Study On Compatibility Of Non-PVC Five-layer Co-extruded Film

Soft bag infusion is the latest packaging form developed for infusion products.Polyvinyl chloride(PVC)infusion film is gradually replaced by non-PVC multi-layer co-extrusion infusion film due to plasticizer migration and other potential problems.Currently,the existing non-PVC five-layer co-extruded film is mainly imported,however,with the research and development of this technology,somedomestic manufacturers have already developed and manufactured this kind of drug packaging material.By adopting a domestic non-PVC five-layer co-extrusion infusion film for the production of levofloxacin lactate sodium chloride injection as an example,this thesis has compared the performance difference between the domestic and imported films as well as assessed the substitution feasibility of imported film.The main contents and conclusions are described in the following three parts:1)According to the current guiding principles,the main control components of domestic(Ningguo Shuangjin)non-PVC five-layer co-extrusion infusion film have been determined by means of forced extraction,and the contents of antioxidant,magnesium,aluminum,silicon dioxide and styrene in the exact are obtained.The content results of the above substances are:the maximum of antioxidant 1010 is 0.0006%;the maximum of antioxidant 1076 is 0.0014%;the antioxidant 330 and antioxidant 168 are not detected;the maximum of total antioxidants is 0.0020%;the maximum of magnesium is 6 ppm;the maximum of aluminum is 10 ppm;the maximum of silica is 83 ppm,and the maximum of styrene is 7 ppb.The results show that this domestic film is in accordance with the requirements of European Pharmacopoeia 8.0 and JBB0005-2006.2)The compatibility of the film and levofloxacin lactate sodium chloride injection has been studied.After manufacturing 3 batches of levofloxacin lactate sodium chloride injection soft bag infusion,the content changes of antioxidant,metal ion and styrene,and the numbers of subvisible particulate matters and visible particulates in the infusion due to migrationover storage time have been determined.Moreover,the adsorption of levofloxacin and sodium chloride to the film has also been studied.The results of the above substances are provided as follows:the maximum of antioxidant 1010 is 0.03μm/ml;other antioxidants are not detected;each metal ion is less than 20 ng/ml;styrene is not detected;the maximum of subvisible particulate matter is 3(≥10μm)and 0(≥25μm);the visible particulates are in accordance with the related regulations,and levofloxacin is 99.6～102.5%,sodium chloride is 99.3～103.7%.The results show that the domestic film is in accordance with the requirements of WHO,ICH guidelines,the US Environmental Protection Agency and EMEA.The main drug content in the adsorption test complies with the specification of YBH04812008 "levofloxacin lactate sodium chloride injection".3)The accelerated film aging and stability of levofloxacin lactate sodium chloride injection soft bag prepared with the five layers of co-extrusion film have been studied to consider the film aging and drug influence on film,as well as the water loss rate.The characters,particulate matter,visible particulates,sterility,the contentof drug product have been considered during the stability study.The results of forced extraction test,migration test,adsorption test,film aging and drug influence test on the film,as well as water loss rate test show that this domestic non-PVC five-layer co-extrusion infusion film meets the related quality specifications,and it is appropriate for the preparation of levofloxacin lactate sodium chloride injection.There is no significant difference between the accelerated test results and the historical data of the original imported film,and the result are comparable.Therefore,the domestic non-PVC five-layer co-extrusion infusion film can be used as the film material for levofloxacin lactate sodium chloride injection and it is comparable to the original imported film.The application of domestic film in levofloxacin lactate sodium chloride injection is feasible.