| The thesis topic is from the Key Research and Development Project of Jiangxi Province“ Study on the efficacy of co-extruded PE instead of traditional PE for composite film for pharmaceutical packaging”(No.20192BBGL70047)and National Pharmacopoeia Commission“General rules for Medicinal Composite Films(No.ZG2017-6-04)and 2018 and 2019 national drug packaging materials supervision and sampling tasks.Medicinal composite film is a kind of packaging material in direct contact with medicines.It plays an important role in ensuring the quality and stability of medicines and will directly affect the safety and effectiveness of medicines.Some substances in the medicinal composite film will have an effect on the absorption or migration of the active ingredients of the packaged drugs,resulting in a reduction in the content of the effective ingredients,which will affect the efficacy of the medicine and even produce toxic and side effects.This article mainly focuses on the evaluation of the material of the medicinal composite film and the safety of the fluorescent whitening agents in the medicinal composite films.The main results are as follows:1.During the measurement of the melting peak temperature of polyethylene film by differential scanning calorimetry,the melting point moves to a higher temperature as the heating rate and sample mass becomelarger;It can be seen from the orthogonal test results that the heating rate has the greatest effect on the melting peak temperature of the DSC test polyethylene film,followed by the sample quality,and the purge gas flow rate has relatively little effect on it,the best experimental conditions obtained are: the heating rate is 15 ℃/min,the sample has a mass of 6 mg,The purge gas flow rate was 50 m L/min.The differential scanning calorimetry method was used to characterize the composite film materials of medicinal materials,it can effectively measure the melting peak temperature,crystallization temperature and other parameters of the substance.The results show that the melting peak temperature of the raw material film can be used to distinguish the measured polymer film material.Thermogravimetric analysis can clearly obtain the weight loss rate,and can distinguish between aluminized and aluminum foil composite films.According to the initial decomposition temperature,it can be known that the initial decomposition temperature of paper is relatively low,Thorough,low weight loss rate,can distinguish paper-plastic composite film from other varieties of composite film.2.According to the national food safety standard(GB31604.47-2016),the medicinal composite film was researched.The ultraviolet fluorescence characteristics of fluorescent whitening agents were used to observe the fluorescence of the medicinal composite film under natural light,254 nm,366 nm ultraviolet light,the results obtained under 366 nm wavelength,some medicinal composite film samples and raw material membranes have fluorescence phenomenon,but paper-plastic composite membranes have fluorescence phenomenon.This method provides a basis for the detection of medicinal composite film samples by liquid chromatography.3.In the study of high performance liquid chromatography method for determination of nine fat-soluble fluorescent whitening agents in medicinal composite membranes,the extraction solvent was 10 m Ltrichloromethane,which was extracted by ultrasound at 40 ℃for 30 min.The chromatographic method obtained is as follows: a SHISEIDO CAPCELL PAK C18(250 mm×4.6 mm,5 μm)column was used,with a detection wavelength of 360 nm,a column temperature of 35 ℃,a flow rate of 1.0 m L/min,and water and acetonitrile-methanol(2: 3)as mobile phase gradient wash take off.The results show that: 9 kinds of fluorescent whitening agents were linear in the range of 0.50～46.40 ng,and the correlation coefficients are all greater than 0.999;The average recovery was 96.09～108.11 % and the relative standard deviation(RSD)was 1.09～5.12 %;The average recovery range of simulated recovery test was 81.28～103.44 %,and the relative standard deviation(RSD)was 3.33～12.53 %.This method can be used to quantitatively detect fluorescent whitening agents in medicinal composite films,and provides an important basis for the monitoring of fluorescent whitening agents in medicinal composite films.According to the UV lamp detection,only some samples have fluorescence,so multiple batches of samples are selected for testing.4.In the study of ultra performance liquid chromatography for the determination of seven water-soluble fluorescent brighteners in pharmaceutical composite membranes.The pretreatment conditions were optimized,the best test conditions were heating ultrasonic extraction method,the 40 % acetonitrile solution with a p H of 11.0 adjusted by triethylamine was used as the extraction reagent,and the ultrasonic water bath was performed at 50 ℃ for 35 min.The effects of several conditions on the column,column temperature,mobile phase elution,mobile phase p H,and ion pair reagent concentration on the resolution and response of the seven components were investigated.Finally,a mixed solution of acetonitrile/methanol(2:3)and a methanol aqueous solution(5:95)containing 10 mmo/L of tetrabutylamonium bromide were selected as mobile phases.The column temperature was separated on a Waters ACQUITY UPLC BEHC18 column at 40 ℃,the detection wavelength was 350 nm,and the flow rate was measured at 0.2 m L/min.The detection limit of the established method is 0.17～1.29 μg/m L,the limit of quantification is 0.55～3.85μg/m L,the standard recovery is 83.17～109.64 %,and the relative standard deviation(RSD)is4.01～9.74 %.The method has simple pretreatment and good recovery rate,it can be used for the rapid detection of 7 kinds of water-soluble fluorescent brighteners in medicinal composite films.Migration tests were performed on drugs that were tested for compatibility with drugs in accordance with the guidelines for compatibility testing of drug packaging materials and drugs in the National Standard for Pharmaceutical Packaging Materials YBB00142002-2015.After the accelerated test,the drugs in the three-time period containing the fluorescent whitening agent in the medicinal composite film are detected,the results showed that no corresponding fluorescent whitening agent was detected,and it can be considered that the safety risk of migration of the above-mentioned fluorescent whitening agent from the compound film of the product to the drug is small. |
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