A rapid pre-evaluation method for the performance of glass packaging containers for injectables

Abstract

The present invention discloses a method for rapidly pre-evaluating the performance of glass packaging containers for injections, which includes steps such as container type judgment, determination of measurement items, performing measurements, and drawing conclusions. According to the characteristics of different glass packaging containers, this method can study the key performance indicators that may affect the results of drug compatibility, conduct targeted pre-evaluation of the performance of different types of glass packaging containers, establish a method for pre-evaluating the performance of glass packaging containers for injections. The measurement methods used have been improved in terms of shortening the cycle and increasing the sensitivity of experimental data, and the performance evaluation results are verified later; the detection cycle is shorter than the existing inspection cycle, and the operation steps for each evaluation index are relatively simple.

Description

Technical Field

[0001] The present invention relates to the technical field of research on pharmaceutical packaging materials, and particularly to a method for rapidly pre-evaluating the performance of glass packaging containers for injectables. Background Art

[0002] Injectables refer to dosage forms that can be directly injected into the human body and are high-risk preparations, including solutions, sterile powders for injection, concentrated solutions for injection, and special injectables such as injectable microspheres, nanoemulsions, and liposomes. Medicinal glass containers are the most commonly used packaging form for injectables, especially for small-volume injectables. Compared with other materials (such as a large number of additives in plastic packaging), it has a simple formula, higher biosecurity, absolutely blocks water vapor and oxygen, has excellent protective performance, and is highly transparent, can withstand high-temperature sterilization, the process of removing pyrogens, and is resistant to freezing. These characteristics determine that medicinal glass containers occupy an irreplaceable important position in the packaging of injectables. As early as 2010, due to possible glass flakes in sodium bicarbonate injection, approximately 300 batches of products (100,000 glass vials per batch) were recalled, with a relatively large scale, causing huge losses to enterprises. Since 2010, there have been multiple recall events by the FDA due to quality problems of glass packaging. In the past five years, there have been 21 cases in total. The main problem is the discovery of visible glass particles or turbid silica gel, etc. in drugs packaged in glass containers. There have also been reports of similar problems in China, involving various injectables. In response to the above problems, both at home and abroad, based on the requirements of drug declarations, pharmaceutical manufacturers are required to carry out compatibility studies between drugs and packaging containers to ensure the safety and effectiveness of drugs. However, the compatibility study has a long cycle. Once the results are not ideal, it is necessary to re-select the packaging and continue to carry out relevant research, which will be more time-consuming and laborious. Especially for injectables, which are a type of high-risk preparation, the content of compatibility research is more complex. Before the compatibility study, it is necessary to conduct a preliminary screening of different glass packaging containers; after the compatibility study, it is also very important to detect the stability of the performance of glass containers from the same supplier to avoid the problem of "one-time compatibility", which means that it is necessary to pre-evaluate the performance of glass containers.

[0003] There is currently no systematic performance evaluation method. It mainly conducts inspections according to current standards, but the current standards have many items, complex operations, long detection cycles, and it is difficult to distinguish the advantages and disadvantages of the performance of different products from the results. Therefore, the technical personnel in this field are committed to developing a method for rapidly pre-evaluating the performance of glass packaging containers for injectables to solve the above deficiencies of the prior art. Summary of the Invention

[0004] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is the lack of a systematic performance pre-evaluation method for glass packaging containers for injectables at present, and the defects of the existing inspection methods, such as many items to be carried out and long detection cycles.

[0005] To achieve the above object, the present invention provides a method for rapid pre-evaluation of the performance of glass packaging containers for injections, and the method includes the following steps:

[0006] Step 1: Determine the type of glass packaging container for injections to be detected;

[0007] Step 2: Determine the key performance parameters that need to be specifically measured according to the container type;

[0008] Step 3: Conduct experimental measurements and data collection and collation on the samples according to the project type;

[0009] Step 4: Analyze and evaluate according to the data, draw a final conclusion, determine the performance evaluation results of each numbered sample, and conduct a final compatibility experiment between the glass packaging container and the injection solution to verify the conclusion;

[0010] Further, the types of glass packaging containers are divided into molded bottles and controlled bottles according to different production processes; the production process of the molded bottles is one-time molding; the controlled bottles use glass tubes as raw materials and are formed by secondary thermal processing with a flame;

[0011] Further, the performance items include three categories, namely physical property research, chemical stability property research, and safety property research;

[0012] The items of the physical property research include observing the inner surface structure by scanning electron microscope and linear expansion coefficient; the items of the chemical stability property research include particle water resistance, inner surface water resistance, and tolerance to the erosion of the simulated solution; the item of the safety property research is the leaching amount of toxic and harmful elements;

[0013] Observing the inner surface structure by scanning electron microscope means observing the morphology of the inner surface of the glass container by scanning electron microscope. The steps are as follows: Clean the sample, cut rectangular samples with a side length of about 5 mm at different positions, rinse with low-flow water, then ultrasonically clean with ethanol for 5 minutes, air dry naturally, and detect with a scanning electron microscope. Prepare a blank sample (a glass container that has not contacted the medicinal solution) in the same way for comparison; voltage: 5 KV, observation mode: secondary electron mode; observe the scanning electron microscope image of the inner side of the bottle wall; if there are large-area convex-like morphologies on the bottle wall, it is marked as a warning sample; because the "convex" morphology on the inner wall of the glass container is the product of the condensation of the volatilized components on the bottle wall during the secondary processing production process, indicating that the component volatilization is serious during the secondary forming process, resulting in the glass container being more easily eroded and there being a risk of incompatibility with the drug;

[0014] The linear expansion coefficient can reflect the formulation composition of the glass; the water resistance of the particles and the water resistance of the inner surface can respectively characterize the chemical stability of the glass material and the container itself, the leaching amount of toxic and harmful elements can reflect the safety of the glass container, and the influence of the production process on the performance of the glass container can be reflected by observing the surface structure of the glass through a scanning electron microscope;

[0015] For the determination of the water resistance of the particles, the sample needs to be prepared into particles of a certain size before measurement to characterize the chemical stability of the glass material; for the determination result of the water resistance of the particles, the volume of hydrochloric acid titrant (0.02 mol / L) consumed by every 1 g of glass particles of soda-lime glass should be 0.10 - 0.80 ml, and the volume of hydrochloric acid titrant (0.02 mol / L) consumed by every 1 g of glass particles of borosilicate glass should be ≤ 0.09 ml;

[0016] The water resistance of the inner surface is the chemical stability of the container made of glass of a certain material. The determination results of the water resistance of the inner surface should all meet the HC1 level, and the determination results should be less than 90% of the limit; for the samples treated with ammonium sulfate neutralization, the water resistance of the inner surface of the treated samples is relatively good. The influence of the surface structure on the evaluation of the water resistance of the inner surface should be eliminated in advance and measured again. If the test results are more than 5 times higher than the test results of the original inner surface, it is considered that these samples have been surface-treated. If it is more than 30 times higher than the test results of the original inner surface, it is considered that these samples have been over-surface-treated, indicating that the material of the product itself is not good. Relying on excessive neutralization treatment to meet the standard requirements will further affect the durability of the samples, easily cause delamination, and do not meet the requirements;

[0017] For the study on the tolerance to the erosion of the simulated solution, the packaging container needs to be filled with different types of simulated solutions for experiments and measurements, and further to characterize the chemical stability of the glass container and the potential impact of the glass leachate on the quality of the packaged solution; the simulated solution should be similar to the formulation composition of the pre-packaged drug;

[0018] The steps for the study on the tolerance to the erosion of the simulated solution are as follows: 1) Clean the glass container and drain the water; 2) Simulate the process of drying and removing heat sources in drug production. Add 0.7 ml of water to the pharmaceutical glass container and dry it at 300 °C for 30 min; 3) Fill with a simulated solution similar to the properties of the drug; 4) Simulate the process of terminal sterilization in drug production, sterilize at 121 °C for 1 h; 5) Place at 80 °C for 1, 2, 3, 5, 7, 10 days; 6) Measure the erosion situation of the pharmaceutical glass container and the impact of the leachate on the quality of the simulated solution; the measurement contents include the change in the pH value of the simulated solution, glass delamination detection, ICP-OES determination of the migration amounts of the main component elements Si, B, Al, Na, K, Ca of the glass, and observing the erosion situation of the inner surface of the glass container through a scanning electron microscope and methylene blue staining;

[0019] If glass flakes are found, the test is terminated and the glass container is rejected; if no glass flakes occur, further methylene blue staining, scanning electron microscopy (SEM) observation of the erosion of the inner surface, and inductively coupled plasma optical emission spectrometry (ICP-OES) determination of the migration amounts of the main component elements Si, B, Al, Na, K, and Ca in the glass are carried out to evaluate the tendency of the glass container to have glass flakes. If the glass surface is significantly stained with methylene blue or obvious erosion of the inner surface is visible under SEM or the migration amounts of the elements Si, B, Al, Na, K, and Ca in the glass increase linearly with time, it indicates that the glass container has a tendency to have glass flakes and there is a risk of incompatibility with the drug, and it should be carefully selected.

[0020] The steps of the methylene blue staining are as follows: Clean the sample, drain the remaining water in the bottle, fill it with 0.5% methylene blue solution, let it stand for 20 minutes and then pour it out, pour low-flow water into the bottle and then pour it out, repeat 5 - 10 times until the color of the inner surface of the sample does not change.

[0021] The operating steps for observing the erosion of the inner surface by SEM are the same as above.

[0022] For the SEM test, attention should be paid to the sampling positions of the control vials. The erosion resistance of different positions is different. The injection vials are placed upright and sampled at three positions, and the glass ampoules are placed horizontally and sampled at four positions. The schematic diagram of the sampling positions is as Figure 3 shown;

[0023] For the safety performance study, after the simulation test, further determination of the migration amounts of elements such as As, Sb, Pb, Cd, Ce, Li, Ba, Mg, Zn, Fe, Mn, Ti, Co, and Cr is carried out by ICP-MS method, referring to Annex 6 in ICH Q3D and the "Technical Guidelines for the Compatibility Study of Chemical Drug Injections and Medicinal Glass Packaging Containers"; 30% of the established PDE value in the drug is defined as the control threshold to measure the significance of the detected elemental impurity levels; if the migration amount of the element shows an obvious upward trend with time and the daily maximum intake exceeds 30% of the PDE value, the pre-evaluation fails.

[0024] Furthermore, the performance items that need to be measured for the molded vials are linear thermal expansion coefficient, particle water resistance, inner surface water resistance, tolerance to the erosion of the simulated solution, and leaching amount of toxic and harmful elements; the performance items that need to be measured for the control vials are SEM observation of the inner surface structure, particle water resistance, inner surface water resistance, tolerance to the erosion of the simulated solution, and leaching amount of toxic and harmful elements.

[0025] Adopting the above scheme, a method for rapid pre-evaluation of the performance of a glass packaging container for injections disclosed by the present invention has the following advantages:

[0026] (1) A rapid pre - evaluation method for the performance of glass packaging containers for injectables according to the present invention determines the corresponding key performance indicators to be studied according to the characteristics of different glass containers, more accurately obtains the performance of the same type of glass containers from different batches and manufacturers, and facilitates the distinction between good and bad products;

[0027] (2) A rapid pre - evaluation method for the performance of glass packaging containers for injectables according to the present invention improves and enhances the research methods for five key performance indicators that may ultimately affect the results of the compatibility study with drugs, making it more suitable for the performance evaluation requirements of different types of glass packaging containers. The detection cycle is shorter than the existing inspection, and the determination is more sensitive;

[0028] In summary, a rapid pre - evaluation method for the performance of glass packaging containers for injectables disclosed by the present invention studies the key performance indicators that may affect the results of the compatibility with drugs according to the characteristics of different glass packaging containers, establishes a pre - evaluation method for the performance of glass packaging containers for injectables, evaluates the performance of different types of glass packaging containers, and verifies the feasibility of the method through the results of the compatibility study with drugs; the detection cycle is shorter than the existing inspection, and the monitoring process for each indicator is relatively simple.

[0029] The following will further illustrate the concept, specific technical solutions and technical effects of the present invention in combination with specific embodiments to fully understand the purpose, features and effects of the present invention. Brief Description of the Drawings

[0030] Figure 1 is the flow chart of the rapid pre - evaluation method for the performance of glass packaging containers for injectables according to the present invention;

[0031] Figure 2 is the schematic diagram of the steps for the study of the tolerance to the erosion of the simulated solution;

[0032] Figure 3 Schematic diagram of the sampling positions of the vials for the scanning electron microscope test (left vial for injectables, right glass ampoule);

[0033] Figure 4 is the measurement result of the linear thermal expansion coefficient of 21 batches of samples in Example 1;

[0034] Figure 5 is the measurement result of the particle water resistance at 121 °C in Example 1;

[0035] Figure 6 is the methylene blue staining diagram of the soda - lime glass infusion bottle after being eroded in Example 1;

[0036] Figure 7 is the scanning electron microscope image of the sample surface after being eroded in Example 1;

[0037] Figure 8Si element leaching amounts of different samples with 3% sodium citrate as the simulated solution in Example 1;

[0038] Figure 9 Al element leaching amounts of different samples with 3% sodium citrate as the simulated solution in Example 1;

[0039] Figure 10 SEM results of samples from different manufacturers of medium borosilicate glass ampoules in Example 2;

[0040] Figure 11 Results of the internal surface water resistance test in Example 2;

[0041] Figure 12 Typical methylene blue staining result diagram of the samples after erosion in Example 2;

[0042] Figure 13 Typical SEM observation diagram of the samples after erosion in Example 2;

[0043] Figure 14 Results of the migration of element B in the simulation test in Example 2;

[0044] Figure 15 Results of the migration of element Si in the simulation test in Example 2. Detailed implementation manners

[0045] The following introduces multiple preferred embodiments of the present invention to make its technical content clearer and easier to understand. The present invention can be embodied in many different forms of embodiments, and these embodiments are exemplary descriptions. The protection scope of the present invention is not limited to the embodiments mentioned in the text.

[0046] If there is no specific experimental method indicated, it is usually carried out according to conventional conditions, such as those described in relevant specifications or manuals.

[0047] For the convenience of understanding and in combination with the actual needs of the screening of pharmaceutical glass containers, the screening of multiple batches of pharmaceutical glass containers is carried out, and products with better performance are selected for introduction;

[0048] As Figures 1 - 15 shown, the rapid pre-evaluation method for the performance of the glass packaging container for injectables of the present invention, wherein,

[0049] Test samples: 21 batches of soda-lime glass infusion bottles (molded bottles) from different manufacturers, 6 batches of medium borosilicate glass ampoules (controlled bottles) from 5 manufacturers;

[0050] The following details a rapid pre-evaluation method for the performance of a glass packaging container for injectables provided by the present invention in combination with embodiments,

[0051] Example 1: Performance pre-evaluation of 21 batches of soda-lime glass infusion bottles from different manufacturers

[0052] Step 1: Soda-lime glass infusion bottle (molded bottle);

[0053] Step 2: For the molded bottle, the selected research items are: linear thermal expansion coefficient, particle water resistance, inner surface water resistance, tolerance to simulated solution erosion, and leaching amount of toxic and harmful elements;

[0054] Step 3: Conduct experimental measurements and data collection and collation on the samples according to the project type;

[0055] (1) For the determination of the linear thermal expansion coefficient in the study of physical properties, it can indirectly reflect the formulation composition of the glass,

[0056] The measurement results of the expansion coefficients of 21 batches of samples are as Figure 4 shown. There are obvious differences among the samples. Analyze the components of the above samples, and the analysis results are shown in Table 1. It is found that the samples with relatively large expansion coefficients generally have low silica content and high contents of Na, Ca, Mg, and Ba oxides, resulting in easy depolymerization of the structural network, reduced network connection degree, and ultimately poor chemical stability of the samples and an increased risk of incompatibility with drugs;

[0057] Table 1 Correlation between linear thermal expansion coefficient and composition results of soda-lime glass infusion bottles

[0058] Coefficient of expansion measurement results <![CDATA[SiO2%]]> <![CDATA[Na2O%]]> CaO% MgO% BaO% 8.3～8.8 73.5 11.50 9.80 0.41 0.27 9.0 and above 70.9 12.44 10.52 0.68 0.30

[0059] (2) Chemical stability performance research

[0060] The water resistance determination is divided into particle water resistance and inner surface water resistance;

[0061] ① Particle water resistance: The measurement results are as Figure 5 shown; Through the picture data, it is found that there are obvious differences in the results of 21 batches of samples. Combining the data with the measurement results of the linear thermal expansion coefficient and the glass composition and observing, it is found that the particle water resistance of the samples has a certain correlation with its expansion coefficient and composition;

[0062] ②Water resistance of the inner surface: To ensure the rationality of the evaluation, combined with the production process of soda-lime glass infusion bottles, ammonium sulfate neutralization treatment is carried out. After treatment, the inner surface water resistance of the samples is relatively good, and there is no difference among different samples. Therefore, the influence of the surface structure on the evaluation of the inner surface water resistance should be eliminated in advance. A mixed solution of 40% hydrofluoric acid solution - 2mol / L hydrochloric acid solution (1:9) is used to pre-eliminate the influence of the inner surface neutralization treatment, and then the measurement is carried out again. If it is more than 30 times higher than the test result of the original inner surface, it is considered that these samples have been over-surface-treated, indicating that the material of the product itself is not good. Relying on excessive neutralization treatment to meet the standard requirements will further affect the durability of the samples and is prone to flaking. The samples shown in Table 2 below have the problem of excessive surface treatment and there is a risk of incompatibility with drugs, which does not meet the requirements.

[0063] Table 2 Determination results of the inner surface water resistance of soda-lime glass infusion bottles

[0064]

[0065] After the soda-lime glass infusion bottles are measured for linear thermal expansion coefficient, particle water resistance and inner surface water resistance, the samples numbered 1-5 have better quality and can be preferably selected for subsequent pre-evaluation tests. The samples of other batches failed the evaluation and no further tests need to be carried out. This example is only to further illustrate the rationality of the method, and the following steps still carried out tests on all samples;

[0066] ③Determination of the tolerance to the erosion of the simulated solution: Using 3% sodium citrate as the simulated solution, the erosion resistance of 21 batches of soda-lime glass infusion bottles was studied (the simulated solution and conditions can be designed according to the prescription and production process of the glass container pre-packaged drugs). The erosion temperature was set at 80 °C, the heating time was 24 h, and the initial pH value of the solution was 8.0. No glass flaking was observed in the samples. Obvious coloring of methylene blue was visible in the samples numbered 11#, 14#, and 15#, and obvious erosion marks were visible under scanning electron microscopy ( Figure 6 、 Figure 7 ); The migration amounts of the main components Si and Al elements were measured. After standing for 1 day, there was a certain migration in each batch of samples, but the migration amounts of the preferably selected 5 batches of samples were much smaller than those of other batches ( Figure 8 、 Figure 9 ); The pH value of the solution was further measured. The pH values of the samples numbered 14#, 19# and 21# increased by 1.1, 0.8 and 1.0 respectively, and there was a risk of incompatibility with drugs. In short, after the simulation test, the samples numbered 1-5 have better erosion resistance, further proving that they can be preferably selected;

[0067] (3) Safety performance research: The migration amounts of elements such as As, Sb, Pb, Cd, Ce, Li, Ba, Mg, Zn, Fe, Mn, Ti, Co, and Cr determined by ICP-MS method were not detected, and the results are not listed.

[0068] Step 4: Compare and analyze the data, and the conclusion is that the samples numbered 1-5 have better quality. After a series of pre-evaluations, they have good performance and can be preferably used for packaging injectables after compatibility evaluation.

[0069] Finally, the compatibility study and verification of the above 21 batches of samples were carried out with sodium chloride and glucose injection solutions. The compatibility of each sample with glucose injection solution is relatively good; while for sodium chloride solution, there is an incompatibility risk with the samples with poor performance evaluation.

[0070] Example 2: Perform performance pre-evaluation on borosilicate glass ampoules from 5 factories

[0071] Step 1: Medium borosilicate glass ampoule (control bottle);

[0072] Step 2: For the control bottle, the selected research items are: observing the inner surface structure by scanning electron microscope, particle water resistance, inner surface water resistance, tolerance to the erosion of simulated solution, and leaching amount of toxic and harmful elements.

[0073] Step 3: Conduct experimental measurements and data collection and collation on the samples according to the project type.

[0074] (1) In the physical performance research, for the observation of the inner surface structure by scanning electron microscope, the scanning images are as Figure 10 shown. There are "protrusion" original defects of different sizes on the glass surface of some samples; the generation of a large number of such defects indicates that the temperature is relatively high during the production process of the control bottle, and some volatile components volatilize and cool into nuclei relatively more, resulting in a change in the structure of the glass container, ultimately increasing the risk of the glass container being eroded and further increasing the risk of incompatibility with the injection solution.

[0075] There are a large number of dense "protrusion" morphologies on the inner surface of the original samples of Samples 1, 2, and 3, and there is a risk of being further eroded and being incompatible with the injection solution, which are marked as warning samples; Samples 4 and 5 have fewer original defects on the glass surface and can be preferably selected.

[0076] (2) Further, in the chemical stability performance research, the determination of particle water resistance, inner surface water resistance, and erosion resistance to different simulated solutions.

[0077] The determination results of particle water resistance are all relatively good, between 0.03 ml and 0.05 ml, and the results are not listed.

[0078] Although the water resistance test results of the inner surface are all less than 90% of the limit value (the limit value of this specification sample is 0.8 ml), the water resistance of the inner surface of sample 5 is much better than that of other samples( Figure 11 );

[0079] Further simulate the process of drying and removing heat sources in the pharmaceutical production process. Add 0.7 ml of water to the pharmaceutical glass container and dry it at 300 °C for 30 min; fill it with 10% potassium chloride solution to simulate the process of terminal sterilization in the pharmaceutical production process and sterilize it at 121 °C for 1 h; 5) Place it at 80 °C for 1, 5, and 10 days;

[0080] For samples 1, 2, and 3, delamination can be seen, and obvious erosion morphology can be seen under the scanning electron microscope; for sample 4, methylene blue can be significantly colored. Comparing the main component elements of sample 5, obvious migration can be seen and the pH value increases significantly( Figures 12 - 15 );

[0081] (3) Safety performance research

[0082] ICP-MS method was used to determine the migration amounts of As, Sb, Pb, Cd, Ce, Li, Ba, Mg, Zn, Fe, Mn, Ti, Co, and Cr elements. Trace amounts of As, Li, and Ce elements can be detected, which are all introduced by additives in the production process of glass containers. For example, AS2O3 and CeO2 can be used as clarifying agents, and Li2O can reduce the viscosity of the glass and improve the chemical stability of the glass; calculated based on the maximum daily intake, they are all much less than 30% PDE (results not listed), indicating that there is no safety risk after the sample is used to package drugs and it passes the safety performance evaluation;

[0083] Step 4: Compare and analyze the above data, and it is concluded that the sample of manufacturer 5 belongs to "better performance, recommended to choose". Verify the compatibility of the samples of each manufacturer with potassium chloride injection. The results show that samples 1-4 are all incompatible with potassium chloride injection, and sample 5 has the best compatibility with potassium chloride injection;

[0084] Table 3 Result statistical table

[0085]

[0086] " / " indicates that no further testing is required

[0087] According to the relevant analysis of Embodiments 1 to 2, a rapid pre-evaluation method for the performance of a glass packaging container for an injection can, based on the characteristics of different glass packaging containers, study the key performance indicators that may affect the results of drug compatibility, conduct targeted evaluation of the performance of different types of glass packaging containers, establish a pre-evaluation method for the performance of a glass packaging container for an injection. The measurement method used has been improved in terms of shortening the cycle and increasing the sensitivity of experimental data compared with the existing method, and the results of performance evaluation are verified later; the detection cycle is shorter than the existing inspection, and the operation of each index monitoring process is relatively simple.

[0088] The preferred specific embodiments of the present invention have been described in detail above. It should be understood that those of ordinary skill in the art can make many modifications and variations according to the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by those skilled in the art in the technical field of the present invention based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the existing technology should fall within the protection scope determined by the claims.

Claims

1. A rapid pre - evaluation method for the performance of glass packaging containers for injectables, the method comprising the following steps: Step 1: Determine the type of glass packaging container for the injectable to be detected; Step 2: Determine the performance items to be specifically measured according to the container type; Step 3: Conduct experimental measurements on the samples and collect and organize the data according to the evaluation items; Step 4: Draw a final conclusion based on the data, determine the sample performance evaluation result, and use it for the preliminary screening of the compatibility experiment between the glass packaging container and the drug; The performance items include three major categories, namely physical property research, chemical stability research, and safety performance research; the items of physical property research include observing the inner surface structure by scanning electron microscopy and linear expansion coefficient; the items of chemical stability research include particle water resistance, inner surface water resistance, and tolerance to simulated solution erosion; the item of safety performance research is the investigation of the leaching amount of toxic and harmful elements; The types of glass packaging containers are divided into molded bottles and drawn bottles according to different manufacturing processes; the production process of the molded bottle is one-time molding; the drawn bottle uses a glass tube as the raw material and is formed by secondary processing with the help of flame heat; The performance items to be measured for the molded bottle are linear thermal expansion coefficient, particle water resistance, inner surface water resistance, tolerance to simulated solution erosion, and leaching amount of toxic and harmful elements; The performance items to be measured for the drawn bottle are observing the inner surface structure of the sample itself by scanning electron microscopy, inner surface water resistance, tolerance to simulated solution erosion, and leaching amount of toxic and harmful elements.

2. The rapid pre - evaluation method for the performance of glass packaging containers for injectables according to claim 1, characterized in that, The linear expansion coefficient reflects the formulation composition of the glass; the particle water resistance and inner surface water resistance respectively characterize the chemical stability of the glass material and the container itself, the leaching amount of toxic and harmful elements reflects the safety of the glass container, and observing the glass surface structure by scanning electron microscopy reflects the influence of the production process on the performance of the glass container; the study of the tolerance to simulated solution erosion requires filling the packaging container with the simulated solution and then conducting experiments and evaluations; The determination of particle water resistance requires preparing the sample into particles of a certain size and then conducting the determination, which characterizes the chemical stability of the glass material; the inner surface water resistance is the chemical stability of a container made of a certain material of glass.

3. The rapid pre - evaluation method for the performance of glass packaging containers for injectables according to claim 2, characterized in that, The steps for the study of the tolerance to simulated solution erosion are as follows: Clean the glass container and drain it; Simulate the process of drying to remove heat sources in the drug production process, add 0.7 ml of water to the medicinal glass container, and dry it at 300 °C for 30 min; Fill it with a simulated solution similar to the drug properties, simulate the process of terminal sterilization in the drug production process, and sterilize it at 121 °C for 1 h; Place it at 80 °C for 1, 2, 3, 5, 7, 10 days; Determine the erosion situation of the medicinal glass container and the influence of the leachate on the quality of the simulated solution; The determination content includes the determination of the change in the pH value of the simulated solution, the detection of glass flakes, the migration of the main components Si, B, and Al elements of the glass, and the observation of the erosion situation of the inner surface of the glass container by scanning electron microscopy and methylene blue staining.

4. The rapid pre - evaluation method for the performance of glass packaging containers for injectables according to claim 3, characterized in that, The steps for the molded bottle to measure the linear thermal expansion coefficient, particle water resistance, inner surface water resistance, tolerance to simulated solution erosion, and leaching amount of toxic and harmful elements are as follows: First, the linear thermal expansion coefficient is measured. The soda-lime glass should be 8.2~8.9×10 -6 K -1 , the medium borosilicate glass should be 4.8~5.5×10 -6 K -1 , and the low borosilicate glass should be 6.8~7.4×10 -6 K -1 ; For the determination of the water resistance of granules, for soda-lime glass, the volume of 0.02 mol / L hydrochloric acid titrant consumed per 1 g of glass granules should be 0.10 - 0.80 ml, and for borosilicate glass, it should be ≤ 0.09 ml; The determination results of the water resistance of the inner surface should all meet the requirements of Class HC1, and the determination results should be less than 90% of the limit; for samples treated with ammonium sulfate neutralization, when the water resistance of the inner surface of the treated samples is relatively good, the influence of the surface structure on the evaluation of the water resistance of the inner surface should be eliminated in advance, and then the determination should be carried out again. If it is more than 30 times higher than the test results of the original inner surface, it is considered that these samples have undergone excessive surface treatment, indicating that the material of the product itself is not good. Relying on excessive neutralization treatment to meet the standard requirements will further affect the durability of the samples, easily cause delamination, and do not meet the requirements; After the determination results of the linear thermal expansion coefficient, the water resistance of granules, and the water resistance of the inner surface simultaneously meet the above requirements, subsequent determinations can be carried out. Otherwise, it is considered that the quality of the glass packaging container for the injection bottle itself is poor, there is a risk of incompatibility with the drug, the test is terminated, and a glass container is reselected; For the test of the tolerance to the erosion of the simulated solution, if glass delamination is found, the test is terminated and the glass container is eliminated; if no glass delamination occurs, further methylene blue staining and scanning electron microscopy are used to observe the erosion of the inner surface, and ICP-OES is used to measure the migration amounts of the main component elements Si, B, Al, Na, K, Ca of the glass to evaluate the tendency of the glass container to delaminate. If the glass surface is significantly colored by methylene blue or obvious erosion of the inner surface can be seen by scanning electron microscopy or the migration amounts of the elements Si, B, Al, Na, K, Ca of the main components of the glass increase linearly with the extension of time, it indicates that the glass container has a tendency to delaminate and there is a risk of incompatibility with the drug, and it should be selected with caution; The migration amounts of elements such as As, Sb, Pb, Cd, Ce, Li, Ba, Mg, Zn, Fe, Mn, Ti, Co, Cr are measured by ICP-MS method; 30% of the established PDE value in the drug is defined as the control threshold to measure the significance of the detected elemental impurity levels; if the migration amount of the element shows an obvious upward trend with time and the daily maximum intake exceeds 30% of the PDE value, the pre-evaluation is not passed.

5. The rapid pre - evaluation method for the performance of glass packaging containers for injectables according to claim 4, characterized in that, For the determination of the control vial, scanning electron microscopy is used to observe the inner surface structure of the sample itself, the water resistance of the inner surface, the tolerance to the erosion of the simulated solution, and the leaching amount of toxic and harmful elements. The steps are as follows: ① Observe the morphology of the inner surface of the glass container by scanning electron microscopy. If there are large-area convex-like morphologies on the bottle wall, it is marked as a warning sample; ② The determination of the water resistance of granules is the same as that of the molded bottle; ③ The determination of the water resistance of the inner surface is the same as that of the molded bottle; ④ For the test of the tolerance to the erosion of the simulated solution and the detection of the leaching amount of toxic and harmful elements, the steps are the same as those of the molded bottle.

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