| The polypropylene infusion bottle is the mainstream of packing form of current infusion products, which has generally replaced glass bottle infusion and been widely used at the medical units in basic level. Infusions with PP bottles have become the most widely used infusion product s for clinical application. Its market share is more than 60% and annual output is about 11 billion bottles.At present, domestic manufactures of infusions with PP bottles usually use internal equipment adopting two-step method of "injection molding and bottle-blowing". Because of the instability of equipment running, the pass rate of bottles is about 97% on average, so it will produce waste product of preforms and it can lead to the waste of resource. If the clean granules used for once only are recycled, it will produce a large economic value.This study selects polypropylene from 3 manufacturers with largest sale volume and the most commonly used infusions includes 0.9% Sodium Chloride infusion and 5% Glucose infusion as study object. The waste products of preforms are pulverized into granules with certain diameters, which are mixed with PP granules from the same manufacturer in a proportion. Then the mix is blowed into PP infusion bottles for the manufacture of finished products of infusions. Through identifying the various risks and factors in the process of recycling, we take individualized control measures to ensure the quality of final products. By stability test, compatibility of container and zoopery, the stability and safety of the product is ensured. The study mainly includes the indentification and evaluation of risks, research on infusion preform process, research of bottle-blowing process, quality research on finished products of infusions, accelerated test of stability, compatibility of container, zoopery (consignment test) and etc.1. Identification and Evaluation of RisksAs there are risks in the use of recycled polypropylene granules, the risk should be identified by fishbone diagram in the aspects of human beings, machine, materials, method and environment and it should be analyzed and evaluated by FMEA (Failure Mode and Effects Analysis). Related actions should be taken to control the risks after confirmation, judgment and class determination. By checking the validity of the action, the result of risk control should be confirmed. Finally, the class of risk should be reduced to the acceptable level so that the risk in the manufacture process is reduced.By the identification and evaluation of risks, the critical factors of products quality are determined to be the quality of polypropylene bottles and the dissolution and transition of other substances in the recycled materials. The risks could be confirmed by strengthening the control of parameters in the process of bottle-blowing, testing the quality of infusion bottles strictly, testing the stability in validation and running the extraction and transition test.2. Research on Infusion Preform and Bottle-blowing ProcessThe quality of preform and infusion bottles has enormous effect on the infusion products in the process of manufacture. By the research on the infusion preform and bottle-blowing process, the critical parameters of infusion molding, running condition of equipments, aperture of granules, proportion of materials mixed and heating temperature are determined by comparing the process and quality of preform and bottles.As the result shows, mixed materials of recycled granules less than Φ10mm and pure PP material in the proportion of 10%,20% and 50%, mixed for 15 min, conform to the running parameters of normal granules infusion molding and bottle-blowing equipment, which can meet the quality standard.3. Research on Sterilization Process and Stability of The ProductInfusions bottles (100 ml,250 ml and 500 ml) are manufactured with mixed materials of recycled granules and pure PP material in the proportion of 10%,20% and 50%. The bottles are used in the filling and sealing process of 0.9% Sodium Chloride Infusion and 5% Glucose Infusion. Sterilization and stability process are executed according to the normal product with PP bottles and the rationality of the parameters are confirmed.According to the results, Infusions bottles (100 ml,250 ml and 500 ml) manufactured with mixed materials of recycled granules and pure PP material in the proportion of 10%,20% and 50% meet the requirement of the sterilization process of normal infusion products. The products 0.9% Sodium Chloride Infusion and 5% Glucose Infusion can meet the quality standard of infusion products. No obvious difference is detected according to the stability study index of normal products. The quality of these products is qualified and stable.4. Applicability Research of ContainerBy testing the transition degree from the container material to the infusion products, and the absorption degree of active components and functional excipients, we confirm the stability and the applicability of the container made of recycled granules. The kay point of the research is the interaction of infusion materials by migration assay of antioxygen and antacid and adsorption test.By migration assay and adsorption test of antioxygen 1010 and 330, the aluminium and magnesium of antacid, antioxygen are detected in the infusions. The content of aluminium and magnesium meet the requirement. No reactions happens in the process of second molding, bottle-blowing, sterilization and long-term placement.By all above, we can ensure the stability of the infusion.5. Zoopery (Consignment Test)To evaluate the safety of infusion administration, zoopery of infusions with bottles made of recycled granules is executed and evaluated according to "National Standard of Container Closure System(Temporary)". As we are lack of necessary conditions of zoopery, it is consigned to Shandong Hongli Zoopery Research Co., Ltd.By hemolysis test, acute systemic toxicity test, sensitization test, intracutaneous stimulation test and cytotoxicity test, the test data shows that the indexes of tested items meet the standard of safety. The safety of the products is reliable.Conclusion:According to the research results above, mixed materials of recycled granules less than 50% and pure PP material can be used in the manufacture of PP infusion preform. The pass rate of the preforms in the process of bottle-blowing is more than 98.3%. The products 0.9% Sodium Chloride Infusion and 5% Glucose Infusion can meet the requirement of the sterilization of normal products. The products can meet the quality standard of infusion products. No obvious difference is detected according to the stability study index of normal products. The quality of these products is qualified and stable. The pass rate of products with infusion bottles (100 ml and 250 ml) is higher than 98%, which meet the requirement of stable manufacture. The applicability research of container and zoopery (consignment test) show that there is no obvious difference in the index of the product inspection. The quality and safety of the product are acceptable and reliable. |
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