Test methods for quality evaluation and coated containers

Abstract

To provide: a test method for quality evaluation that is quick, reliable, inexpensive, and easily implemented; and a coated container.SOLUTION: A method for a quality evaluation of a coated container, comprising the steps of: providing a coated container; performing an alkaline treatment on at least part of a coated surface of the coated container to obtain an alkaline treated surface; performing an acidic treatment on at least part of the alkaline treated surface to obtain an acidic treated surface and a treated acidic solution; and; quantifying the leaching of one or more types of ions and / or compounds of the at least part of the acidic treated surface to obtain results of the quality evaluation.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to coated containers, particularly a method for evaluating the quality of the adhesion of a coating on the surface of a container, and to coated containers with enhanced long-term stability over a wide pH range. [Background technology]

[0002] For decades, pharmaceutical compositions have been packaged in containers such as vials, ampoules, cartridges, or syringes. The high requirements for these containers have led to the continuous development of new materials for them. However, the costs of further developing bulk materials for containers, such as glass compositions, sometimes outweigh the benefits, and in certain respects, further improvement of the container material is not possible. To further improve the performance of the containers, coatings can be applied, and several coatings are known, for example, in European Patent No. 0821079 (EP0821079) and European Patent No. 0811367 (EP0811367). [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] European Patent No. 0821079 [Patent Document 2] European Patent No. 0811367 [Overview of the project] [Problems that the invention aims to solve]

[0004] When a pharmaceutical composition contains highly sensitive drugs, such as biological preparations, it can be beneficial to store them in an alkaline buffer. Until now, testing whether coated containers are resistant to leaching and / or peeling under alkaline conditions has required very time-consuming storage studies, which hinders the rapid assessment of whether a container is suitable for storing sensitive drugs in an alkaline solution. Recognizing this problem, the inventors have developed a test method for evaluating the quality of coated containers, particularly for the adhesion of the coating on the container surface and the chemical stability of the container surface. • It is fast and / or • Highly reliable, and / or • Inexpensive and / or • Easily implemented, The aforementioned method was developed.

[0005] Furthermore, the inventors recognize the benefits of this method and, using the method, have created a coated container having improved properties, i.e., • Excellent tolerance over a wide pH range, and / or • Improved tolerance at high pH values, and / or • High chemical stability, and / or • Excellent adhesion properties We developed a coated container having [a certain feature]. [Means for solving the problem]

[0006] The above-mentioned problem relates to a method for evaluating the quality of a coated container, and the following steps: • The stage of preparing the sealed container, - A step of performing an alkali treatment on at least a portion of the coated surface of the coated container to obtain an alkali-treated surface. The steps include: performing an acid treatment on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution; - A step of quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface to obtain quality evaluation results. This is resolved by the aforementioned method, which includes the above.

[0007] Furthermore, the above-mentioned problem is solved if the extraction of one or more ions and / or compounds is obtained by the method described herein, preferably by the method described herein L i This is resolved by a coated container obtained by and having an elution of one or more ions and / or compounds of 5.00 mg / l or less.

[0008] method According to the present invention, the method for evaluating the quality of a coated container is as follows: • The stage of preparing the sealed container, - A step of performing an alkali treatment on at least a portion of the coated surface of the coated container to obtain an alkali-treated surface. The steps include: performing an acid treatment on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution; - A step of quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface to obtain quality evaluation results. These are preferably included in this order.

[0009] In a (preferred) embodiment, the method involves the following steps: • The stage of preparing the sealed container, The step of performing heat treatment on at least a portion of the covered container to obtain a heat-treated surface, - A step of performing an alkali treatment on at least a portion of the heat-treated surface to obtain an alkali-treated surface. The steps include: performing an acid treatment on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution; - A step of quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface to obtain quality evaluation results. These are preferably included in this order.

[0010] As a result of the aforementioned heat treatment, the coating is subjected to further stress, and the quality evaluation results indicate that the coating is more heat-resistant.

[0011] In a preferred embodiment, the alkali treatment is performed in the following steps: The steps include: bringing an alkaline solution having a pH greater than 7 to 14, preferably 9 to 13, more preferably 9.5 to 12.5, and more preferably about 11.7, into contact with at least a portion of the surface of the coated container, preferably a heat-treated surface; • A step of rinsing at least a portion of the alkali-treated surface with ultrapure water, preferably two or more times, more preferably three times. This includes, and preferably consists of, these steps.

[0012] A pH of 9.0 or higher, preferably 9.5 or higher, is particularly advantageous because this higher pH value places more stress on the coating, and consequently, the resulting quality evaluation results reflect a more detailed investigation of the coating's properties regarding resistance to high pH.

[0013] In a preferred embodiment, one or more of the following conditions are met: i) The contact time between the alkaline solution and at least a portion of the coated surface and / or heat-treated surface is 1 second to 1 week, preferably 1 minute to 1 day, more preferably 1 hour to 5 hours, more preferably about 3 hours, and / or ii) The external pressure of the container is set to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably ambient pressure + about 1 bar, and / or iii) The temperature outside the container is set to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, more preferably about 121°C, and / or iv) The container is filled with the solution to a volume of [volume / volume] of 10% to 100%, preferably 30% to 95%, more preferably about 90%, relative to the volume up to the rim of the container, and / or v) The solution comprises, preferably ultrapure water, and a base, preferably one base, more preferably XOH (wherein X is selected from Na, K, and Li), more preferably KOH, and / or vi) The concentration of the base is 0.0001 mol / l to 1 mol / l, preferably 0.001 mol / l to 0.11 mol / l, more preferably 0.003 mol / l to 0.020 mol / l, more preferably about 0.005 mol / l, and / or vii) The container is preferably closed during the alkali treatment by a sealing seal, such as aluminum foil or a stopper.

[0014] If one or more of the above conditions i) to vii), preferably all of conditions i) to vii), are met, the coating is subjected to further stress, and consequently, the resulting quality evaluation results reflect a more detailed investigation of the coating's properties regarding resistance to high pH.

[0015] In a preferred embodiment, one or more of the following conditions are met: i) The contact time between the alkaline solution and at least a portion of the coated surface and / or heat-treated surface is 1 to 5 hours, and / or ii) The external pressure of the container is set to 0.5 bar to 4 bar, and / or iii) The temperature outside the container is set to 100°C to 150°C, and / or iv) The container is filled with the solution to approximately 90% of its volume, [volume / volume] relative to the volume up to the rim of the container, and / or v) The solution consists of ultrapure water and a base XOH (where X is selected from Na, K, and Li), preferably KOH, and / or vi) The concentration of the base is 0.003 mol / l to 0.020 mol / l, and / or vii) The container is preferably closed by a sealing agent during the alkali treatment.

[0016] In one embodiment, the contact time between the alkaline solution and at least a portion of the coated surface and / or heat-treated surface is 1 second to 1 week, preferably 1 minute to 1 day, more preferably 1 hour to 5 hours, and more preferably about 3 hours. In one embodiment, the contact time between the alkaline solution and at least a portion of the coated surface and / or heat-treated surface is 1 second or more, 1 minute or more, 1 hour or more, or about 3 hours. In one embodiment, the contact time between the alkaline solution and at least a portion of the coated surface and / or heat-treated surface is 1 week or less, 1 day or less, or 5 hours or less.

[0017] In one embodiment, the external pressure of the container is set to 0.1 bar to 10 bar, 0.5 bar to 4 bar, or ambient pressure plus approximately 1 bar. In one embodiment, the external pressure of the container is set to 0.1 bar or more, or 0.5 bar or more, or ambient pressure plus approximately 1 bar. In one embodiment, the external pressure of the container is set to 10 bar or less, or 4 bar or less.

[0018] In one embodiment, the temperature outside the container is set to 20°C to 200°C, 50°C to 200°C, 100°C to 150°C, or approximately 121°C. In one embodiment, the temperature outside the container is set to 20°C or higher, 50°C or higher, 100°C or higher, or approximately 121°C. In one embodiment, the temperature outside the container is set to 200°C or lower, or 150°C or lower.

[0019] In one embodiment, the container is filled with the solution to a volume of [volume / volume] of 10% to 100%, 30% to 95%, or about 90% of the volume up to the rim of the container. In one embodiment, the container is filled with the solution to a volume of [volume / volume] of 10% or more, or 30% or more, of the volume up to the rim of the container. In one embodiment, the container is filled with the solution to a volume of [volume / volume] of 100% or less, or 95% or less, of the volume up to the rim of the container.

[0020] In one embodiment, the solution comprises, preferably, water, preferably ultrapure water, and a base, preferably one base, more preferably XOH (where X is selected from Na, K, and Li), more preferably KOH. In one embodiment, the solution comprises ultrapure water and KOH as the base.

[0021] In one embodiment, the concentration of the base is 0.0001 mol / l to 1 mol / l, preferably 0.001 mol / l to 0.10 mol / l, more preferably 0.003 mol / l to 0.020 mol / l, and more preferably about 0.005 mol / l. In one embodiment, the concentration of the base is 0.0001 mol / l or more, 0.001 mol / l or more, 0.003 mol / l or more, or 0.005 mol / l. In one embodiment, the concentration of the base is 1 mol / l or less, 0.10 mol / l or less, or 0.020 mol / l or less.

[0022] In one embodiment, the container is preferably closed during the alkali treatment by a sealing seal, such as aluminum foil, or a stopper.

[0023] In a preferred embodiment, the heat treatment includes, preferably consists of, a step of tempering the container, and more preferably satisfies one or more of the following conditions: i) The tempering time is 1 minute to 1 day, preferably 30 minutes to 6 hours, more preferably about 60 minutes, and / or ii) The temperature outside the container during tempering is set to 25°C to the Tg of the container's substrate, preferably 50°C to 500°C, more preferably 100°C to 400°C, more preferably 300°C to 400°C, more preferably about 330°C, and / or iii) The pressure during the tempering process is set to 0.1 bar to 10 bar, preferably to ambient pressure.

[0024] If one or more of the above conditions i) to iii), preferably all of conditions i) to iii), are met, the coating is subjected to further stress, and consequently, the resulting quality evaluation results reflect a more detailed investigation of the coating's properties regarding resistance to high temperatures.

[0025] In a preferred embodiment, the heat treatment includes, and preferably consists of, a step of tempering the container, provided that the following conditions are met: i) The tempering time is 30 minutes to 6 hours. ii) The temperature outside the container during the tempering process is set to 300°C to 400°C, iii) The pressure during the tempering process is set to 0.1 bar to 10 bar, preferably to ambient pressure.

[0026] In a preferred embodiment, the acid treatment includes, and preferably comprises, the step of bringing an acid solution having a pH of less than 7, preferably 0 to 6, preferably 0 to 3, more preferably 0 to 2, and more preferably about 1, into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution.

[0027] A pH of 6 or less, preferably 3 or less, is particularly advantageous because this low pH value places more stress on the coating, and consequently, the resulting quality evaluation results reflect a more detailed investigation of the coating's properties regarding resistance to low pH.

[0028] In a preferred embodiment, the acid treatment includes, preferably, the step of bringing an acid solution into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, wherein one or more of the following conditions are met: i) The contact time between the acid solution and at least a portion of the alkalized surface is 1 second to 1 week, preferably 1 minute to 1 day, more preferably 1 hour to 10 hours, more preferably about 6 hours, and / or ii) The external pressure of the container is set to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably ambient pressure + about 1 bar, and / or iii) The temperature outside the container is set to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, more preferably about 121°C, and / or iv) The container is filled with the solution to a filling volume in accordance with ISO 4802-2:2016(E); Section 7.2, and / or v) The container is filled with the solution until it reaches a volume of [volume / volume] 10% to 100%, preferably 30% to 95%, more preferably about 90%, relative to the volume up to the rim of the container, and / or vi) The solution comprises, preferably ultrapure water, and an acid, preferably one acid, more preferably HX (wherein X is selected from F, Cl, Br and / or I), more preferably HCl, and / or vii) The concentration of the acid is 0.0001 mol / l to 1 mol / l, preferably 0.01 mol / l to 0.5 mol / l, more preferably 0.05 mol / l to 0.2 mol / l, more preferably about 0.1 mol / l, and / or viii) The solution comprises an organic solvent, preferably an alcohol, an ester and / or an ether, more preferably an alcohol, more preferably isopropanol, and / or ix) The specific ratio [volume / volume] of water to the organic solvent is 0.1 to 10, preferably 0.3 to 0.7, more preferably 0.4 to 0.6, more preferably about 0.5, and / or x) The container is preferably closed by a sealing agent during the acid treatment.

[0029] If one or more of the above conditions i) to x), preferably conditions i) to vii) and x), more preferably all of conditions i) to x), the coating is subjected to further stress, and the resulting quality evaluation results reflect a more detailed investigation of the coating's properties regarding resistance to solutions with a low pH.

[0030] In one embodiment, the acid treatment includes the step of bringing an acid solution into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, provided that the following conditions are met: i) The contact time between the acid solution and at least a portion of the alkalized surface and / or heat-treated surface is 1 to 10 hours, preferably about 6 hours. ii) The external pressure of the container is set to ambient pressure + approximately 1 bar. iii) The temperature outside the container is set to approximately 121°C. iv) The container is filled with the solution to a filling volume in accordance with ISO 4802-2:2016(E); Section 7.2. v) The container is filled with the solution until it reaches 90% of its volume, [volume / volume] relative to the volume up to the rim of the container. vi) The solution consists of ultrapure water and HCl as an acid. vii) The concentration of the acid is 0.1 mol / l. viii) The solution contains isopropanol, ix) The ratio [volume / volume] of water to organic solvents is 0.5. x) The container is closed with a sealing seal during the acid treatment.

[0031] In one embodiment of the acid treatment, the contact time between the acid solution and at least a portion of the alkali-treated surface is 1 second to 1 week, preferably 1 minute to 1 day, more preferably 1 hour to 10 hours, and more preferably about 6 hours. In one embodiment, the contact time between the acid solution and at least a portion of the alkali-treated surface is 1 second or more, 1 minute or more, 1 hour or more, or about 6 hours. In one embodiment, the contact time between the acid solution and at least a portion of the alkali-treated surface is 1 week or less, 1 day or less, or 10 hours or less.

[0032] In one embodiment of the acid treatment, the external pressure and temperature of the container are set to 0.5 bar to 4 bar and 100°C to 150°C, ambient pressure + approximately 1 bar and 100°C to 150°C, 0.5 bar to 4 bar and 121°C, or ambient pressure + approximately 1 bar and approximately 121°C.

[0033] In one embodiment of the acid treatment, the solution consists of ultrapure water and HCl as the acid. In one embodiment of the acid treatment, the solution consists of ultrapure water and 0.1 mol / l HCl. In one embodiment of the acid treatment, the solution consists of ultrapure water and 0.1 mol / l acid HX, where X is selected from F, Cl, and Br. In one embodiment of the acid treatment, the solution consists of ultrapure water and 0.05 mol / l to 0.2 mol / l acid HX, where X is selected from F, Cl, and Br. In one embodiment of the acid treatment, the solution contains water and 0.05 mol / l to 0.2 mol / l HCl.

[0034] In one embodiment of the acid treatment, the container is filled with the solution until it reaches 90% of its volume, which is [volume / volume] relative to the volume up to the rim of the container.

[0035] In a preferred embodiment, obtaining quality evaluation results by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface is equivalent to obtaining quality evaluation results by quantifying the content of one or more ions and / or compounds in the treated acid solution. Therefore, the leaching of one or more ions and / or compounds can be reliably identified, and this is quick and inexpensive because no further extraction steps are required.

[0036] In a more preferred embodiment, obtaining a quality evaluation result by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface is equivalent to obtaining a quality evaluation result by quantifying the content of one or more ions, preferably alkali metal ions, more preferably [Na] ions, in the treated acid solution. When the container is a glass container and the substrate of the container contains Na, for example Na2O, quantification of Na ions is particularly preferred. Therefore, in a preferred embodiment, the container is a glass container and the substrate of the container contains Na, for example Na2O.

[0037] In a more preferred embodiment, obtaining quality evaluation results involves quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface, • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic antioxidants; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. The goal is to quantify the content of a substance and obtain quality evaluation results.

[0038] If the container is a polymer container and the base material of the container contains one or more monomers and / or preferably an antioxidant, then quantification of one or more monomers and / or preferably an antioxidant is particularly preferred. Accordingly, in a preferred embodiment, the container is a polymer container and the base material of the container contains one or more monomers and / or preferably an antioxidant, preferably one of the above-mentioned monomers and / or preferably an antioxidant.

[0039] In a preferred embodiment, the quantification is carried out using chromatography, preferably gas chromatography (GC), preferably headspace gas chromatography (HS-GC), gas chromatography-mass spectrometry (GC-MS), and / or headspace gas chromatography-mass spectrometry (HS-GC-MS), and / or liquid chromatography (LC), preferably liquid chromatography-mass spectrometry (LC-MS), and / or The quantification is performed using inductively coupled plasma atomic emission spectrometry (ICP-AES), inductively coupled plasma atomic emission spectrometry (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS), graphite furnace atomic absorption spectrometry (GFAAS), and / or flame atomic absorption spectrometry (FAAS), and / or The aforementioned quantification is carried out using a titration method.

[0040] These methods are particularly preferred because they allow for the reliable determination of the ion and / or compound content.

[0041] In one (preferred) embodiment, the method involves the following steps: • A step of evaluating the suitability of a covered container for storing a solution, preferably a pharmaceutical solution, using the quality evaluation results obtained by the method described herein, and / or • A step of evaluating the stability of a coated container, preferably a coated pharmaceutical container coating, using quality evaluation results obtained by the method described herein, and / or • A step of relating and / or linking the quality evaluation results obtained by the method described herein to a covered container, preferably a covered container as described herein, more preferably a covered pharmaceutical container, more preferably a covered pharmaceutical container as described herein. Includes.

[0042] If the method includes one or more of the above steps, the quality evaluation results are used to reduce complaints and, consequently, costs. These steps can be carried out at the factory where the containers are manufactured and / or tested, and / or at any other location, for example, at the factory where the coated containers are filled, or where the coated containers are sold and / or advertised.

[0043] In one (preferred) embodiment, the method involves the following steps: The step of manufacturing the first coated container and the second coated container using the same manufacturing method, • The method described in any one of the above claims, preferably the method described herein. i The steps include quantifying the leaching from the first container and obtaining a quality evaluation result for the first covered container, and • A step of applying and / or using the quality evaluation results of the first coated container to determine the suitability of the second coated container for storing the solution in the second container, and / or using the quality evaluation results for quality control of the first coated container and / or the second coated container, and / or · A step of applying and / or using the quality evaluation results of the first coated container to determine the suitability of the second coated container for storing the solution in the second container, wherein the first coated container exhibits less than 90%, preferably less than 50%, more preferably less than 30% leaching of one or more ions and / or compounds, more preferably [Na] ions, relative to the hydrolysis resistance limit for the type 1 glass container, and / or · A step of determining the suitability of the second coated container for storing the solution, preferably by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits leaching of one or more ions and / or compounds, more preferably [Na] ions, of less than 90%, preferably less than 50%, more preferably less than 30% of the maximum limit in the hydrolysis resistance test of the container surface in accordance with ISO 4802-2:2016(E), Section 9.2, Classes HCF1 and HCF2, and / or - A step of determining the suitability of the second coated container for storing the solution, preferably by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits leaching of one or more ions and / or compounds at a concentration of 10.00 mg / l or less, preferably 5.00 mg / l or less, more preferably 4.5 mg / l or less, more preferably 4.1 mg / l or less, more preferably 3.2 mg / l or less, more preferably 2.5 mg / l or less, more preferably 2.0 mg / l or less, more preferably 1.5 mg / l or less, more preferably 1.2 mg / l or less, more preferably 1.0 mg / l or less, more preferably 0.75 mg / l or less, more preferably 0.50 mg / l or less, more preferably 0.40 mg / l or less, more preferably 0.30 mg / l or less, more preferably 0.2 mg / l or less, more preferably 0.1 mg / l or less. Preferably include them in this order.

[0044] If the method includes one or more of the above steps, the quality evaluation results are used to reduce complaints and, consequently, costs. These steps can be carried out at the factory where the containers are manufactured and / or tested, and / or at any other location, for example, at the factory where the coated containers are filled, or where the coated containers are sold and / or advertised.

[0045] In one embodiment, the first coated container and the second coated container are manufactured using the same manufacturing method. • Prepare a first container and a second container, where preferably the first and second containers are glass containers, and each of the first and second containers includes a surface. On at least a portion of the first container and the second container, preferably on the inner surface, the following steps are performed: a) A step of surrounding at least a portion of the surfaces of the first container and the second container, preferably the inner surface, with the precursor P1, and b) The step of generating plasma by irradiating the precursor P1. Perform a coating process that includes The coating parameters are selected from the following list: process temperature PT1, pulse duration PD1, microwave generator irradiation frequency, microwave generator input power IP1, precursor P1, pulse irradiation, pulse pause time PP1 between two pulses, total irradiation time TT1, ratio of total pulse duration PD1 [μs] to total pulse pause time PP1 [ms] [μs / ms], process pressure PR1, decrease in process temperature during the coating process, and flow rate of precursor P1.

[0046] In one embodiment, the method comprises the following steps: • The step of preparing the first covered container and the second covered container, The step of quantifying the leaching of the first coated container by the leaching method and obtaining the quality evaluation result of the first coated container, • A step in which the suitability of the second coated container for storing the solution is determined by applying the quality evaluation results of the first coated container, or the second container is quality-controlled using the quality evaluation results. These are preferably included in this order.

[0047] In one embodiment, the method comprises the following steps: • The step of preparing the first covered container and the second covered container, The step of quantifying the leaching of the first coated container by the leaching method and obtaining the quality evaluation result of the first coated container, • A step in which the suitability of the second coated container for storing the solution is determined by applying the quality evaluation results of the first coated container, or the second container is quality-controlled using the quality evaluation results. Preferably, the leaching method includes the following steps: • The step of preparing a container, preferably a covered container, • If the container has two openings, i.e., a syringe, the smaller opening is covered with a sealing material, such as a tip cap. The step of filling the pharmaceutical container with 0.9 × (volume to the rim) 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck), demineralized water (ultrapure water with a purity of 0.1 μS / cm or less at 25°C, similar to DIN ISO 3696 purity 1 analogue)), • The step of closing the container with a sealing seal, such as aluminum foil or a stopper, • The step of placing the container into an autoclave (for example, Systec, model DX-150 (PM-CA-0001-01)), • The container is treated for 3 hours at 121°C and 1 bar above ambient pressure, for example, 2 bar. • The step of opening the aforementioned sealing seal, • The step of emptying the aforementioned container, The container is filled twice with deionized water and rinsed. • If the container is a glass container: Fill the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)), which is diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C), i.e., the same volume used in the alkali treatment, or • If the container is a polymer container: The step of filling the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) and isopropanol (1:1 / vol.%:vol.%), i.e., the same volume used in the alkali treatment, diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C), • The step of closing the aforementioned container with a sealing seal, • The process of placing the container into an autoclave (for example, a Systec model DX-150 (PM-CA-0001-01)) The container is treated for 6 hours at 121°C and at a pressure 1 bar above ambient pressure. • The step of opening the aforementioned sealing seal, • If the container is a glass container: The step of obtaining a value [mg / l] for the leaching of one or more ions and / or compounds, preferably [Na] ions, by FAAS analysis, for example using Varian SpectrAA 280 FS (PE 3-004), to determine the content (mg / l) of one or more ions and / or compounds, preferably [Na] ions, in the 0.1 mol / l HCl solution. • If the container is a polymer container: The content (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the 0.1 mol / l HCl solution is analyzed using LC-MS, for example, a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants. • The following formula A x B / C [In the formula, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is 0.9 × volume up to the edge, and C is the wet internal surface area (cm²) of the container. 2 ) The value (mg / cm 2 Calculate the value [mg / cm³] for the leaching of one or more ions and / or compounds, preferably Na ions or antioxidants. 2 ], that is, the step of obtaining the value i, Includes.

[0048] In one embodiment, the method comprises the following steps: • The step of preparing the first covered container and the second covered container, The step of quantifying the leaching of the first coated container by the leaching method and obtaining the quality evaluation result of the first coated container, • A step in which the suitability of the second coated container for storing the solution is determined by applying the quality evaluation results of the first coated container, or the second container is quality-controlled using the quality evaluation results. Preferably, the leaching method includes the following steps: • The step of preparing a container, preferably a covered container, • If the container has two openings, i.e., a syringe, the smaller opening is covered with a sealing material, such as a tip cap. The step of filling the pharmaceutical container with 0.9 × (volume to the rim) 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck), demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having 0.1 μS / cm or less at 25°C)), • The step of closing the container with a sealing seal, such as aluminum foil or a stopper, • The step of placing the container into an autoclave (for example, Systec, model DX-150 (PM-CA-0001-01)), • The container is treated for 3 hours at 121°C and 1 bar above ambient pressure, for example, 2 bar. • The step of opening the aforementioned sealing seal, • The step of emptying the aforementioned container, The container is filled twice with deionized water and rinsed. - A step of filling the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)), which is diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a purity of 0.1 μS / cm or less at 25°C), i.e., the same volume used in the alkali treatment. • The step of closing the aforementioned container with a sealing seal, • The process of placing the container into an autoclave (for example, a Systec model DX-150 (PM-CA-0001-01)) The container is treated for 6 hours at 121°C and at a pressure 1 bar above ambient pressure. • The step of opening the aforementioned sealing seal, • The step of emptying the aforementioned container, The container is filled twice with deionized water and rinsed. The container is preferably dried with air. • A step of filling the pharmaceutical container with 0.9 × (volume up to the rim) of n-hexane, that is, the same volume used in the alkali treatment, • The pharmaceutical container is shaken in an orbital shaker (80 rpm) at room temperature for 30 minutes. - The step of analyzing the content (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the hexane solution using LC-MS, for example, a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants. • The following formula A x B / C [In the formula, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is 0.9 × volume up to the edge, and C is the wet internal surface area (cm²) of the container. 2 ) The value (mg / cm 2 Calculate the value [mg / cm³] for the leaching of one or more ions and / or compounds, preferably Na ions or antioxidants. 2 ], that is, the step of obtaining the value i, Includes.

[0049] In one embodiment, the method comprises the following steps: · Preparing a first coated container and a second coated container; · Quantifying the leaching of the first coated container by a leaching method to obtain a quality evaluation result of the first coated container; · Applying the quality evaluation result of the first coated container to identify the suitability of the second coated container for storing a solution or to perform quality control on the second container using the quality evaluation result; preferably including these steps in this order, where the leaching method includes the following steps: · Preparing a container, preferably the same container used for the above method L; i · When the container has two openings, i.e., when it is a syringe, covering the smaller opening with a sealing material, such as a tip cap; · Filling the pharmaceutical container with a solution of 0.9 × (volume to the edge); · Closing the container with a sealing seal; · Placing the container in a beaker, such as a stainless steel or aluminum beaker; · Filling the beaker with a 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck), deionized water (having a conductivity of 0.1 μS / cm or less at 25 °C, similar to the purity of DIN ISO 3696 ultrapure water)) up to the same liquid level as the liquid level inside the container; · Closing the beaker with a sealing material; · Placing the beaker in an autoclave (e.g., Systec, model DX - 150 (PM - CA - 0001 - 01)); · Treating the beaker at 121 °C for 3 hours and 1 bar above ambient pressure, e.g., 2 bar; · Opening the sealing material of the beaker; · Emptying the beaker; · Washing the outside of the container by filling the beaker with deionized water twice and rinsing, and rinsing the outside of the container with deionized water; ​The step of placing the container back into a beaker, for example, a stainless steel or aluminum beaker. • If the container is a glass container: Fill the beaker with a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a liquid level of 0.1 μS / cm or less at 25°C) until the liquid level reaches the same level as the liquid level in the container, that is, fill it with the same volume as used in the alkali treatment, or • If the container is a polymer container: The beaker is filled with a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) and isopropanol (1:1 / vol.%:vol.%) diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C) until the liquid level reaches the same level as the liquid level in the container, i.e., the same volume used in the alkali treatment. • The step of closing the beaker with a sealing material, • The step of placing the beaker into an autoclave (for example, Systec, Model DX-150 (PM-CA-0001-01)), The beaker is treated for 6 hours at 121°C and 1 bar above ambient pressure. • The step of opening the beaker, • If the container is a glass container: The step of obtaining a value [mg / l] for the leaching of one or more ions and / or compounds, preferably [Na] ions, by FAAS analysis, for example using Varian SpectrAA 280 FS (PE 3-004), to determine the content (mg / l) of one or more ions and / or compounds, preferably [Na] ions, in the 0.1 mol / l HCl solution. • If the container is a polymer container: The content (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the 0.1 mol / l HCl solution is analyzed using LC-MS, for example, a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants. • The following formula A x B / C [In the formula, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is the volume of the solution in the beaker, and C is the wet external surface area (cm²) of the container. 2 ) The value (mg / cm 2 Calculate the value for the leaching of one or more ions and / or compounds [mg / cm³]. 2 ], that is, the step of obtaining the value o, Includes.

[0050] In a preferred embodiment, the method comprises the steps of: filling a coated container, preferably a second coated container, with a solution, preferably a pharmaceutical composition, more preferably having a pH of 4 to 14, preferably having a pH greater than 7 to 12, and more preferably having a pH of 9 to 11. In a preferred embodiment, the pharmaceutical composition comprises one or more compounds expressly referred to in International Publication No. 2018 / 157097 (WO2018 / 157097 A1), which is incorporated herein by reference.

[0051] One embodiment of the present invention is the use of quality evaluation results obtained by the method described herein for evaluating the suitability of a coated container, preferably a coated pharmaceutical container, for the storage of a solution, preferably a pharmaceutical solution, and / or for quality control in the manufacture of the coated container. The use of said quality evaluation results reduces complaints and, consequently, costs. The quality evaluation results can be used in the factory where the container is manufactured and / or tested, and / or anywhere else, for example, in the factory where the coated container is filled, or where the coated container is sold and / or advertised.

[0052] Covered container One embodiment of the present invention is a method, preferably the method described herein, in which the extraction of one or more ions and / or compounds is obtained by the method described herein. i A coated container obtained by such means, wherein the leaching of one or more ions and / or compounds is 5.00 mg / l or less.

[0053] In one (preferred) embodiment, a method L, preferably described herein, is obtained by the method described herein. i The leaching of one or more ions and / or compounds obtained by this method is 10.00 mg / l or less, preferably 5.00 mg / l or less, more preferably 4.5 mg / l or less, more preferably 4.1 mg / l or less, more preferably 3.2 mg / l or less, more preferably 2.5 mg / l or less, more preferably 2.0 mg / l or less, more preferably 1.5 mg / l or less, more preferably 1.2 mg / l or less, more preferably 1.0 mg / l or less, more preferably 0.75 mg / l or less, more preferably 0.50 mg / l or less, more preferably 0.40 mg / l or less, more preferably 0.30 mg / l or less, more preferably 0.2 mg / l or less, and more preferably 0.1 mg / l or less. Therefore, tolerance over a wide pH range, especially at high pH values, can be further improved.

[0054] In one (preferred) embodiment, a method L, preferably described herein, is obtained by the method described herein.i The leaching of one or more ions and / or compounds obtained by this method is 100% or less, preferably 90% or less, more preferably 50% or less, more preferably 50% or less, more preferably 1% or more, and 30% or less, of the maximum limit in the hydrolysis resistance test of the container surface in accordance with ISO 4802-2:2016(E), Section 9.2, Classes HCF1 and HCF2. Therefore, resistance over a wide pH range, especially at high pH values, can be further improved.

[0055] In one (preferred) embodiment, a method L, preferably described herein, is obtained by the method described herein. i a is the leaching of one or more ions and / or compounds obtained by this, where a ≤ b × c, If the volume of the container (0.9 × (volume to the rim)) is ≤ 1 ml, then b is 5.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >1 ml and ≤2 ml, then b is 4.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >2 ml and ≤3 ml, then b is 4.10 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >3 ml and ≤5 ml, then b is 3.20 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >5 ml and ≤10 ml, then b is 2.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >10 ml and ≤20 ml, then b is 2.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >20 ml and ≤50 ml, then b is 1.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >50 ml and ≤100 ml, then b is 1.20 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >100 ml and ≤200 ml, then b is 1.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >200 ml and ≤500 ml, then b is 0.75 mg / l, and If the volume of the container (0.9 × (volume to the rim)) is >500 ml, then b is 0.50 mg / l, and c is 1.00, preferably 0.90, more preferably 0.80, more preferably 0.70, more preferably 0.60, more preferably 0.50, more preferably 0.40, more preferably 0.30, more preferably 0.20, more preferably 0.15, more preferably 0.10, more preferably 0.08, and more preferably 0.05. Since leaching depends on the size of the container (see ISO 4802-2:2016(E)), the above parameters are particularly preferable for very small and large containers. When the above parameters are satisfied, tolerance over a wide pH range, especially at high pH values, can be further improved. In a more preferred embodiment, a is 0 mg / l or more, preferably 0.001 mg / l or more, more preferably 0.01 mg / l or more, more preferably 0.1 mg / l or more, and more preferably 0.2 mg / l or more.

[0056] In one (preferred) embodiment, the coated container includes an inner surface and an outer surface, and at least a portion of the inner surface is covered by a coating, The aforementioned coated container is given by the following formula: i / o≦d In this case, the value d([mg / cm 2 ] / [mg / cm 2 ]) indicates, In the above formula, i is obtained by the method described herein, preferably by the method described herein. i The leaching of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and o is the leaching of one or more ions and / or compounds from the substrate of the coated container (mg / cm³). 2 ) and / or the method described herein L oThis is obtained by [method]. When this parameter is satisfied, the protection of the pharmaceutical composition stored inside the container is improved, and is particularly improved compared to the same but uncoated container. Most known coatings for containers are obtained by [method] of the method described herein and method L described herein. i Since it has no resistance whatsoever to alkaline and acidic treatments, which are also part of it, the coating of the coated container will exhibit excellent resistance to solutions with high or low pH when the above parameters are met.

[0057] In one embodiment, the coated container includes an inner surface and an outer surface, and at least a portion of the inner surface is covered by a coating, The aforementioned coated container is given by the following formula: i / o≦d In this case, the value d([mg / cm 2 ] / [mg / cm 2 ]) indicates, In the above formula, i is the method L i The leaching of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and o is the leaching of one or more ions and / or compounds from the substrate of the coated container (mg / cm³). 2 ) and the method L o It is obtained by [method].

[0058] In one embodiment, the coated container includes an inner surface and an outer surface, and at least a portion of the inner surface is covered by a coating, The aforementioned coated container is given by the following formula: i / o≦d In this case, the value d([mg / cm 2 ] / [mg / cm 2 ]) indicates, In the above formula, i is the method L i The leaching of one or more ions and / or compounds (mg / cm³) obtained by this method. 2) and o is the leaching of one or more ions and / or compounds from the substrate of the coated container (mg / cm³). 2 ) and the method L o Obtained by, The aforementioned method L i The one or more ions and / or compounds obtained by this method are the same type of ions and / or compounds as the one or more ions and / or compounds in the substrate of the coated container, and the method L o It is obtained by [method].

[0059] In a more preferred embodiment, d is 0.80, preferably 0.70, more preferably 0.60, more preferably 0.50, more preferably 0.40, more preferably 0.30, more preferably 0.20, more preferably 0.14, more preferably 0.10, and more preferably 0.07. Thus, the protection of the pharmaceutical composition stored inside the container is further improved.

[0060] In one (preferred) embodiment, the covered container is of the following formula i / o≧e In this case, a value of e([mg / cm²] is 0.00, preferably 0.01, more preferably 0.02, more preferably 0.05, more preferably 0.10, more preferably 0.12, and more preferably 0.14. 2 ] / [mg / cm 2 This indicates ]).

[0061] In a more preferred embodiment, i is 1.0 × 10 -10 mg / cm 2 ~1.0×10 -3 mg / cm 2 Preferably 1.0 × 10 -8 mg / cm 2 ~6.5×10 -4 mg / cm 2 , comfortably 1.0 × 10 -7 mg / cm 2 ~6.0×10 -4 mg / cm 2 , comfortably 1.0 × 10-6 mg / cm 2 ~3.0×10 -4 mg / cm 2 , more comfortable 7.0×10 -6 mg / cm 2 ~3.0×10 -5 mg / cm 2 Therefore, the protection of the pharmaceutical composition stored inside the container is further improved.

[0062] In a more preferred embodiment, o is 1.1 × 10 -5 mg / cm 2 ~1.0×10 -1 mg / cm 2 Preferably 1.0 × 10 -4 mg / cm 2 ~1.0×10 -2 mg / cm 2 , more 6.5 × 10 -4 mg / cm 2 ~1.0×10 -3 mg / cm 2 , more preferably 6.8 × 10 -4 mg / cm 2 ~7.5×10 -4 mg / cm 2 Therefore, the lower the value o, the better the resistance of the container's base material. Consequently, the lower the value o, the better the protection of the pharmaceutical composition stored inside the container.

[0063] In a more preferred embodiment, i is the method L described in this application. i Extraction of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and / or o is a method described in this application L o Extraction of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 Therefore, values ​​i and o can be reliably identified, and only one container is required to identify both parameters. The method L oIt can also be used when the external surface is covered with another coating, for example, a silicone coating or a PICVD coating. Preferably, the method L o When used, the external surface is not coated.

[0064] In a more preferred embodiment, o is the leaching of one or more ions and / or compounds (mg / cm³) from an uncoated container. 2 ) and the uncoated container is obtained by the same manufacturing method as the coated container (but without coating), where o is obtained by the method described herein and / or method L described herein. i This is obtained by [method]. Therefore, the values ​​o and i can be reliably determined by only one method.

[0065] In a more preferred embodiment, the one or more ions and / or compounds are alkali metal ions and / or alkaline earth metal ions, preferably Na ions and / or K ions, more preferably Na ions. When the container is a glass container and the substrate of the container contains Na, for example Na2O, quantification of Na ions is particularly preferred. Therefore, in a preferred embodiment, the container is a glass container and the substrate of the container contains Na, for example Na2O.

[0066] In a more preferred embodiment, the one or more ions and / or compounds are • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic antioxidants; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. That is the case.

[0067] In a preferred embodiment, the container is a polymer container, and the base material of the container contains one or more antioxidants and / or, preferably, a monomer.

[0068] The coating process for obtaining a coated container is not particularly limited. In a more preferred embodiment, the coating is obtained by a coating process, preferably by CVD, more preferably by plasma-enhanced chemical vapor deposition (PECVD), plasma-impulse chemical vapor deposition (PICVD), or plasma-assisted chemical vapor deposition (PACVD), preferably by plasma-impulse chemical vapor deposition (PICVD). This method is particularly suitable for providing a coating with excellent resistance over a wide pH range, improved resistance at high pH values, high chemical stability, and excellent adhesion properties.

[0069] In a more preferred embodiment, the coating is obtained by a pretreatment and coating process, preferably by a CVD method, more preferably by a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma-impulse chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably by a plasma-impulse chemical vapor deposition (PICVD) method, where the pretreatment is performed before the coating process. This method is particularly suitable for applying coatings, further improving resistance over a wide pH range and at high pH values, and further improving chemical stability and adhesion properties.

[0070] In a more preferred embodiment, the coating process consists of the following steps: • The step of preparing a container including a surface, preferably a glass container, • A step in which a coating process is carried out on at least a portion of the container, preferably on the inner surface, a) A step of surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P1, and b) A step of generating plasma by irradiating the precursor P1, The above steps include the following, wherein at least one, preferably all, of the following parameters are satisfied: i) The process temperature PT1 is 200°C to the Tg of the glass component, preferably 200°C to 500°C, more preferably 220°C to 450°C, more preferably 240°C to 320°C, more preferably 250°C to 300°C, and / or ii) The pulse duration PD1 of the plasma is 50 μs or less, preferably 40 μs or less, preferably 30 μs or less, more preferably 20 μs or less, more preferably 15 μs or less, more preferably 12 μs or less, more preferably 8 μs or less, more preferably 6 μs or less, more preferably 4 μs or less, more preferably about 3 μs, and / or iii) The pulse duration PD1 of the plasma is 0.1 μs or more, preferably 0.5 μs or more, more preferably 1 μs or more, more preferably 6 μs or more, and / or iv) The irradiation is performed by a microwave generator, preferably with a frequency of 300 MHz to 300 GHz, more preferably 600 MHz to 100 GHz, more preferably 800 MHz to 10 GHz, more preferably 900 MHz to 3 GHz, more preferably about 2.45 GHz, and / or v) The input power IP1, preferably the input power IP1 of the microwave generator, is 1000W to 10000W, preferably 2100W to 8000W, more preferably 2500W to 6700W, more preferably 3000W to 6000W, more preferably 3200W to 5500W, more preferably 4000W to 5000W, and / or vi) Precursor P1 comprises one or more of the following and / or combinations: hexamethyldisiloxane (HMDSO), hexamethyldisilazane (HMDS), tetramethylsilane (TMS), trimethylborazole (TMB), tri(dimethylaminosilyl)-amino-di(dimethylamino)borane (TDADB), tris(trimethylsilyl)borate (TMSB), hexamethylcyclotrisiloxane (HMCTSO), octamethylcyclotetrasiloxane (OMCTS), decamethylcyclopentasiloxane (DMCPS), dodecamethylcyclohexasiloxane (DMCHS), diacetoxy-di-t-butoxysilane (DADBS), tetraethoxysilane (TEOS), tris(trimethylsilyloxy)vinylsilane (TTMSVS), vinyltriethoxysilane (VTES), preferably the precursor P1 is HMDSO, and / or vii) The precursor P1 preferably comprises the elements Si, C, O and H, and / or consists of the elements. viii) The pulse pause time PP1 between two pulses is 1 μs or more, preferably 10 μs or more, more preferably 1 μs to 5 s, more preferably 0.1 ms to 10 ms, more preferably 0.2 ms to 2.0 ms, more preferably 0.3 ms to 1.2 ms, more preferably 0.4 ms to 0.8 ms, and / or ix) The total irradiation time TT1 is 0.1 seconds or more, preferably 1 second or more, more preferably 1 second to 5 minutes, more preferably 3 seconds to 90 seconds, more preferably 5 seconds to 40 seconds, and / or x) The ratio [μs / ms] of the total pulse duration PD1 [μs] to the total pulse pause time PP1 [ms] is 1 or more, preferably 2 or more, more preferably 2 to 50, more preferably 3 to 8, and / or xi) The process pressure PR1 is 0.01 mbar to 500 mbar, preferably 0.1 mbar to 10 mbar, more preferably 0.3 mbar to 5 mbar, more preferably 0.6 mbar to 2.0 mbar, more preferably about 0.8 mbar, and / or xii) During the coating process, the process temperature is increased, preferably steadily, and / or xiii) The process temperature PT1 is at least partially, preferably 220°C or higher, more preferably 240°C or higher, more preferably 250°C or higher, more preferably 255°C or higher, more preferably 270°C or higher, more preferably 280°C or higher, and / or xiv) The flow rate of the precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and more preferably 10 to 15 sccm.

[0071] Preferably, all of the above parameters are satisfied. This method is particularly suitable for applying coatings, further improving resistance over a wide pH range and at high pH values, and further improving chemical stability and adhesion properties.

[0072] In one embodiment, the coating process is carried out using the apparatus described in International Publication No. 03015122 (WO03015122 A1).

[0073] In one embodiment, surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P1 can be understood as exposing at least a portion of the surface of the container, preferably the inner surface, to the precursor P1.

[0074] In one embodiment, surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P1 can be understood as providing at least a portion of the surface of the container, preferably the inner surface, to the precursor P1.

[0075] In one embodiment of the above method, the flow rate of the precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and more preferably 10 to 15 sccm. It is even more preferable that the precursor P1 is chemically pure to at least 99% by mass.

[0076] In a more preferred embodiment, the pretreatment steps are as follows: • The step of preparing a container including a surface, preferably a glass container, • A step in which a coating process is carried out on at least a portion of the container, preferably on the inner surface, a) A step of surrounding at least a portion of the surface of the container, preferably the inner surface, with precursor P2, and b) A step of generating plasma by irradiating the precursor P2, Plasma pretreatment comprising the steps described above, wherein at least one, preferably all, of the following parameters are satisfied: i) The process temperature PT2 is room temperature to the glass Tg of the glass component, preferably room temperature to 450°C, more preferably room temperature to 400°C, more preferably room temperature to 320°C, more preferably room temperature to about 280°C, and / or ii) The pulse duration PD2 of the plasma is 50 ms or less, preferably 40 ms or less, preferably 30 ms or less, more preferably 20 ms or less, more preferably 15 ms or less, more preferably 8 ms or less, more preferably 6 ms or less, more preferably 1 ms or less, more preferably about 0.5 ms, and / or iii) The pulse duration PD2 of the plasma is 0.1 ms or more, preferably 0.2 ms or more, more preferably 0.3 ms or more, more preferably 0.5 ms or more, and / or iv) The irradiation is performed by a microwave generator, preferably with a frequency of 300 MHz to 300 GHz, more preferably 600 MHz to 100 GHz, more preferably 800 MHz to 10 GHz, more preferably 900 MHz to 3 GHz, more preferably about 2.45 GHz, and / or v) The input power IP2, preferably the input power IP2 of the microwave generator, is 1000W to 10000W, preferably 2500W to 8000W, more preferably 4000W to 8000W, more preferably 5000W to 7000W, more preferably 5000W to 6500W, more preferably 5250W to 5750W, and / or vi) The precursor P2 comprises argon, oxygen and / or nitrogen, preferably oxygen, and more preferably the precursor P2 is air, and / or vii) The precursor P2 comprises the element N, for example N2, and / or O, for example O2, preferably N2 and O2, more preferably O2, and / or viii) The pulse pause time PP2 between two pulses is 1 μs or more, preferably 10 μs or more, more preferably 1 μs to 5 s, more preferably 0.1 ms to 10 ms, more preferably 0.5 ms to 2.0 ms, more preferably 1.5 ms to 2.0 ms, more preferably about 1.8 ms, and / or ix) The total irradiation time TT2 is 0.1 seconds or more, preferably 1 second or more, more preferably 1 second to 5 minutes, more preferably 5 seconds to 15 seconds, and / or x) The ratio [ms / ms] of the total pulse duration PD2 [ms] to the total pulse pause time PP2 [ms] is 0.05 or greater, preferably 0.1 or greater, more preferably 0.15 to 5, more preferably 0.2 to 0.5, and / or xi) The process pressure PR2 is 0.01 mbar to 500 mbar, preferably 0.1 mbar to 100 mbar, more preferably 0.5 mbar to 10 mbar, more preferably 0.8 mbar to 6.0 mbar, more preferably 1.0 mbar to 4.0 mbar, and / or xii) During plasma processing, increase the process temperature PT2, preferably steadily, and / or xiii) The process temperature PT2 is at least partially, preferably 220°C or higher, preferably 240°C or higher, more preferably 250°C or higher, more preferably 255°C or higher, more preferably 270°C or higher, more preferably about 280°C or higher, and / or xiv) The flow rate of the precursor P2 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 50 sccm, and more preferably 20 to 30 sccm.

[0077] This method is particularly suitable for surface pretreatment, further improving resistance over a wide pH range and at high pH values, as well as further improving chemical stability and adhesion properties.

[0078] In one embodiment, surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P2 can be understood as exposing at least a portion of the surface of the container, preferably the inner surface, to the precursor P2.

[0079] In one embodiment, surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P2 can be understood as providing at least a portion of the surface of the container, preferably the inner surface, to the precursor P2.

[0080] In a more preferred embodiment, the inner surface of the container, preferably the entire inner surface of the container, is coated. Thus, the pharmaceutical composition is further protected. In a more preferred embodiment, the outer surface of the container is not coated. In a more preferred embodiment, the inner surface of the container, preferably the entire inner surface of the container, is coated, and the outer surface of the container is not coated. Thus, foreign matter of the pharmaceutical composition is further protected. If the outer surface is not coated, the leaching of one or more ions and / or compounds may be similar, preferably identical, to the leaching of the substrate of the container. More preferably, the coating is obtained as described in European Patent Application Publication No. 21164784 (EP21164784), which is incorporated herein by reference.

[0081] In a more preferred embodiment, the base material of the coated container comprises, preferably, glass, borosilicate glass or aluminoborosilicate glass, more preferably borosilicate glass. In a more preferred embodiment, the composition of the glass is, by mass % SiO2: 30-98%, preferably 50-90%, more preferably 70.0-74.0%, B2O3: 0-30%, preferably 3-20%, more preferably 7.0-16.0% Al2O3: 0-30%, preferably 1-15%, more preferably 3.0-6.5% X2O: 0-30%, preferably 1-15%, more preferably 2.0-7.2% (wherein X is selected from Na, K, and Li, preferably X is Na and / or K, more preferably Na), YO: 0-30%, preferably 0.1-5%, more preferably 0.5-1.0% (wherein Y is selected from Ca, Mg, and Ba, preferably Y is Ca and / or Mg), and Preferably unavoidable impurities It contains, preferably consists of, and more preferably the total amount of all unavoidable impurities is 5% by mass or less, preferably 2.5% by mass or less, more preferably 1.0% by mass or less, more preferably 0.5% by mass or less, more preferably 0.1% by mass or less, and / or preferably the impurities are selected from Fe, Ti, Zn, Cu, Mn and Co.

[0082] In a more preferred embodiment, the substrate of the coated container comprises, preferably, a polymer, preferably a cyclic olefin copolymer COC and / or a cyclic olefin polymer COP, more preferably a cyclic olefin copolymer COC. Preferably, the polymer contains an antioxidant.

[0083] In a more preferred embodiment, the base material of the coated container is • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic antioxidants; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. Includes.

[0084] In a further preferred embodiment, the volume to the rim of the container is 0.1 ml to 1000 ml, preferably 0.5 ml to 500 ml, more preferably 1 ml to 250 ml, more preferably 2 ml to 30 ml, more preferably 3 ml to 15 ml, more preferably about 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 11 ml, 12 ml, 13 ml, 14 ml or 15 ml, more preferably 5 to 15 ml. In a further preferred embodiment, the coated container is a coated pharmaceutical container, more preferably a coated vial, a coated syringe, a coated ampoule or a coated cartridge, more preferably a coated vial. In a further preferred embodiment, the coated container is a coated pharmaceutical container, preferably a cartridge or syringe, preferably a syringe, where the smaller opening of the cartridge or syringe, preferably a syringe, is preferably closed with a tip cap and / or stopper. In a more preferred embodiment, at least a portion of the coated surface, at least a portion of the alkali-treated surface, and at least a portion of the acid-treated surface are identical, and / or at least a portion of the coated surface includes at least a portion of the internal surface, preferably at least a portion of the coated surface is a surface that comes into contact with the solution when the coated container is placed upright on a flat surface and filled with a solution having a volume of 10% or more, preferably 30% or more, more preferably 90% or more, of the volume up to the rim of the coated container [volume / volume], and / or at least a portion of the coated surface is a surface that comes into contact with the solution when the coated container is filled to a filling volume in accordance with ISO 4802-2:2016(E), Section 7.2. If one or more of the above parameters are met, the safety of the pharmaceutical composition while stored in the coated container can be further improved.

[0085] In a preferred embodiment, the substrate of the container contains one or more ions and / or compounds. Therefore, the reliable identification of the values ​​described herein can be improved.

[0086] One embodiment of the present invention is i) Covered containers, preferably covered containers as described herein, and ii) A data sheet or storage medium containing quality evaluation results obtained by the method described herein. This is a kit that includes [the following items].

[0087] definition In this application, contact time refers to the time during which a composition, such as an acid composition, is in contact with at least a portion of the surface. The time not included in the contact time is the time required to prepare the sample or to prepare the sample for the next step. The contact time may be the time during which the sample is present in an autoclave that is operating and set to a specific pressure and temperature.

[0088] In this application, a heat-treated surface is a heat-treated coated surface. In this application, the substrate is the material of an uncoated container, such as glass or polymer. In this application, the ambient pressure and temperature are the pressure measured at the time the method is carried out, for example, 1 bar and 20°C.

[0089] In this application, the acid composition is preferably a composition comprising an acid, such as HCl, and a solvent, such as water and / or an organic solvent.

[0090] Unless otherwise specified, ratios in this application always refer to volume ratios, i.e., [volume / volume].

[0091] In this application, monomers are monomers used to produce a substrate for a coated container, preferably made of a polymer, which includes a polymer. Since industrial production methods for polymers are well known, those skilled in the art can easily deduce the corresponding monomers from the polymer. Well-known monomers include, for example, substituted or unsubstituted, preferably unsubstituted norbornene, norbornane, and / or bicyclopentane.

[0092] In this application, unavoidable impurities are impurities that may be contained in the starting material, such as Fe, Ti, Zn, Cu, Mn, and Co. Preferably, the total amount of all unavoidable impurities in the substrate of the coated container is 5% by mass or less, preferably 2.5% by mass or less, more preferably 1.0% by mass or less, more preferably 0.5% by mass or less, more preferably 0.1% by mass or less, and more preferably 0.01% by mass or less.

[0093] In this application, the total irradiation time is the sum of all pulse durations and pulse pauses.

[0094] The temperature during the pretreatment and coating processes in this application refers to the temperature measured at the center of the glass component using a pyrometer. If the container is a container having a cylindrical portion, the temperature during the coating process is measured at the center of the cylindrical portion of the container, for example, a vial.

[0095] Unless otherwise specified, the input power is the forward voltage measured between the irradiation generator, e.g., a microwave generator, and the glass component, measured by, for example, an MW diode (ACTP-1502; damping 10 dB).

[0096] In this application, Tg (glass transition temperature) is measured by differential scanning calorimetry (DSC).

[0097] In this application, ultrapure water refers to water with a purity of 1 similar to DIN ISO 3696, having a purity of ≤0.1 μS / cm at 25°C.

[0098] Even if the quality evaluation method described herein relates to a coated container, a person skilled in the art will recognize that the method can also be applied to an uncoated container, for example, to obtain a reference value. Unless otherwise specified, the volume to the rim in this application refers to the volume to the rim of the container, preferably a coated container.

[0099] Parameters and methods The value of i can be obtained as described in this application. Preferably, i can be obtained by the following method L i It is identified by [the specified method].

[0100] Method L i : In this application, a particularly preferred embodiment of the present invention is as follows: • The step of preparing a container, preferably a covered container, • If the container has two openings, i.e., a syringe, the smaller opening is covered with a sealing material, such as a tip cap. • The step of filling the pharmaceutical container with 0.9 × (volume to the rim) 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck), demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a viscosity of 0.1 μS / cm or less at 25°C), • The step of closing the container with a sealing seal, such as aluminum foil or a stopper, • The step of placing the container into an autoclave (for example, Systec, model DX-150 (PM-CA-0001-01)), • The container is treated for 3 hours at 121°C and 1 bar above ambient pressure, for example, 2 bar. • The step of opening the aforementioned sealing seal, • The step of emptying the aforementioned container, The container is filled twice with deionized water and rinsed. • If the container is a glass container: Fill the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)), which is diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C), i.e., the same volume used in the alkali treatment, or • If the container is a polymer container: The step of filling the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) and isopropanol (1:1 / vol.%:vol.%), i.e., the same volume used in the alkali treatment, diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C), • The step of closing the aforementioned container with a sealing seal, • The process of placing the container into an autoclave (for example, a Systec model DX-150 (PM-CA-0001-01)) The container is treated for 6 hours at 121°C and at a pressure 1 bar above ambient pressure. • The step of opening the aforementioned sealing seal, • If the container is a glass container: The step of obtaining a value [mg / l] for the leaching of one or more ions and / or compounds, preferably [Na] ions, by FAAS analysis, for example using Varian SpectrAA 280 FS (PE 3-004), to determine the content (mg / l) of one or more ions and / or compounds, preferably [Na] ions, in the 0.1 mol / l HCl solution. • If the container is a polymer container: The content (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the 0.1 mol / l HCl solution is analyzed using LC-MS, for example, a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants. • The following formula A x B / C [In the formula, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is 0.9 × volume up to the edge, and C is the wet internal surface area (cm²) of the container.2 ) The value (mg / cm 2 Calculate the value [mg / cm³] for the leaching of one or more ions and / or compounds, preferably Na ions or antioxidants. 2 ], that is, the step of obtaining the value i, Methods including (Method L) i )

[0101] An alternative embodiment is as follows: • The step of preparing a container, preferably a covered container, • If the container has two openings, i.e., a syringe, the smaller opening is covered with a sealing material, such as a tip cap. • The step of filling the pharmaceutical container with 0.9 × (volume to the rim) 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck), demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a viscosity of 0.1 μS / cm or less at 25°C), • The step of closing the container with a sealing seal, such as aluminum foil or a stopper, • The step of placing the container into an autoclave (for example, Systec, model DX-150 (PM-CA-0001-01)), • The container is treated for 3 hours at 121°C and 1 bar above ambient pressure, for example, 2 bar. • The step of opening the aforementioned sealing seal, • The step of emptying the aforementioned container, The container is filled twice with deionized water and rinsed. - A step of filling the pharmaceutical container with 0.9 × (volume to the rim) of a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)), which is diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a purity of 0.1 μS / cm or less at 25°C), i.e., the same volume used in the alkali treatment. • The step of closing the aforementioned container with a sealing seal, · The step of placing the container in an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01)), · The step of treating the container at 121 °C for 6 hours and 1 bar above ambient pressure, · The step of opening the sealing seal, · The step of emptying the container, · The step of filling the container twice with deionized water and rinsing, · The step of drying the container, preferably with air, · The step of filling the pharmaceutical container with 0.9 × (volume to the edge) of n-hexane, i.e., the same volume as used in the alkali treatment, · The step of shaking the pharmaceutical container on an orbital shaker (80 rpm) for 30 minutes at room temperature, · Analyzing the content rate (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the hexane solution using an LC-MS, e.g., a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, · The following formula A × B / C [wherein, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is 0.9 × volume to the edge, and C is the wet internal surface area (cm 2 ) of the container] to calculate a value (mg / cm 2 ) and obtain a value [mg / cm 2 , i.e., value i, for the leaching of one or more ions and / or compounds, preferably Na ions or antioxidants, A method (Method L i ) including the above is included.

[0102] The value o can be obtained by several methods, preferably the value o is specified as described within the present application. The value o is the content rate (mg / cm 2 ) of one or more ions and / or compounds of the base material of the coated container, and / or, preferably or, by the method L o described within the present application, more preferably the value o is obtained by the method L o described within the present application.

[0103] If an uncoated container, which is the same but not coated, used to obtain the value i is available, use that uncoated container to obtain the value o by the above method L i and obtain the content rate (mg / cm 2 ) of one or more ions and / or compounds of the base material of the coated container. If the values i and o are to be obtained by only one container, the value i is obtained by the above method L i and the value o is obtained by the following method L o described below. Preferably, o is obtained by the method L o described below. The method L o can be used for a container coated on the outside or an uncoated container, but preferably the container is not coated on the outside. Preferably, in the methods L i and L o , the largest opening is upward.

[0104] Method L o : [[ID=三十三]]In the present application, the method L o comprises the following steps: · Preparing a container, preferably the same container as used for the above method L i ; · When the container has two openings, i.e., when it shows a syringe, covering the smaller opening with a sealing material, for example, a tip cap; · Filling the pharmaceutical container with a solution of 0.9×(volume to the edge); · Closing the container with a sealing seal; • The step of placing the container into a beaker, for example, a stainless steel or aluminum beaker, - A step in which the beaker is filled with a 0.005 mol / l KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%, Suprapur® (Merck)), demineralized water (ultrapure water with a purity of 1 similar to DIN ISO 3696, having a liquid level of 0.1 μS / cm or less at 25°C) until the liquid level reaches the same level as the liquid level in the container. • The step of closing the beaker with a sealing material, • The step of placing the beaker into an autoclave (for example, Systec, Model DX-150 (PM-CA-0001-01)), • The beaker is treated for 3 hours at 121°C and 1 bar above ambient pressure, for example, 2 bar. • The step of opening the sealant of the beaker, • The step of emptying the beaker, - The beaker is filled twice with deionized water and rinsed, and the outside of the container is washed by rinsing the outer surface with deionized water. The step of placing the container back into a beaker, for example, a stainless steel or aluminum beaker. • If the container is a glass container: Fill the beaker with a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a liquid level of 0.1 μS / cm or less at 25°C) until the liquid level reaches the same level as the liquid level in the container, that is, fill it with the same volume as used in the alkali treatment, or • If the container is a polymer container: The beaker is filled with a 0.1 mol / l HCl solution (30% hydrochloric acid Suprapur® (Merck)) and isopropanol (1:1 / vol.%:vol.%) diluted with demineralized water (ultrapure water similar to purity 1 of DIN ISO 3696, having a concentration of 0.1 μS / cm or less at 25°C) until the liquid level reaches the same level as the liquid level in the container, i.e., the same volume used in the alkali treatment. • The step of closing the beaker with a sealing material, • The step of placing the beaker into an autoclave (for example, Systec, Model DX-150 (PM-CA-0001-01)), The beaker is treated for 6 hours at 121°C and 1 bar above ambient pressure. • The step of opening the beaker, • If the container is a glass container: The step of obtaining a value [mg / l] for the leaching of one or more ions and / or compounds, preferably [Na] ions, by FAAS analysis, for example using Varian SpectrAA 280 FS (PE 3-004), to determine the content (mg / l) of one or more ions and / or compounds, preferably [Na] ions, in the 0.1 mol / l HCl solution. • If the container is a polymer container: The content (mg / l) of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in the 0.1 mol / l HCl solution is analyzed using LC-MS, for example, a Waters I-Class UPLC system equipped with Waters Xevo qTOF, to obtain a value [mg / l] for the leaching of one or more ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants. • The following formula A x B / C [In the formula, A is the above value [mg / l] for the leaching of one or more ions and / or compounds, B is the volume of the solution in the beaker, and C is the wet external surface area (cm²) of the container. 2 ) The value (mg / cm 2 Calculate the value for the leaching of one or more ions and / or compounds [mg / cm³]. 2 ], that is, the step of obtaining the value o, Includes.

[0105] heat treatment In a preferred embodiment, heat treatment may be performed before alkali treatment. In this case, the pharmaceutical glass container is tempered at 330°C for 60 minutes in a preheated furnace under ambient pressure. Either a heat-treated or unheat-treated pharmaceutical glass container can be used for alkali treatment. Unless otherwise specified, pharmaceutical glass containers are unheat-treated pharmaceutical glass containers.

[0106] LC-MS When polymer containers were used, the content of non-volatile organic compounds (NVOCs) in the solution was determined using LC-MS. A Waters Class I UPLC system with Waters Xevo qTOF (APCI) was used in conjunction with a Waters Ascquity UPLC BEH column (100 × 2.1 mm, 1.7 μm) equipped with a C18 pre-column (USP code L1). The following experimental parameters were used: Injection volume: 2 μl; Oven temperature: 40°C; Eluent A: Water + 5 mmol / L ammonium acetate; Eluent B: Methanol + 5 mmol / L ammonium acetate; Flow rate: 0.3 mL / min; Gradient (A / B): 70 / 30 / 0.5 min (hold), to 20 / 80 within 1.0 min, to 16 / 84 within 10.5 min, to 6 / 94 within 1.0 min, to 0 / 100 / 7.0 min (hold) within 5.0 min, to 70 / 30 / 5.5 min (hold) within 0.5 min; APCI probe temperature: 450°C; Source temperature: 120°C; Cone gas flow rate: 150 L / h; Desolvent gas flow rate: 1000 L / h; Corona voltage: 3.0 kV; Scan m / z: 100-2000 amu (positive and negative); Ion source: APCI atmospheric pressure chemical ionization; Method: MS E High CE: 20.00~45.00 eV; Low CE: 4.00 eV. The detection limit for this LC-MS method is estimated to be 0.05 mg / L.

[0107] FAAS (Furnace Atomic Absorption Spectrometry) When examining glass containers, the inorganic ion content in the solution was determined using FAAS. The detection limit for this FAAS method is estimated to be 0.01 mg / L.

[0108] Item To summarize, the embodiments and preferred embodiments are as follows. The scope of protection is defined by the claims. Combinations of two or more embodiments, such as 3, 4 or 8 embodiments, are more preferred. The definitions and general descriptions within this application are preferably also applicable to the following embodiments and preferred embodiments.

[0109] 1. A method for evaluating the quality of a coated container, comprising the following steps: · Preparing a coated container; · Performing an alkali treatment on at least a part of the coated surface of the coated container to obtain an alkali-treated surface; · Performing an acid treatment on at least a part of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution; and · Quantifying the leaching of one or more ions and / or compounds from at least a part of the acid-treated surface to obtain a quality evaluation result The method preferably including these steps in this order.

[0110] 2. The following steps: · Preparing a coated container; · Performing a heat treatment on at least a part of the coated container to obtain a heat-treated surface; · Performing an alkali treatment on at least a part of the heat-treated surface to obtain an alkali-treated surface; · Performing an acid treatment on at least a part of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution; and · Quantifying the leaching of one or more ions and / or compounds from at least a part of the acid-treated surface to obtain a quality evaluation result The method for evaluating the quality of a coated container, preferably as described in item 1, preferably including these steps in this order.

[0111] 3. The alkali treatment is the following steps: · contacting an alkaline solution having a pH of 7 to 14, preferably 9 to 13, more preferably 9.5 to 12.5, and even more preferably 11.7, with at least a part of the surface of the coated container, preferably the heat-treated surface, and · rinsing at least a part of the surface treated with the alkali with ultrapure water, preferably two or more times, more preferably three times, preferably filling and rinsing The method according to item 1 or 2, preferably including these steps in this order, preferably consisting of these steps.

[0112] 4. The method according to any one of items 1 to 3, wherein one or more of the following conditions are satisfied: i) The contact time between the alkaline solution and at least a part of the coated surface and / or the heat-treated surface is from 1 second to 1 week, preferably from 1 minute to 1 day, more preferably from 1 hour to 5 hours, and even more preferably 3 hours, and / or ii) The pressure outside the container is from 0.1 bar to 10 bar, preferably from 0.5 bar to 4 bar, more preferably set 1 bar higher than the ambient pressure, and / or iii) The temperature outside the container is from 20 °C to 200 °C, preferably from 50 °C to 200 °C, more preferably from 100 °C to 150 °C, and even more preferably 121 °C, and / or iv) The container is filled with the solution up to [volume / volume], 10% to 100%, preferably 30% to 95%, and more preferably 90% of the volume up to the edge of the container, and / or v) The solution contains water, preferably ultrapure water, and a base, preferably one base, more preferably XOH (where X is selected from Na, K, Li), and even more preferably KOH, preferably consisting of them, and / or vi) The concentration of the base is from 0.0001 mol / l to 1 mol / l, preferably from 0.001 mol / l to 0.11 mol / l, more preferably from 0.003 mol / l to 0.020 mol / l, and even more preferably 0.005 mol / l, and / or vii) The container is preferably closed by a sealing agent during the alkali treatment.

[0113] 5. The heat treatment described above is • The step of tempering the container. A method according to any one of items 1 to 4, preferably comprising the steps described above.

[0114] 6. A method according to any one of items 1 through 5, provided that one or more of the following conditions are met: i) The tempering time is 1 minute to 1 day, preferably 30 minutes to 6 hours, more preferably 60 minutes, and / or ii) The temperature outside the container during tempering is set to 25°C to the Tg of the container's substrate, preferably 50°C to 500°C, more preferably 100°C to 400°C, more preferably 300°C to 400°C, more preferably 330°C, and / or iii) The pressure during the tempering process is set to 0.1 bar to 10 bar, preferably the ambient pressure.

[0115] 7. The method according to any one of items 1 to 6, wherein the acid treatment comprises the step of bringing an acid solution having a pH of less than 7, preferably 0 to 6, preferably 0 to 3, more preferably 0 to 2, more preferably 1, into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, preferably comprising the step of the above.

[0116] 8. The method according to any one of items 1 to 7, wherein the acid treatment includes the step of bringing an acid solution into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, and preferably consists of the above steps, wherein one or more of the following conditions are met: i) The contact time between the acid solution and at least a portion of the alkalized surface is 1 second to 1 week, preferably 1 minute to 1 day, more preferably 1 hour to 10 hours, more preferably 6 hours, and / or ii) The external pressure of the container is set to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably 1 bar above the ambient pressure, and / or iii) The temperature outside the container is set to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, more preferably 121°C, and / or iv) The container is filled with the solution to a filling volume in accordance with ISO 4802-2:2016(E); Section 7.2, and / or v) The container is filled with the solution until it reaches a volume of [volume / volume] 10% to 100%, preferably 30% to 95%, more preferably 90%, relative to the volume up to the rim of the container, and / or vi) The solution comprises, preferably ultrapure water, and an acid, preferably one acid, more preferably HX (wherein X is selected from F, Cl, Br and / or I), more preferably HCl, and / or vii) The concentration of the acid is 0.0001 mol / l to 1 mol / l, preferably 0.01 mol / l to 0.5 mol / l, more preferably 0.05 mol / l to 0.2 mol / l, more preferably 0.1 mol / l, and / or viii) The solution comprises an organic solvent, preferably an alcohol, an ester and / or an ether, more preferably an alcohol, more preferably isopropanol, and / or ix) The specific ratio [volume / volume] of water to the organic solvent is 0.1 to 10, preferably 0.3 to 0.7, more preferably 0.4 to 0.6, more preferably 0.5, and / or x) The container is preferably closed by a sealing agent during the acid treatment.

[0117] 9. The method according to any one of items 1 to 8, wherein obtaining a quality evaluation result by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface is equivalent to obtaining a quality evaluation result by quantifying the content of one or more ions and / or compounds in the treated acid solution.

[0118] 10. The method according to any one of items 1 to 9, wherein obtaining a quality evaluation result is obtained by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface, or by quantifying the content of one or more ions, preferably alkali metal ions, more preferably [Na] ions, in the treated acid solution.

[0119] 11. To obtain quality evaluation results by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface, the treated acid solution contains • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. The method according to any one of items 1 to 10, which is to quantify the content rate to obtain a quality evaluation result.

[0120] 12. The quantification is carried out using chromatography, preferably gas chromatography (GC), preferably headspace gas chromatography (HS-GC), gas chromatography-mass spectrometry (GC-MS), and / or headspace gas chromatography-mass spectrometry (HS-GC-MS), and / or liquid chromatography (LC), preferably liquid chromatography-mass spectrometry (LC-MS), and / or The quantification is carried out using inductively coupled plasma atomic emission spectrometry (ICP-AES), inductively coupled plasma optical emission spectrometry (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS), graphite furnace atomic absorption spectrometry (GFAAS), and / or flame atomic absorption spectrometry (FAAS), and / or The quantification is carried out using a titration method. The method according to any one of items 1 to 11.

[0121] 13. The following steps: · Using the quality evaluation result obtained by the method according to any one of items 1 to 12 to evaluate the suitability of the coated container for the storage of a solution, preferably a pharmaceutical solution, and / or · Using the quality evaluation result obtained by the method according to any one of items 1 to​​​​​​​​​ • A method according to any one of items 1 to 13, preferably a method described herein. i The steps include quantifying the leaching from the first container and obtaining a quality evaluation result for the first covered container, and • A step of applying and / or using the quality evaluation results of the first coated container to determine the suitability of the second coated container for storing the solution in the second container, and / or using the quality evaluation results to quality control the first coated container and / or the second coated container, and / or · A step of applying and / or using the quality evaluation results of the first coated container to determine the suitability of the second coated container for storing the solution in the second container, wherein the first coated container exhibits less than 90%, preferably less than 50%, more preferably less than 30% leaching of one or more ions and / or compounds, more preferably [Na] ions, relative to the hydrolysis resistance limit for the type 1 glass container, and / or · A step of determining the suitability of the second coated container for storing the solution, preferably for storage in the second container, by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits leaching of one or more ions and / or compounds, preferably [Na] ions, of less than 90%, preferably less than 50%, more preferably less than 30% of the maximum limit in the hydrolysis resistance test of the container surface in accordance with ISO 4802-2:2016(E), Section 9.2, Classes HCF1 and HCF2, and / or - A step of determining the suitability of the second coated container for storing the solution, preferably by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits leaching of one or more ions and / or compounds at a concentration of 10.00 mg / l or less, preferably 5.00 mg / l or less, more preferably 4.5 mg / l or less, more preferably 4.1 mg / l or less, more preferably 3.2 mg / l or less, more preferably 2.5 mg / l or less, more preferably 2.0 mg / l or less, more preferably 1.5 mg / l or less, more preferably 1.2 mg / l or less, more preferably 1.0 mg / l or less, more preferably 0.75 mg / l or less, more preferably 0.50 mg / l or less, more preferably 0.40 mg / l or less, more preferably 0.30 mg / l or less, more preferably 0.2 mg / l or less, more preferably 0.1 mg / l or less. A method preferably according to any one of items 1 to 13, preferably comprising in this order.

[0123] 15. The following steps: - A step of filling a first coated container with a solution, preferably a pharmaceutical composition, more preferably a pharmaceutical solution having a pH of 4 to 14, preferably a pH greater than 7 to 12, more preferably a pH of 9 to 11. A method according to any one of items 1 through 14, including the method described in item 1 through 14.

[0124] 16. Use of quality assessment results obtained by any one of items 1 to 12 for evaluating the suitability of a covered container, preferably a covered pharmaceutical container, for the storage of a solution, preferably a pharmaceutical solution, and / or for quality control of the manufacture of a covered container.

[0125] 17. Leaving one or more ions and / or compounds is obtained by a method described in any one of items 1 to 16, preferably by method L described herein. iA coated container obtained by and having an elution of one or more ions and / or compounds of 5.00 mg / l or less.

[0126] 18. The extraction of one or more ions and / or compounds is obtained by any one of the methods described in items 1 to 17, preferably by method L described herein. i A method, use, and / or coated container preferably according to any one of items 1 to 17, wherein the leaching of one or more ions and / or compounds is 10.00 mg / l or less, preferably 5.00 mg / l or less, more preferably 4.5 mg / l or less, more preferably 4.1 mg / l or less, more preferably 3.2 mg / l or less, more preferably 2.5 mg / l or less, more preferably 2.0 mg / l or less, more preferably 1.5 mg / l or less, more preferably 1.2 mg / l or less, more preferably 1.0 mg / l or less, more preferably 0.75 mg / l or less, more preferably 0.50 mg / l or less, more preferably 0.40 mg / l or less, more preferably 0.30 mg / l or less, more preferably 0.2 mg / l or less, and more preferably 0.1 mg / l or less.

[0127] 19. Method L obtained by any one of items 1 to 18, preferably as described herein. i A container, used and / or coated by the method described in any one of items 1 to 18, wherein the leaching of one or more ions and / or compounds obtained by means of is 100% or less, preferably 90% or less, more preferably 50% or less, more preferably 50% or less, more preferably 1% or more and 30% or less, relative to the maximum limit in the hydrolysis resistance test of the container surface in accordance with ISO 4802-2:2016(E), Section 9.2, Classes HCF1 and HCF2.

[0128] 20. Method L obtained by any one of items 1 to 19, preferably as described herein. ia is the leaching of one or more ions and / or compounds obtained by this method, where, a ≤ b × c, If the volume of the container (0.9 × (volume to the rim)) is ≤ 1 ml, then b is 5.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >1 ml and ≤2 ml, then b is 4.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >2 ml and ≤3 ml, then b is 4.10 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >3 ml and ≤5 ml, then b is 3.20 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >5 ml and ≤10 ml, then b is 2.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >10 ml and ≤20 ml, then b is 2.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >20 ml and ≤50 ml, then b is 1.50 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >50 ml and ≤100 ml, then b is 1.20 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >100 ml and ≤200 ml, then b is 1.00 mg / l. If the volume of the container (0.9 × (volume to the rim)) is >200 ml and ≤500 ml, then b is 0.75 mg / l, and If the volume of the container (0.9 × (volume to the rim)) is >500 ml, then b is 0.50 mg / l, and c is 1.00, preferably 0.90, more preferably 0.80, more preferably 0.70, more preferably 0.60, more preferably 0.50, more preferably 0.40, more preferably 0.30, more preferably 0.20, more preferably 0.15, more preferably 0.10, more preferably 0.08, more preferably 0.05. Preferably, the method, use, and / or covered container according to any one of items 1 to 19.

[0129] 21. Method L obtained by any one of items 1 to 20, preferably as described herein. i a is the leaching of one or more ions and / or compounds obtained by this, where a is 0 mg / l or more, preferably 0.001 mg / l or more, more preferably 0.01 mg / l or more, more preferably 0.1 mg / l or more, and more preferably 0.2 mg / l or more. Preferably, the method, use, and / or covered container according to any one of items 1 to 20.

[0130] 22. The coated container includes an inner surface and an outer surface, and at least a portion of the inner surface is covered by a coating, The coated container is given by the following formula: i / o≦d In this case, the value d([mg / cm 2 ] / [mg / cm 2 ]) indicates, In the above formula, i is obtained by any one of the methods described in item 1 to 21, preferably by method L described herein. i The leaching of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and o is the leaching of one or more ions and / or compounds from the substrate of the coated container (mg / cm³). 2 ) and / or the method described herein L o Obtained by, Preferably, the method, use, and / or covered container according to any one of items 1 to 21.

[0131] 23. Preferably the method, use and / or coated container according to any one of items 1 to 22, wherein d is 0.80, preferably 0.70, more preferably 0.60, more preferably 0.50, more preferably 0.40, more preferably 0.30, more preferably 0.20, more preferably 0.14, more preferably 0.10, and more preferably 0.07.

[0132] 24. The coated container is defined by the following formula: i / o≧e In this case, a value of e([mg / cm²] is 0.00, preferably 0.01, more preferably 0.02, more preferably 0.05, more preferably 0.10, more preferably 0.12, and more preferably 0.14. 2 ] / [mg / cm 2 ]) indicates, In the above formula, i is obtained by any one of the methods described in item 1 to 23, preferably by method L described herein. i The leaching of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and o is the leaching of one or more ions and / or compounds from the substrate of the coated container (mg / cm³). 2 ) and / or the method described herein L o Obtained by, Preferably, the method, use, and / or covered container according to any one of items 1 to 23.

[0133] 25. i is 1.0 × 10 -10 mg / cm 2 ~1.0×10 -3 mg / cm 2 Preferably 1.0 × 10 -8 mg / cm 2 ~6.5×10 -4 mg / cm 2 , comfortably 1.0 × 10 -7 mg / cm 2 ~6.0×10 -4 mg / cm 2 , comfortably 1.0 × 10-6 mg / cm 2 ~3.0×10 -4 mg / cm 2 , more comfortable 7.0×10 -6 mg / cm 2 ~3.0×10 -5 mg / cm 2 The container is preferably a container covered by, using, or using the method described in any one of items 1 to 24.

[0134] 26. o is 1.1 × 10 -5 mg / cm 2 ~1.0×10 -1 mg / cm 2 Preferably 1.0 × 10 -4 mg / cm 2 ~1.0×10 -2 mg / cm 2 , more 6.5 × 10 -4 mg / cm 2 ~1.0×10 -3 mg / cm 2 , more preferably 6.8 × 10 -4 mg / cm 2 ~7.5×10 -4 mg / cm 2 The container is preferably a container covered by, using, or using the method described in any one of items 1 to 25.

[0135] 27. Method L in which i is described in this application i Extraction of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) and Method L in which o is described in this application o Extraction of one or more ions and / or compounds (mg / cm³) obtained by this method. 2 ) Preferably, the method, use, and / or covered container according to any one of items 1 to 26.

[0136] 28. Leakage of one or more ions and / or compounds from an uncoated container (mg / cm³) 2) and the uncoated container is obtained in the same manner as the coated container, where o is obtained by the method described in any one of items 1 to 27 and / or by method Li described herein, preferably by the method described in any one of items 1 to 27, use and / or coated container.

[0137] 29. The method, use, and / or coated container preferably according to any one of items 1 to 28, wherein the one or more ions and / or compounds are alkali metal ions and / or alkaline earth metal ions, preferably Na ions and / or K ions, more preferably Na ions.

[0138] 30. The one or more ions and / or compounds described above, • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic antioxidants; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. The container is preferably a container covered by, using, or using the method described in any one of items 1 to 29.

[0139] 31. The coating is obtained by a coating process, preferably by a CVD method, more preferably by a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma-impulse chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably by a plasma-impulse chemical vapor deposition (PICVD) method, and is used, used, and / or coated container according to any one of items 1 to 30.

[0140] 32. The coating is obtained by a pretreatment and coating process, preferably by a CVD method, more preferably by a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma-impulse chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably by a plasma-impulse chemical vapor deposition (PICVD) method, wherein the pretreatment is performed before the coating process, preferably by the method, use and / or coated container described in any one of items 1 to 31.

[0141] 33. The coating process consists of the following steps: • The step of preparing a container including a surface, preferably a glass container, • A step in which a coating process is carried out on at least a portion of the container, preferably on the inner surface, a) A step of surrounding at least a portion of the surface of the container, preferably the inner surface, with the precursor P1, and b) A step of generating plasma by irradiating the precursor P1, The steps include the above, wherein at least one, preferably all, of the following parameters are satisfied, preferably the method, use and / or covered container according to any one of items 1 to 32: i) The process temperature PT1 is 200°C to the Tg of the glass component, preferably 200°C to 500°C, more preferably 220°C to 450°C, more preferably 240°C to 320°C, more preferably 250°C to 300°C, and / or ii) The pulse duration PD1 of the plasma is 50 μs or less, preferably 40 μs or less, preferably 30 μs or less, more preferably 20 μs or less, more preferably 15 μs or less, more preferably 12 μs or less, more preferably 8 μs or less, more preferably 6 μs or less, more preferably 4 μs or less, more preferably 3 μs, and / or iii) The pulse duration PD1 of the plasma is 0.1 μs or more, preferably 0.5 μs or more, more preferably 1 μs or more, more preferably 6 μs or more, and / or iv) The irradiation is performed by a microwave generator, preferably with a frequency of 300 MHz to 300 GHz, more preferably 600 MHz to 100 GHz, more preferably 800 MHz to 10 GHz, more preferably 900 MHz to 3 GHz, more preferably 2.45 GHz, and / or v) The input power IP1, preferably the input power IP1 of the microwave generator, is 1000W to 10000W, preferably 2100W to 8000W, more preferably 2500W to 6700W, more preferably 3000W to 6000W, more preferably 3200W to 5500W, more preferably 4000W to 5000W, and / or vi) Precursor P1 comprises one or more of the following and / or combinations: hexamethyldisiloxane (HMDSO), hexamethyldisilazane (HMDS), tetramethylsilane (TMS), trimethylborazole (TMB), tri(dimethylaminosilyl)-amino-di(dimethylamino)borane (TDADB), tris(trimethylsilyl)borate (TMSB), hexamethylcyclotrisiloxane (HMCTSO), octamethylcyclotetrasiloxane (OMCTS), decamethylcyclopentasiloxane (DMCPS), dodecamethylcyclohexasiloxane (DMCHS), diacetoxy-di-t-butoxysilane (DADBS), tetraethoxysilane (TEOS), tris(trimethylsilyloxy)vinylsilane (TTMSVS), vinyltriethoxysilane (VTES), preferably the precursor P1 is HMDSO, and / or vii) The precursor P1 preferably comprises the elements Si, C, O and H, and / or consists of the elements. viii) The pulse pause time PP1 between two pulses is 1 μs or more, preferably 10 μs or more, more preferably 1 μs to 5 s, more preferably 0.1 ms to 10 ms, more preferably 0.2 ms to 2.0 ms, more preferably 0.3 ms to 1.2 ms, more preferably 0.4 ms to 0.8 ms, and / or ix) The total irradiation time TT1 is 0.1 seconds or more, preferably 1 second or more, more preferably 1 second to 5 minutes, more preferably 3 seconds to 90 seconds, more preferably 5 seconds to 40 seconds, and / or x) The ratio [μs / ms] of the total pulse duration PD1 [μs] to the total pulse pause time PP1 [ms] is 1 or more, preferably 2 or more, more preferably 2 to 50, more preferably 3 to 8, and / or xi) The process pressure PR1 is 0.01 mbar to 500 mbar, preferably 0.1 mbar to 10 mbar, more preferably 0.3 mbar to 5 mbar, more preferably 0.6 mbar to 2.0 mbar, more preferably 0.8 mbar, and / or xii) During the coating process, the process temperature is increased, preferably steadily, and / or xiii) The process temperature PT1 is at least partially, preferably at the start of the coating process, 220°C or higher, preferably 240°C or higher, more preferably 250°C or higher, more preferably 255°C or higher, more preferably 270°C or higher, more preferably 280°C or higher, and / or xiv) The flow rate of the precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and more preferably 10 to 15 sccm.

[0142] 34. The aforementioned pretreatment consists of the following steps: • The step of preparing a container including a surface, preferably a glass container, • A step in which a coating process is carried out on at least a portion of the container, preferably on the inner surface, a) A step of surrounding at least a portion of the surface of the container, preferably the inner surface, with precursor P2, and b) A step of generating plasma by irradiating the precursor P2, Plasma pretreatment comprising the steps described above, wherein at least one, preferably all, of the following parameters are satisfied, preferably the method, use and / or covered container according to any one of items 1 to 33: i) The process temperature PT2 is room temperature to the glass Tg of the glass component, preferably room temperature to 450°C, more preferably room temperature to 400°C, more preferably room temperature to 320°C, more preferably room temperature to 280°C, and / or ii) The pulse duration PD2 of the plasma is 50 ms or less, preferably 40 ms or less, preferably 30 ms or less, more preferably 20 ms or less, more preferably 15 ms or less, more preferably 8 ms or less, more preferably 6 ms or less, more preferably 1 ms or less, more preferably 0.5 ms, and / or iii) The pulse duration PD2 of the plasma is 0.1 ms or more, preferably 0.2 ms or more, more preferably 0.3 ms or more, more preferably 0.5 ms or more, and / or iv) The irradiation is performed by a microwave generator, preferably with a frequency of 300 MHz to 300 GHz, more preferably 600 MHz to 100 GHz, more preferably 800 MHz to 10 GHz, more preferably 900 MHz to 3 GHz, more preferably 2.45 GHz, and / or v) The input power IP2, preferably the input power IP2 of the microwave generator, is 1000W to 10000W, preferably 2500W to 8000W, more preferably 4000W to 8000W, more preferably 5000W to 7000W, more preferably 5000W to 6500W, more preferably 5250W to 5750W, and / or vi) The precursor P2 comprises oxygen and / or nitrogen, preferably oxygen, and more preferably the precursor P2 is air, and / or vii) The precursor P2 comprises the element N, for example N2, and / or O, for example O2, preferably N2 and O2, more preferably O2, and / or viii) The pulse pause time PP2 between two pulses is 1 μs or more, preferably 10 μs or more, more preferably 1 μs to 5 s, more preferably 0.1 ms to 10 ms, more preferably 0.5 ms to 2.0 ms, more preferably 1.5 ms to 2.0 ms, more preferably 1.8 ms, and / or ix) The total irradiation time TT2 is 0.1 seconds or more, preferably 1 second or more, more preferably 1 second to 5 minutes, more preferably 5 seconds to 15 seconds, and / or x) The ratio [ms / ms] of the total pulse duration PD2 [ms] to the total pulse pause time PP2 [ms] is 0.05 or greater, preferably 0.1 or greater, more preferably 0.15 to 5, more preferably 0.2 to 0.5, and / or xi) The process pressure PR2 is 0.01 mbar to 500 mbar, preferably 0.1 mbar to 100 mbar, more preferably 0.5 mbar to 10 mbar, more preferably 0.8 mbar to 6.0 mbar, more preferably 1.0 mbar to 4.0 mbar, and / or xii) During plasma processing, increase the process temperature PT2, preferably steadily, and / or xiii) The process temperature PT2 is at least partially, preferably 220°C or higher, preferably 240°C or higher, more preferably 250°C or higher, more preferably 255°C or higher, more preferably 270°C or higher, more preferably 280°C or higher, and / or xiv) The flow rate of the precursor P2 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 50 sccm, and more preferably 20 to 30 sccm.

[0143] 35. A container having an inner surface, preferably the entire inner surface, covered, preferably by the method, use, and / or covered container according to any one of items 1 to 34.

[0144] 36. A container whose outer surface is not coated, preferably according to any one of items 1 to 35, used and / or coated.

[0145] 37. A coated container preferably made of the method, use and / or coated container according to any one of items 1 to 36, wherein the base material of the coated container comprises glass, preferably borosilicate glass or aluminoborosilicate glass, more preferably borosilicate glass.

[0146] 38. The composition of the glass is by mass % SiO2: 30-98%, preferably 50-90%, more preferably 70.0-74.0%, B2O3: 0-30%, preferably 3-20%, more preferably 7.0-16.0% Al2O3: 0-30%, preferably 1-15%, more preferably 3.0-6.5% X2O: 0-30%, preferably 1-15%, more preferably 2.0-7.2% (wherein X is selected from Na, K, and Li, preferably X is Na and / or K, more preferably Na), YO: 0-30%, preferably 0.1-5%, more preferably 0.5-1.0% (wherein Y is selected from Ca, Mg, and Ba, preferably Y is Ca and / or Mg), and Preferably unavoidable impurities A container comprising, preferably consisting thereof, the method, use and / or covered container according to any one of items 1 to 37.

[0147] 39. A coated container comprising, preferably according to any one of items 1 to 38, the substrate of the coated container comprising a polymer, preferably a cyclic olefin copolymer COC, and / or a cyclic olefin polymer COP, more preferably a cyclic olefin copolymer COC, and preferably consisting thereof.

[0148] 40. The base material of the coated container is • One or more compounds containing C, preferably one or more compounds containing C excluding compounds containing Si, and / or • One or more monomers, preferably norbornene, norbornane, and / or bicyclopentane, and / or • An antioxidant selected from the group consisting of one or more antioxidants, preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or dibutylhydroxytoluene (BHT); phosphytic antioxidants, more preferably tris(2,4-di-tert-butylphenyl)phosphytic antioxidants; phosphonite antioxidants, preferably tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diylbisphosphonite; and thioether antioxidants, more preferably phenolic antioxidants, more preferably pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. A container, preferably one of the methods, uses, and / or covered containers according to any one of items 1 to 39.

[0149] 41. A preferred method, use, and / or coated container according to any one of items 1 to 40, wherein the volume to the rim of the container is 0.1 ml to 1000 ml, preferably 0.5 ml to 500 ml, more preferably 1 ml to 250 ml, more preferably 2 ml to 30 ml, more preferably 3 ml to 15 ml, more preferably about 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 11 ml, 12 ml, 13 ml, 14 ml, or 15 ml, more preferably 5 to 15 ml.

[0150] 42. The method, use and / or coated container according to any one of items 1 to 41, wherein the coated container is a coated pharmaceutical container, more preferably a coated vial, a coated syringe, a coated ampoule or a coated cartridge, more preferably a coated vial.

[0151] 43. The covered container is a covered pharmaceutical container, preferably a cartridge or syringe, more preferably a syringe, wherein the smaller opening of the cartridge or syringe, preferably a syringe, is preferably closed with a tip cap and / or stopper, preferably the method, use and / or covered container according to any one of items 1 to 42.

[0152] 44. At least a portion of the coated surface, at least a portion of the alkali-treated surface, and at least a portion of the acid-treated surface are identical, and / or At least a portion of the coated surface includes at least a portion of the internal surface, preferably at least a portion of the coated surface is a surface that comes into contact with the solution when the coated container is placed upright on a flat surface and filled with a solution having a volume of 10% or more, preferably 30% or more, more preferably 90% or more, of the volume [volume / volume] up to the rim of the coated container, and / or At least a portion of the coated surface is a surface that comes into contact with the solution when the coated container is filled to a filling volume in accordance with ISO 4802-2:2016(E), Section 7.2. Preferably, the method, use, and / or covered container according to any one of items 1 to 43.

[0153] 45. A container whose substrate comprises one or more ions and / or compounds, preferably as described, used and / or coated according to any one of items 1 to 44.

[0154] 46. ​​i) A covered container, preferably a covered container as described in any one of items 1 to 45, and ii) A datasheet or storage medium containing quality evaluation results obtained by any one of the methods described in item 1 to 45. A kit that includes this. [Brief explanation of the drawing]

[0155] [Figure 1] This is a schematic side view of a surface that is at least partially covered. [Figure 2] This is a schematic side view of a surface that has been at least partially pre-treated and at least partially coated. [Figure 3] This is a schematic side view of an embodiment of the present invention. [Figure 4] This is a block diagram of a method according to an embodiment of the present invention. [Examples]

[0156] The present invention will be further explained below with reference to the following examples.

[0157] Example 1 Unless otherwise noted, Example 1 was prepared in accordance with European Patent Application Publication No. 0821079 (EP0821079 A1), European Patent Application Publication No. EP0811367 (EP0811367 A2), International Publication No. 03015122 (WO03015122 A1), and European Patent Application Publication No. 2106461 (EP2106461 A1): Two 10R vials (EVERIC® pure, manufactured by SCHOTT AG) were prepared. As an initial pretreatment, a washing pretreatment was performed, during which the vials were washed in a laboratory dishwasher (LS-2000, manufactured by HAMO AG) with ultrapure water having a pH of 10 μS / cm or less at 25°C for 2 minutes at room temperature, then for 6 minutes at 40°C, and subsequently for 25 minutes at room temperature. After that, the vials were dried at 300°C for 20 minutes.

[0158] Subsequently, the two vials were simultaneously treated and coated using the apparatus described in International Publication No. 03015122 (WO03015122 A1). Microwave irradiation with a frequency of 2.45 GHz was used for all plasma treatments. The reaction chamber was located inside the vials. The outside of the vials was dominated by ambient conditions.

[0159] First, the inside of the vials was evacuated to a pressure of 0.05 mbar. Then, oxygen was added to the vials to a pressure of 5 mbar (flow rate for both vials: 50 sccm), and then plasma pretreatment was started. The plasma was excited in pulse mode with an input power of 6700 W (for both vials), with a pulse duration of 0.5 ms and a pulse pause time of 1.8 ms. The plasma treatment was carried out for 14 seconds until the temperature of the vials reached 280°C, measured using a pyrometer at the center of the cylindrical portion of the vials.

[0160] The coating process was performed immediately afterward. The vials were filled with HMDSO (flow rate for both vials: 25 sccm) and the pressure was set to 0.8 mbar. The vials were then irradiated for 0.2 seconds (pressure: 0.8 mbar, flow rate for both vials: 25 sccm HMDSO, input power: 6000 W, pulse duration: 0.050 ms, pulse pause time: 30 ms), followed by irradiation for 50 seconds (pressure: 0.8 mbar, flow rate for both vials: 25 sccm HMDSO, input power: 3250 W, pulse duration: 0.003 ms, pulse pause time: 1 ms).

[0161] Subsequently, post-processing was performed, that is, the vials were filled with argon and cooled to room temperature in the presence of argon to obtain two equally coated vials.

[0162] Example 2 Unless otherwise noted, Example 2 was prepared in accordance with European Patent Publication No. 0821079, European Patent Publication No. EP0811367, International Publication No. 03015122, and European Patent Publication No. 2106461: Two 10R vials (EVERIC® pure, manufactured by SCHOTT AG) were prepared. As an initial pretreatment, a washing pretreatment was performed, during which the vials were washed in a laboratory dishwasher (LS-2000, manufactured by HAMO AG) with ultrapure water having a pH of 10 μS / cm or less at 25°C for 2 minutes at room temperature, then for 6 minutes at 40°C, and subsequently for 25 minutes at room temperature. After that, the vials were dried at 300°C for 20 minutes.

[0163] Subsequently, the two vials were simultaneously treated and coated using the apparatus described in International Publication No. 03015122 (WO03015122 A1). Microwave irradiation with a frequency of 2.45 GHz was used for all plasma treatments. The reaction chamber was located inside the vials. The outside of the vials was dominated by ambient conditions.

[0164] First, the inside of the vial was evacuated to a pressure of 0.05 mbar. Then, oxygen was added to the vial until a pressure of 1.2 mbar was reached (flow rate for both vials: 50 sccm), and then plasma treatment was initiated. The plasma was excited in pulse mode with an input power of 5500 W, with a pulse duration of 0.5 ms and a pulse pause time of 1.8 ms. After 27 seconds of plasma treatment, the temperature of the vial reached 280°C, as measured using a pyrometer at the center of the cylindrical portion of the vial.

[0165] The coating process was performed immediately afterward (11 seconds later). The vials were filled with HMDSO (flow rate for both vials: 25 sccm) and the pressure was set to 0.8 mbar. The vials were then irradiated for 0.2 seconds (pressure: 0.8 mbar, flow rate for both vials: 25 sccm HMDSO, input power: 6000 W, pulse duration: 0.050 ms, pulse pause time: 30 ms), followed by irradiation for another 11 seconds (pressure: 0.8 mbar, flow rate for both vials: 25 sccm HMDSO, input power: 4500 W, pulse duration: 0.008 ms, pulse pause time: 0.5 ms). After the coating process, the temperature of the vials was measured at the center of the cylindrical portion of the vials using a pyrometer and was 280°C.

[0166] Subsequently, post-processing was performed, that is, the vials were filled with oxygen and cooled to room temperature in the presence of oxygen, to obtain two equally coated vials.

[0167] Examples 3 and 4 Example 3 is a SCHOTT Top Lyo® 10R vial, and Example 4 is an uncoated SCHOTT Everic® pure 10R vial.

[0168] Method L described in this application i Table 1 shows the values ​​for Examples 1-4 obtained by this method.

[0169] [Table 1]

[0170] * o is the method for uncoated containers L i It is measured by [method].

[0171] Description of drawings and particularly preferred embodiments (items) There are several ways in which the teachings of the present invention may be advantageously designed and further developed. For this purpose, the following description of preferred examples of embodiments of the present invention illustrated by drawings should be referred to, on the one hand, to the claims dependent on the claims, and on the other hand to the claims dependent on the claims. With regard to the description of preferred embodiments of the present invention illustrated by drawings, generally preferred embodiments and further developments of the teachings will be described.

[0172] Figure 1: Schematic side view of a surface that is at least partially covered. Figure 2: Schematic side view of a surface that has been at least partially pre-treated and at least partially coated. Figure 3: Schematic side view of an embodiment of the present invention Figure 4: Block diagram of a method according to an embodiment of the present invention.

[0173] In the following description of embodiments, the same reference numerals indicate the same elements.

[0174] Explanation of the symbols 1. Glass surface 2 Coating 3. Pre-treated glass surface 4. External surface of the container 5. Inner surface of the container 6. Upper surface of the container crown 1001 Step of preparing the covered container 1002 A step of performing an alkali treatment on at least a portion of the coated surface of the coated container to obtain an alkali-treated surface. 1003 A step of performing an acid treatment on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, and 1004 A step of obtaining quality evaluation results by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface.

[0175] Figures 1 and 2 show schematic side views of embodiments of the present invention. In Figure 1, the glass surface 1 is partially covered with coating 2. The shown coating is a single layer coating. As a result, the coating is in direct contact with the glass surface 1 and is the outermost layer. In Figure 2, a partially pre-treated glass surface 3 is partially covered with coating 2. The shown coating is a single layer coating. As a result, the coating is in direct contact with the glass surface 1 and is the outermost layer. Figure 3 shows a schematic side view of an embodiment of the present invention. The outer surface 4 of the container is uncoated, and the inner surface 5 of the container is coated. The upper surface of the crown of the container does not belong to either the outer surface 4 or the inner surface 5 of the container, and is preferably uncoated.

[0176] Figure 4 shows a block diagram of a method according to an embodiment of the present invention. First, a coated container is prepared, which may or may not be heat-treated (1001). Then, an alkali treatment is performed on at least a portion of the coated surface of the coated container to obtain an alkali-treated surface (1002). Then, an acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution (1003). Finally, the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface is quantified to obtain a quality evaluation result (1004). [Explanation of Symbols]

[0177] 1. Glass surface 2 Coating 3. Pre-treated glass surface 4. External surface of the container 5. Inner surface of the container 6. Upper surface of the container crown 1001 Step of preparing the covered container 1002 A step of performing an alkali treatment on at least a portion of the coated surface of the coated container to obtain an alkali-treated surface. 1003 A step of performing an acid treatment on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution, and 1004 A step of obtaining quality evaluation results by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface.

Claims

1. A method for evaluating the quality of a coated container, comprising the following steps: - The stage of preparing the covered container, - A step of performing heat treatment on at least a portion of the covered container to obtain a heat-treated surface, - A step of performing an alkali treatment on at least a portion of the heat-treated surface to obtain an alkali-treated surface. - A step of performing acid treatment with an acid solution on at least a portion of the alkali-treated surface to obtain an acid-treated surface, and - A step of quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface to obtain quality evaluation results. Includes, At that time, Quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface to obtain quality evaluation results is equivalent to quantifying the content of one or more ions and / or compounds in the acid solution to obtain quality evaluation results. The aforementioned method.

2. The aforementioned alkaline treatment proceeds in the following steps: - A step of bringing an alkaline solution with a pH greater than 7 to 14 into contact with at least a portion of the heat-treated surface, - A step in which at least a portion of the alkali-treated surface is filled with ultrapure water and rinsed. The method according to claim 1, including the method described in claim 1.

3. The method according to claim 2, wherein one or more of the following conditions are met: i) The contact time between the alkaline solution and at least a portion of the heat-treated surface is 1 second to 1 week, and / or ii) The external pressure of the container is set to 0.1 bar to 10 bar, and / or iii) The temperature outside the container is set to 20°C to 200°C, and / or iv) The container is filled with the alkaline solution to a volume of [volume / volume], between 10% and 100%, relative to the volume up to the rim of the container, and / or v) The alkaline solution comprises water and a base, and / or vii) The container is kept closed during the alkali treatment.

4. The method according to any one of claims 1 to 3, wherein the heat treatment includes a step of tempering the container, and one or more of the following conditions are met: i) The tempering time is 1 minute to 1 day, and / or ii) The temperature outside the container during the tempering process is set to 25°C to the Tg of the container's substrate, and / or iii) The pressure during the tempering process is set to between 0.1 bar and 10 bar.

5. The method according to any one of claims 1 to 4, wherein the acid treatment includes the step of bringing an acid solution having a pH of less than 7 into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface.

6. The method according to any one of claims 1 to 5, wherein the acid treatment includes the step of bringing an acid solution into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface, wherein one or more of the following conditions are met: i) The contact time of the acid solution on at least a portion of the alkalized surface is 1 second to 1 week, and / or ii) The external pressure of the container is set to 0.1 bar to 10 bar, and / or iii) The temperature outside the container is set to 20°C to 200°C, and / or iv) The container is filled with the acid solution to a filling volume in accordance with ISO 4802-2:2016(E); Section 7.2, and / or v) The container is filled with the acid solution until it reaches a volume of [volume / volume] 10% to 100% of the volume up to the rim of the container, and / or vi) The acid solution comprises water and acid, and / or viiii) The acid solution contains an organic solvent and / or ix) The ratio [volume / volume] of water in the acid solution to the organic solvent is 0.1 to 10, and / or x) The container is kept closed during the acid treatment.

7. The method according to any one of claims 1 to 6, wherein obtaining a quality evaluation result by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface is equivalent to obtaining a quality evaluation result by quantifying the content of one or more ions in the acid solution.

8. To obtain quality evaluation results by quantifying the leaching of one or more ions and / or compounds from at least a portion of the acid-treated surface, the acid solution contains - One or more compounds containing C, and / or - One or more monomers, and / or • One or more antioxidants The method according to any one of claims 1 to 7, wherein the content of is quantified to obtain a quality evaluation result.

9. The following stages: - A step of evaluating the suitability of a covered container for storing a solution using the quality evaluation results obtained by the method according to any one of claims 1 to 8, and / or - A step of evaluating the stability of the coating of a coated container using the quality evaluation results obtained by the method according to any one of claims 1 to 8, and / or - A step of associating and / or linking the quality evaluation results obtained by the method of any one of claims 1 to 8 with the coated container, The method according to any one of claims 1 to 8, including the method described in any one of claims 1 to 8.

10. The following stages: - The step of manufacturing the first coated container and the second coated container using the same manufacturing method, - A step of obtaining a quality evaluation result for the first coated container by quantifying the leaching of the first coated container by the method described in any one of claims 1 to 9, and - A step of determining the suitability of the second covered container for storing the solution by applying and / or using the quality evaluation results of the first covered container, and / or using the quality evaluation results to quality control the first covered container and / or the second covered container, and / or - A step of determining the suitability of the second coated container for storing the solution by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits less than 90% leaching of one or more ions and / or compounds against the maximum limit in a hydrolysis resistance test of the container surface in accordance with ISO 4802-2:2016(E), Section 9.2, Classes HCF1 and HCF2, and / or - A step of determining the suitability of the second coated container for storing the solution by applying and / or using the quality evaluation results of the first coated container, wherein the first coated container exhibits leaching of one or more ions and / or compounds at a concentration of 10.00 mg / l or less. The method according to any one of claims 1 to 9, including the method described in any one of claims 1 to 9.

11. Use of quality evaluation results obtained by the method of any one of claims 1 to 10 for evaluating the suitability of a coated container for storing a solution, and / or for quality control of the manufacture of a coated container.

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