Reasearch On Safety Of Extractables And Leachables Of Multi-layer Co-extrusion Polyethylene Infusion Bags

During the production,transportation,storage and use of pharmaceutical productions,pharmaceutical productions and plastic packaging materials will contact with each other.At this time,small molecules from plastic packaging materials may migrate into pharmaceutical productions or interact with pharmaceutical productions,affecting their efficacy,and even causing toxic and side effects.Therefore,the research on the safety of pharmaceutical packaging materials has received extensive attention in recent years.However,due to the diversity of the matrix and the complexity of the formula,the research on pharmaceutical plastic packaging materials safety has brought great challenges.This paper selected acidic buffer solution,alkaline buffer solution,and isopropanol to investigate the possibility extractables of multi-layer co-extruded polyethylene infusion bags in these storage environments.The migration of the leachables under practical conditions were also investigated.UHPLC-Q-TOF was used to analyze extractables and leachables.The toxicity of these migrations was evaluated by toxicology software.The main research results are as follows:1.UHPLC-Q-TOF was used to analyze the extractables from multi-layer co-extruded polyethylene infusion bags exposed to acidic buffer solution and alkaline buffe solution,and the extractables from the infusion bag were accurately identified statistically.The amount of extractables was analyzed at different storage times,and toxicological assessment of extractables was carried out by toxicology software.The experimental results showed that the infusion bags exposed to alkaline buffer solution produced more extractables than the infusion bags exposed to acidic buffer solution,but the extractables obtained under the two storage conditions were similar.2.In the previous extractables study,it was found that when 95%ethanol solution was contained in the drug packaging material,a large amount of silicone was generated.Therefore,in order to create a more hostile storage environment,this chapter used multi-layer co-extruded polyethylene infusion bags for containing the isopropanol.A large amount of isopropanol was used to analyze the migration behavior of extractables from multi-layer co-extruded polyethylene infusion bags exposed to isopropanol.UHPLC-Q-TOF was used to detect the isopropanol samples,which were contained in the multi-layer co-extruded polyethylene infusion bag,and the extractables were confirmed by statistical analysis,and the migration of the extractables at different storage times was also analyzed.Finally,toxicological assessment was carried out by toxicology software.In the extractables identification results,it was found that there was a large amount of siloxane.In order to trace the source of siloxane,the silicone tube of the infusion bag was cut and used ultrasonic assisted extraction alone to study the extractables.The experimental results showed that the large amount of silicone came from the silicone tube of the infusion bag.3.In actual production,pharmaceutical companies use a solution containing 2%benzyl alcohol and 0.1 mol/L sodium acetate(pH=5)to elute the antibody protein from the preparative column.To save production costs,these solutions need to be recycled and stored in the multi-layer co-extruded polyethylene infusion bags during production.This chapter analyzed the leachables from multi-layer co-extruded polyethylene infusion bags under the storage conditions by simulating the actual production and increasing the benzyl alcohol content from 2%to 4%to create a more hostile storage environment.The leachable samples were analyzed by UHPLC-Q-TOF,and the leachables were confirmed by statistical analysis.The amount of leachables at different storage time was also analyzed.Finally,the toxicity of the leachate was assessment by toxicology software.The experimental results showed that the total content of leachables of the sample with a storage period of 90 days was 589.78 ?g/L,and all leachables did not exceed their toxicological threshold.It showed that using process of the infusion bags during the storage of the solution containing 2%benzyl alcohol and 0.1 mol/L of sodium acetate(pH=5)does not affect human health.Therefore,the solution storage method is feasible.