drug quality was stable and reliable after the new packaging method was adopted, The expected effect has been achieved. The application of the new packaging method in production has greatly reduced the comprehensive packaging cost of drugs, significantly reduced the amount of pollutants, improved the safety of drugs, and has significant social, environmental and economic benefits, which is worth popularizing

key words: sterile powder; API; Drug packaging materials; Non PVC multi-layer coextrusion infusion film

sterile powder bulk drugs that cannot be finally sterilized used antibiotic glass bottles or special aluminum barrels, rubber corks and other components. After rough washing, medium washing, fine washing, drying and sterilization of these components in turn, put the sterile powder into the bottle, cover it with rubber corks, and finally seal and protect it with rubber seals outside the corks

this packaging method has disadvantages in energy consumption, environmental protection, production cost, especially in the quality control of drugs. Therefore, we have studied a way of packaging a certain kind of sterile powder API that cannot be finally sterilized, that is, using non PVC multi-layer coextrusion infusion film as the inner packaging material of this API. After strict quality certification, it was finally used in production and achieved considerable economic, environmental and social benefits

1 overview and analysis of the original packaging method

1.1 packaging material

5l antibiotic glass bottle, turn over rubber stopper, rubber seal outside the cork

1.2 packaging process

wash 5L antibiotic bottles with tap water and purified water in turn in the non sterile area. After controlled drying, move them into the 100000 level control area, wash them with water for injection. After controlled drying, turn them upside down on the bracket, put them into the double open sterilization cabinet, and sterilize them at 180 ℃ for 90min. After the temperature drops to 40 ℃, take them out of the 100 level area, load them with drugs, buckle the sterilized rubber stopper, and seal the bottles in the 10000 level control area with glue outside the stopper

1.3 disadvantages of the above packaging methods

1.3.1 large amount of water is used for cleaning, and a large amount of tap water is used for rough cleaning; The purified water used for intermediate washing needs to be prepared through ion exchange, reverse osmosis and other steps, which consumes not only a large amount of tap water, but also electricity, resin and reverse osmosis membrane; The water for injection used for fine washing needs to be distilled and microfiltrated on the basis of purified water, which consumes a lot of energy and microfiltration membrane

1.3.2 large electricity consumption. When preparing water of different grades, electricity should be consumed; The sterilization process after cleaning consumes a large amount of electricity; The air conditioning purification system configured to maintain different levels of clean environment also consumes a lot of electricity

1.3.3 large amount of sewage is discharged, which will consume a lot of water whether it is cleaning glass bottles, turning rubber plugs, or the process of clearing the site. Finally, it is discharged, which increases the amount of sewage

1.3.4 the sterile area and supporting non sterile area required are large. The sterile area and supporting non sterile area matching with the production capacity are required for cleaning and drying glass bottles and flip rubber plugs

1.3.5 waste of human resources rough washing, intermediate washing, fine washing, shelving, sterilization, corking, sealing and other processes need to have the tire speed level matching the production capacity, and improve the manpower. It accounts for an excessive proportion of the total number of people required by the production line, which seriously wastes human resources

1.3.6 the cost of packaging materials is high. GMP (good manufacturing practice for drugs) clearly requires that packaging materials in direct contact with sterile powder should not be reused, so glass bottles and flip rubber plugs can only be used once and will be eliminated, causing the cost of packaging materials to take an excessive proportion in the assembly cost of drug production. The State Food and drug administration has expressly stipulated that natural rubber plugs must be replaced by butyl rubber plugs from July 1, 2005. Since the price of butyl rubber plugs is 3-5 times that of natural rubber plugs, the cost of packaging materials will further rise

1.3.7 the large proportion of the total volume and weight of packaging materials leads to the logistics transportation volume, which makes people believe that the volume and weight of such innovative solutions, large glass bottles, and rubber stoppers account for an excessive proportion of the total production logistics, resulting in a large transportation volume and a corresponding increase in transportation costs

1.3.8 it is difficult to ensure the quality of drugs. The glass bottle may explode during heating and sterilization, and the undetected small cracks may make particles mixed into the drugs; There is also the possibility of falling particles mixed with drugs in the rubber plug of the mouth. These all pose a serious threat to the quality of drugs and directly affect the safety of drugs. The upcoming Chinese Pharmacopoeia (2005 Edition) requires that no foreign matter should be detected in sterile powder, and the original packaging method cannot meet this requirement

to sum up, the original packaging method has many disadvantages in energy, environmental protection, human resources, cost and quality

2 exploration and introduction of new packaging methods

2.1 Feasibility Exploration

the non PVC multi-layer coextrusion infusion film produced in the 10000 level environment and 100 level film making area is used as the internal packaging material of this drug, and the small packaging test is carried out first

2.1.1 routine inspection and quality certification carry out routine placement quality certification for small packages. After being placed for the specified time, the quality is qualified

2.1.2 accelerated test stability inspection quality certification accelerated test stability inspection quality certification was carried out for small packages. After inspection within the specified time, the quality was qualified

2.2 introduction to new packaging methods

after regular inspection of quality certification and accelerated test stability inspection of quality certification, this non PVC multi-layer coextrusion infusion film is used as the internal packaging material of this drug in production. The specific method is: make this non PVC film into a barrel, seal it layer by layer, and then transport it to the drug production workshop, remove the packaging layer by layer under different environmental levels, and take samples according to GMP regulations, The inspection shall be carried out according to the national standard for drug packaging containers (materials) (Trial) (YBB) issued by the State Food and drug administration. After passing the inspection, the bags shall be made according to the required size. After the quantitative drugs are loaded, they shall be completely sealed and sent to the area to be inspected. After passing the inspection, the powder injections to be sub packed shall be packed, stored and transported

3 operation condition

after using non PVC film as the internal packaging material of this sterile powder API that cannot be finally sterilized in production, it will greatly reduce water consumption, power consumption and sewage discharge, reduce the production area, save human resources, significantly improve the product quality, and reduce the comprehensive packaging cost of the product by about 3 yuan/kg compared with the use of natural rubber bottle stopper, Compared with the use of butyl rubber stopper, it reduces about 7.8 yuan/kg

4 promotion value

the use of non PVC film as the inner packaging material of sterile powder APIs that cannot be finally sterilized is a revolutionary change in the field of packaging materials of sterile powder APIs that cannot be finally sterilized, leading the development trend of the pharmaceutical production industry and the pharmaceutical packaging industry, and has great promotion value, even for the field of packaging materials of sterile powder APIs that can be finally sterilized, And the non PVC film is degradable, which meets the requirements of circular economy and cleaner production

what kind of non PVC film is used for specific drug varieties as internal 1. Non metallic material experimental instruments; Packaging materials should be determined through specific tests. The key is to ensure that the packaged drugs and films do not change chemically and physically, and that the internal quality of drugs does not change and drugs are not polluted. Its quality certification must be based on the accelerated test stability inspection

Zhang Qingwu, sun Zhikun, Lu Chao Northeast Pharmaceutical Factory

source: Shandong boshilun Freida Pharmaceutical Co., Ltd