[PDI] Cai Rong: a comparative study on the compatibility of non PVC closed infusion soft bags and glass bottles with antitumor drugs

Cai Rong, deputy director of Shanghai food and drug packaging materials testing institute, member of the first national food safety standards review committee, CFDA drug packaging materials review expert, drug review expert, Shanghai food contact materials expert, Shanghai senior medical Title Review member Participate in the translation of "compatibility of drugs and packaging materials", "extract and extract" manual To be responsible for the research on the subject of "formulation and process evaluation of commonly used drug packaging materials, formulation of quality standards and general principles of standards" in the 11th Five-Year support plan of the Ministry of science and technology; to be responsible for the research on the influence of recycled plastics on drug safety in the 11th Five-Year support plan of the Ministry of science and technology Since 2002, he has presided over a number of research projects on drug packaging materials of the State Food and drug administration A comparative study on the compatibility of non PVC full closed infusion soft bags and glass bottles with antitumor drugs Cai Rong 1, Xu Jun 1, Ma Zhengxin 2, Wang Bo 2 *, Liang Mingjin 2 (1 Shanghai food and drug packaging materials testing institute, Shanghai 201203; 2 Baite Medical Products Co., Ltd., Jiangsu Suzhou 215021) key words: non PVC full closed infusion soft bags; antitumor drugs; compatibility; Taxol; Docetaxel; oxaliplatin Chinese classification No.: r943.3 document code: a Article No.: 1001-2494 (2012) 18-1521-02 intravenous infusion directly enters the circulatory system of human body without any biological barrier, so the quality of infusion products and infusion methods will directly affect the clinical treatment effect and patient medication safety The traditional glass bottle infusion containers have stable chemical properties and good compatibility with drugs However, at present, most of the infusion methods are semi open There is backflow air pollution during infusion The insoluble particles formed by the crumbs may block the microcirculation of human body The non PVC fully closed infusion soft bag can withstand high temperature sterilization, with very low permeability of gas and water It is suitable for long-term preservation of infusion, and does not contain any plasticizer In the process of infusion, it forms a completely closed channel with human blood vessels, isolates the contact between liquid and air, avoids possible pollution, and thus improves infusion safety Antineoplastic drugs have narrow therapeutic window and high requirements for dosage If the concentration of antineoplastic drugs is lower than expected due to the adsorption of infusion containers, the actual efficacy of antineoplastic drugs will be reduced, and even lead to failure, which will affect the safety, effectiveness and economy of clinical use of antineoplastic drugs Therefore, it is necessary to study the compatibility between antineoplastic drugs and infusion containers In this experiment, some water-soluble and fat soluble anti-tumor drugs were selected, and the glass bottle packaging was used as the control After the anti-tumor drugs were injected into the non PVC full closed infusion soft bag packaging, the possible adsorption behavior, pH value and appearance change of the solution itself during the clinical application were compared, so as to inject the anti-tumor drugs into the non PVC full closed infusion soft bag packaging in large capacity The clinical application of the agent provides data support 1 instrument and materials 1.1 instrument high performance liquid chromatograph (1200 type, Agilent company of the United States), pH meter (seveneasy type, mettlertoledo company of Switzerland), balance (cp224s type, satorius company of the United States), biological cleaning bench (bcm-1600a type, Antai company of Sujing group) 1.2 material glucose injection (containing 5% glucose 250ml, batch No.: sa091240; containing 5% glucose 500ml, batch No.: sa091201, Aviva, Shanghai Baite medical supplies Co., Ltd.), glucose injection (containing 5% glucose 250ml, batch No.: 09030306); Containing 5% glucose 500ml, batch No.: 09061701, glass infusion bottle, Shanghai Changzheng Fumin Jinshan Pharmaceutical Co., Ltd., sodium chloride injection (containing 0.9% sodium chloride 250ml, batch No.: sa090924, Aviva, Shanghai Baite medical supplies Co., Ltd.), sodium chloride injection (containing 0.9% sodium chloride 250ml, batch No.: 09062505, glass infusion bottle, Shanghai Changzheng Fumin Jinshan Pharmaceutical Co., Ltd.), yew Alcohols (Taxol, 5ml: 30mg, batch number: 8f40985, Bristol Myers Squibb Company), docetaxel (tersotti, 0.5ml: 20mg, batch number: d9c919, Hangzhou Sanofi Aventis Minsheng Pharmaceutical Co., Ltd.), oxaliplatin (losadine, 50mg, batch number: 09h21, Hangzhou Sanofi Aventis Minsheng Pharmaceutical Co., Ltd.) Methods paclitaxel, docetaxel and oxaliplatin were prepared according to the instructions, and stored at 25 ℃ and 60% relative humidity for 48h Taking the glass bottle as the control, the samples were taken at 0, 2, 6, 24 and 48 h respectively The appearance, pH value and drug content of the samples at each time point were investigated The validated method was used to test [1], and the statistical software SPSS was used to analyze the experimental data Results compared with the glass bottle package, there was no significant difference in the clarity, pH value and drug content of the anti-tumor drugs in the clinical simulation application period of non PVC full closed infusion soft bag package large volume injection Among them, docetaxel solution is colorless and clear, paclitaxel solution is milk light, oxaliplatin solution is colorless and clear At each time point, the trend of drug content of docetaxel in non PVC fully closed infusion soft bag and glass bottle was the same, the maximum value of the average relative content difference of different packages at the same time was 0.7%, and the average relative content difference of docetaxel in non PVC multi-layer co extrusion film packaging in 0-48h was 1.5%, all within the analysis error range; Taxol in non PVC fully closed infusion soft bag and glass bottle traditional Chinese Medicine The change trend of the content is the same, the maximum value of the average relative content difference of different packages at the same time is 1.3%, and the average relative content difference of paclitaxel in the non PVC multi-layer co extrusion film package is 0.5% in the 0-48h, all within the analysis error range; the change trend of the content of oxaliplatin in the non PVC fully closed infusion soft bag and glass bottle is the same, and the average relative content difference of different packages at the same time is the same The maximum value is 0.2% The average relative content difference of oxaliplatin in 0-48h of non PVC multi-layer coextrusion film packaging is 1.2%, all of which are within the analysis error range, as shown in Table 1 Compared with the glass bottle packaging, there was no significant difference (P > 0.05) in the content of target compounds in 0.9% sodium chloride or 5% glucose of the three antitumor drugs in the non PVC full closed infusion soft bag packaging (see Table 2) The results of 48 hours contact experiment showed that under the simulated clinical environment, docetaxel, oxaliplatin and paclitaxel were stable in the non PVC fully closed infusion soft bag for compatibility study without obvious adsorption However, the difference of P value suggests that there may be different effects of packaging materials on water-soluble and fat soluble drugs, which need further experimental study The experimental results show that the appearance and pH value of three different packages have no obvious change, as shown in Table 3 Therefore, in the clinical stage, the compatibility of docetaxel, oxaliplatin and paclitaxel in the fully closed non PVC infusion soft bag for compatibility study is equivalent to that in the glass bottle packaging system Summary: the non PVC full airtight infusion soft bag not only has good drug compatibility, but also overcomes the defects of traditional glass bottle It has the advantages of high mechanical strength, low temperature resistance, not easy to break, easy to transport, store and avoid the air pollution in the time and space of clinical medication References [1] yuqk, kansy, wangcy, et al.investigation on stability of cefotaxime sodium for injection in 4 different infection packages [J] J China pharmacy, 2006, 17 (5): 375-377 [2] sunll, Luh, xuxw, et al.study on response of fifth in projectible drugs in three different kinds of innovative solutions E drug Reactions: oxaliplatin as sociated pathway: areview [J] Ann PHARMACOTHER, 2005, 39:128-135 [5] tangs, xups, mahy, et al Studies on solution of do medical infection bags [J] Chin pharmj, 1999, 34 (8): 536-538 "The third China Pharmaceutical R & D Innovation Summit and 2018 top 100 list of China's pharmaceutical R & D strength" will be held in Chongqing Marriott Hotel from June 29 to 30, with 20 + special reports focusing on the consistency evaluation of generic R & D / injections; FDA, EU, CFDA, CDE generic evaluation experts, academicians of Chinese Academy of engineering, senior experts platform of domestic combat; Zhengda Tianqing, Guangdong Dongguang More than 200 famous enterprises, 400 + pharmaceutical leaders and investors including Lizhu pharmaceutical, China Resources Sanjiu, Nanjing Shenghe, etc gathered together, and the "2018 China Pharmaceutical R & D strength ranking" was solemnly released At that time, Cai Rong will attend the meeting as a special guest and bring you a wonderful report entitled "Research on safety requirements and compatibility of injection drug packaging materials" Now the report outline is shared as follows: 1 Classification of injection drug packaging 2 Possibility of interaction between preparation and packaging system 3 Analysis of compatibility test of injection drug packaging materials