Test method for quality assessment and coated containers

Abstract

Disclosed are specific test methods for quality assessment and specific coated containers.

Description

Technical Field

[0001] This invention relates to a method for quality assessment of the adhesion of coatings on coated containers, particularly on container surfaces; and coated containers exhibiting improved stability over a wide pH range over extended periods. Background Technology

[0002] For decades, pharmaceutical compositions have been packaged in containers such as vials, ampoules, cartridges, or syringes. The high demands on containers have led to the continuous development of new materials for their use. However, the cost of further developing the body material of the container, such as glass compositions, outweighs the benefits, and to a certain extent, the material of the container cannot be further improved. To further improve the performance of the container, coatings can be applied, and various coatings are known, for example, as described in EP 0 821 079 and EP 0811 367.

[0003] If a pharmaceutical composition contains a highly sensitive drug, such as a biologic, it may be advantageous to store it in an alkaline buffer solution. However, to date, very time-consuming storage studies have been required to test whether containers coated under alkaline conditions are resistant to leaching and / or delamination, hindering rapid assessment of the suitability of containers for storage in alkaline solutions for sensitive drugs. Recognizing this problem, the inventors have developed a method for quality assessment of the adhesion of coatings, particularly on container surfaces, and for testing the chemical stability of container surfaces. This method is as follows:

[0004] - Fast; and / or

[0005] - Reliable; and / or

[0006] - Inexpensive; and / or

[0007] - Easy to do.

[0008] Furthermore, the inventors recognized the benefits of this method and used it to develop coated containers with improved performance, namely coated containers with the following properties:

[0009] - Excellent tolerance over a wide pH range; and / or

[0010] - Increased tolerance at high pH levels; and / or

[0011] - High chemical stability; and / or

[0012] - Excellent adhesion. Summary of the Invention

[0013] The above objective is achieved by a method for quality assessment of coated containers, comprising the following steps:

[0014] - Provide coated containers;

[0015] - At least a portion of the coated surface of the coated container is treated with alkali to obtain an alkali-treated surface;

[0016] - Acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a post-treatment acid solution; and

[0017] - Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

[0018] Furthermore, the above objective is achieved through a coated container, wherein the leaching of one or more types of ions and / or compounds is performed by the method described herein, preferably by the method described herein L. i Available, and the leaching of one or more types of ions and / or compounds is below 5.00 mg / L.

[0019] method

[0020] According to the present invention, a method for quality assessment of a coated container includes the following steps, preferably in this order:

[0021] - Provide coated containers;

[0022] - At least a portion of the coated surface of the coated container is treated with alkali to obtain an alkali-treated surface;

[0023] - Acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a post-treatment acid solution; and

[0024] - Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

[0025] In a (preferred) embodiment, the method includes the following steps, preferably in this order:

[0026] - Provide coated containers;

[0027] - Heat treatment is performed on at least a portion of the coated container to obtain a heat-treated surface;

[0028] - Perform alkali treatment on at least a portion of the heat-treated surface to obtain an alkali-treated surface;

[0029] - Acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a post-treatment acid solution; and

[0030] - Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

[0031] Due to the heat treatment, the coating is subjected to further stress, and the results of the quality assessment can identify coatings that are more heat-resistant.

[0032] In a preferred embodiment, the alkali treatment includes the following steps, preferably comprising:

[0033] - An alkaline solution with a pH >7 to 14, preferably 9 to 13, more preferably 9.5 to 12.5, and even more preferably about 11.7, is brought into contact with at least a portion of the surface of the coated container, preferably a heat-treated surface; and

[0034] - Preferably, the alkaline-treated surface is filled and rinsed with ultrapure water at least part of it, preferably two or more times, more preferably three times.

[0035] In particular, a pH of 9.0 or higher, preferably 9.5 or higher, is advantageous because at this high pH value, the coating is subjected to further stress, and thus the obtained quality assessment results reflect a more detailed perspective on the coating's performance in tolerating high pH values.

[0036] In a preferred embodiment, one or more of the following conditions are met:

[0037] i) The contact time between the alkaline solution and at least a portion of the coated and / or 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 more preferably about 3 hours; and / or

[0038] ii) Set the external pressure of the container to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably ambient pressure + about 1 bar; and / or

[0039] iii) Setting the external temperature of the container to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, and even more preferably about 121°C; and / or

[0040] iv) wherein the container is filled with 10% to 100%, preferably 30% to 95%, more preferably about 90% of its volume relative to its overflow volume [vol. / vol.]; and / or

[0041] v) The solution comprises water, preferably ultrapure water and an alkali, preferably an alkali, more preferably XOH (wherein X is selected from Na, K, Li), more preferably KOH, and preferably consists thereof; and / or

[0042] 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 about 0.005 mol / L; and / or

[0043] vii) wherein the container is preferably sealed by a sealing element, such as aluminum foil or a stopper, during alkali treatment.

[0044] If one or more of the above conditions i) to vii) are met, preferably all of the above conditions i) to vii), the coating is subjected to further stress, and thus the obtained quality assessment results reflect a more detailed perspective on the coating’s performance in tolerating high pH values.

[0045] In a preferred embodiment, one or more of the following conditions are met:

[0046] i) The contact time between the alkaline solution and at least a portion of the coated and / or heat-treated surface is 1 to 5 hours; and / or

[0047] ii) Set the external pressure of the container to 0.5 bar to 4 bar; and / or

[0048] iii) Set the external temperature of the container to 100°C to 150°C; and / or

[0049] iv) Where the container is filled with solution to approximately 90% of its volume relative to its overflow volume [vol. / vol.]; and / or

[0050] v) The solution consists of ultrapure water and alkali XOH (where X is selected from Na, K, Li), preferably KOH; and / or

[0051] vi) The concentration of the base is from 0.003 mol / L to 0.020 mol / L; and / or

[0052] vii) wherein the container is preferably sealed by a closed seal during alkali treatment.

[0053] In one embodiment, the contact time between the alkaline solution and at least a portion 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 about 3 hours. In one embodiment, the contact time between the alkaline solution and at least a portion of the coated surface and / or the heat-treated surface is more than 1 second, more than 1 minute, more than 1 hour, 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 the heat-treated surface is less than 1 week, less than 1 day, or less than 5 hours.

[0054] In one embodiment, the pressure outside the container is set to 0.1 bar to 10 bar, 0.5 bar to 4 bar, or ambient pressure plus about 1 bar. In one embodiment, the pressure outside the container is set to more than 0.1 bar, or more than 0.5 bar, or ambient pressure plus about 1 bar. In one embodiment, the pressure outside the container is set to less than 10 bar, or less than 4 bar.

[0055] 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 about 121°C. In another embodiment, the temperature outside the container is set to above 20°C, above 50°C, above 100°C, or about 121°C. In yet another embodiment, the temperature outside the container is set to below 200°C or below 150°C.

[0056] In one embodiment, the container is filled with the solution to 10% to 100%, 30% to 95%, or about 90% of its overflow volume. In one embodiment, the container is filled with the solution to more than 10% or more than 30% of its overflow volume. In one embodiment, the container is filled with the solution to less than 100% or less than 95% of its overflow volume.

[0057] In one embodiment, the solution comprises water, preferably ultrapure water, and an alkali, preferably a base, more preferably XOH (wherein X is selected from Na, K, Li), more preferably KOH, and preferably consists thereof. In one embodiment, the solution consists of ultrapure water and KOH as the alkali.

[0058] In one embodiment, the concentration of the base is from 0.0001 mol / L to 1 mol / L, preferably from 0.001 mol / L to 0.10 mol / L, more preferably from 0.003 mol / L to 0.020 mol / L, and even 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 less than 1 mol / L, less than 0.10 mol / L, or less than 0.020 mol / L.

[0059] In one embodiment, the container is preferably sealed during alkali treatment by a sealing seal, such as aluminum foil or a stopper.

[0060] In a preferred embodiment, the heat treatment includes the following steps, preferably comprising:

[0061] The container is tempered, preferably wherein one or more of the following conditions are met:

[0062] i) The tempering time is from 1 minute to 1 day, preferably from 30 minutes to 6 hours, more preferably about 60 minutes; and / or

[0063] ii) Setting the temperature outside the container during tempering to 25°C to the Tg of the container substrate, preferably 50°C to 500°C, more preferably 100°C to 400°C, more preferably 300°C to 400°C, and more preferably about 330°C; and / or

[0064] iii) Set the pressure during tempering to 0.1 bar to 10 bar, preferably ambient pressure.

[0065] If one or more of the above conditions i) to iii) are met, preferably all of conditions i) to iii), the coating is subjected to further stress, and thus the obtained quality assessment results reflect a more detailed perspective on the coating's resistance to high temperatures.

[0066] In a preferred embodiment, the heat treatment includes the following steps, preferably comprising:

[0067] The container is tempered, wherein the following conditions are met:

[0068] i) Tempering time is 30 minutes to 6 hours;

[0069] ii) Set the external temperature of the container to 300°C to 400°C during tempering; and

[0070] iii) Set the pressure during tempering to 0.1 bar to 10 bar, preferably ambient pressure.

[0071] In a preferred embodiment, the acid treatment includes the following steps, preferably comprising:

[0072] An acid solution with a pH of <7, preferably 0 to 6, preferably 0 to 3, more preferably 0 to 2, and even more preferably about 1 is brought into contact with a surface treated with at least a portion of an alkali to obtain an acid-treated surface and a treated acid solution.

[0073] In particular, a pH of 6 or lower, preferably 3 or lower, is advantageous because at this low pH value, the coating is subjected to further stress, and thus the obtained quality assessment results reflect a more detailed perspective on the coating's tolerance to low pH values.

[0074] In a preferred embodiment, the acid treatment includes the following steps, preferably comprising:

[0075] To obtain an acid-treated surface and a treated acid solution, the acid solution is brought into contact with at least a portion of the alkali-treated surface.

[0076] One or more of the following conditions must be met:

[0077] i) The contact time between the acid solution and at least a portion of the alkali-treated surface is from 1 second to 1 week, preferably from 1 minute to 1 day, more preferably from 1 hour to 10 hours, and more preferably about 6 hours; and / or

[0078] ii) Set the external pressure of the container to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably ambient pressure + about 1 bar; and / or

[0079] iii) Setting the external temperature of the container to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, and even more preferably about 121°C; and / or

[0080] iv) Wherein the container is filled with the solution to the filling volume according to section 7.2 of ISO 4802-2:2016(E); and / or

[0081] v) Wherein, relative to the overflow volume of the container [vol. / vol.], the container is filled with solution to reach 10% to 100%, preferably 30% to 95%, more preferably about 90% of its volume; and / or

[0082] vi) The solution comprises water, preferably ultrapure water, and an acid, preferably an acid, more preferably HX (wherein X is selected from F, Cl, Br, and / or I), more preferably HCl, and preferably consists of the above; and / or

[0083] 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, and even more preferably about 0.1 mol / L; and / or

[0084] viii) wherein the solution comprises an organic solvent, preferably an alcohol, an ester and / or an ether, more preferably an alcohol, more preferably an isopropanol; and / or;

[0085] ix) wherein the ratio of water to organic solvent [vol. / vol.] is 0.1 to 10, preferably 0.3 to 0.7, more preferably 0.4 to 0.6, and even more preferably about 0.5; and / or

[0086] x) Wherein the container is preferably sealed by a sealing element during acid treatment.

[0087] If one or more of the above conditions i) to x), preferably the above conditions i) to vii) and x), more preferably all of the above conditions i) to x), the coating is further subjected to stress, and thus the obtained quality assessment results reflect a more detailed perspective on the coating's performance in terms of tolerance to solutions with low pH values.

[0088] In one embodiment, the acid treatment includes the following steps:

[0089] An acid solution is brought into contact with at least a portion of a base-treated surface to obtain an acid-treated surface and a treated acid solution, wherein the following conditions are met:

[0090] i) The contact time between the acid solution and at least a portion of the alkali-treated surface is 1 hour to 10 hours, preferably about 6 hours;

[0091] ii) Set the external pressure of the container to ambient pressure + approximately 1 bar;

[0092] iii) Set the external temperature of the container to approximately 121°C;

[0093] iv) Wherein the container is filled with the solution to the filling volume according to ISO 4802-2:2016(E), section 7.2;

[0094] v) Where the volume of the container is filled to 90% of its capacity relative to the overflow volume [vol. / vol.].

[0095] vi) The solution consists of ultrapure water and HCl as an acid;

[0096] vii) The concentration of the acid is 0.1 mol / L;

[0097] viii) The solution contains isopropanol;

[0098] ix) where the ratio of water to organic solvent [vol. / vol.] is 0.5;

[0099] x) During acid treatment, the container is sealed by a closed seal.

[0100] In one embodiment of acid treatment, the contact time between the acid solution and at least a portion of the alkali-treated surface is from 1 second to 1 week, preferably from 1 minute to 1 day, more preferably from 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 more than 1 second, more than 1 minute, more than 1 hour, 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 less than 1 week, less than 1 day, or less than 10 hours.

[0101] In one embodiment of acid treatment, the pressure and temperature outside the container are set to 0.5 bar to 4 bar and 100°C to 150°C, ambient pressure + 1 bar and 100°C to 150°C, 0.5 bar to 4 bar and 121°C, or ambient pressure + 1 bar and approximately 121°C.

[0102] In one embodiment of acid treatment, the solution consists of ultrapure water and HCl as the acid. In another embodiment of acid treatment, the solution consists of ultrapure water and 0.1 mol / L HCl. In yet another embodiment of acid treatment, the solution consists of ultrapure water and 0.1 mol / L acid HX, wherein X is selected from F, Cl, and Br. In one embodiment of acid treatment, the solution consists of ultrapure water and 0.05 mol / L to 0.2 mol / L acid HX, wherein X is selected from F, Cl, and Br. In yet another embodiment of acid treatment, the solution contains water and 0.05 mol / L to 0.2 mol / L HCl.

[0103] In one embodiment of acid treatment, the container is filled with solution to 90% of its volume relative to its overflow volume [vol. / vol.].

[0104] In a preferred embodiment, the leaching of at least a portion of the acid-treated surface by one or more types of ions and / or compounds is quantified to obtain a quality assessment result. This is achieved by quantifying the content of one or more types of ions and / or compounds in the acid solution after quantification. Therefore, the leaching of one or more types of ions and / or compounds can be reliably determined, and this is a rapid and inexpensive method because no further extraction steps are required.

[0105] In another preferred embodiment, the leaching of at least a portion of the acid-treated surface by one or more types of ions and / or compounds is quantitatively determined to obtain a quality assessment result based on the content of one or more types of ions, preferably alkali metal ions, and more preferably Na ions, in the acid solution after quantitative treatment. Quantifying Na ions is particularly preferred if the container is a glass container and the container substrate includes Na, such as Na₂O. Therefore, in a preferred embodiment, the container is a glass container and the container substrate includes Na, such as Na₂O.

[0106] In another preferred embodiment, the leaching of at least a portion of the acid-treated surface by one or more types of ions and / or compounds is quantified to obtain a quality assessment result. The quality assessment result is then obtained by quantifying the content of the following substances in the acid solution after treatment:

[0107] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0108] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0109] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0110] If the container is a polymer container and the container substrate contains one or more monomers and / or preferably antioxidants, then a specific amount of one or more monomers and / or preferably antioxidants is particularly preferred. Therefore, in a preferred embodiment, the container is a polymer container and the container substrate contains one or more monomers and / or preferably antioxidants, preferably one of the aforementioned monomers and / or preferably antioxidants.

[0111] In a preferred embodiment, quantification is performed 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

[0112] Quantification was performed 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

[0113] Quantification was performed using titration.

[0114] These methods are particularly preferred because they allow for the reliable determination of the content of ions and / or compounds.

[0115] In one (preferred) embodiment, the method includes the following steps:

[0116] - Use the quality assessment results obtainable by the methods described herein to evaluate the suitability of the coated container for the storage solution, preferably a pharmaceutical solution; and / or

[0117] - The stability of the coating on the coated container, preferably a drug container, is evaluated using the quality assessment results obtainable through the methods described herein; and / or

[0118] - The quality assessment results obtainable by the methods described herein shall be associated with and / or related to the coated container, preferably the coated pharmaceutical container described herein.

[0119] If the method includes one or more of the steps described above, the quality assessment results are used to reduce complaints, thereby reducing costs. These steps can be performed at the plant where the containers are manufactured and / or tested; and / or these steps can be performed anywhere else, such as at the plant where the coated containers are filled or where the coated containers are sold and / or advertised.

[0120] In a (preferred) embodiment, the method includes the following steps, preferably in this order:

[0121] - The first and second coated containers are produced using the same production method;

[0122] -By the method according to any of the foregoing, preferably the method described herein L i Quantitative leaching of the first coated container is used to obtain a quality assessment result for the first coated container; and

[0123] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, and / or use the quality assessment results for the quality control of the first and / or second containers; and / or

[0124] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, wherein the first coated container exhibits, relative to the hydrolysis limit of Class 1 glass containers, one or more types of ions and / or compounds, more preferably, a leaching rate of Na ions <90%, preferably <50%, more preferably <30%; and / or

[0125] - The suitability of the second-coated container for the solution preferably stored in the second container is determined by applying and / or using the quality assessment results of the first-coated container, wherein the first-coated container exhibits, relative to the maximum limit in the hydrolysis resistance container surface test of ISO 4802-2:2016(E), Section 9.2, for HCF1 and HCF2 classes, the leaching of one or more types of ions and / or compounds, preferably <90%, preferably <50%, more preferably <30% of Na ions; and / or

[0126] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, wherein the first coated container exhibits leaching of one or more types of ions and / or compounds at a concentration of less than 10.00 mg / L, preferably less than 5.00 mg / L, more preferably less than 4.5 mg / L, more preferably less than 4.1 mg / L, more preferably less than 3.2 mg / L, more preferably less than 2.5 mg / L, more preferably less than 2.0 mg / L, more preferably less than 1.5 mg / L, more preferably less than 1.2 mg / L, more preferably less than 1.0 mg / L, more preferably less than 0.75 mg / L, more preferably less than 0.50 mg / L, more preferably less than 0.40 mg / L, more preferably less than 0.30 mg / L, more preferably less than 0.2 mg / L, more preferably less than 0.1 mg / L.

[0127] If the method includes one or more of the steps described above, the quality assessment results are used to reduce complaints, thereby reducing costs. These steps can be performed at the plant where the containers are manufactured and / or tested; and / or these steps can be performed anywhere else, such as at the plant where the coated containers are filled or where the coated containers are sold and / or advertised.

[0128] In one embodiment, the production of the first and second coated containers using the same manufacturing method includes...

[0129] - Provide first and second containers, wherein preferably, the first and second containers are glass containers, and the first and second containers each include a surface;

[0130] - A coating process is performed on at least a portion, preferably the inner surface, of the first and second containers, comprising the following steps:

[0131] a) The precursor P1 surrounds at least a portion of the surface, preferably the inner surface, of the first and second containers; and

[0132] b) Irradiate precursor P1 to generate plasma;

[0133] The same set of coating parameters is used for coating the first and second containers. The coating parameters are selected from process temperature PT1, pulse duration PD1, irradiation frequency of microwave generator, input power of microwave generator IP1, precursor P1, pulse irradiation, pulse pause time PP1 between two pulses, total irradiation time TT1, ratio of all pulse durations PD1 [μs] to all pulse pause times PP1 [ms] [μs / ms], process pressure PR1, process temperature reduction during coating process, and flow rate reduction of precursor P1.

[0134] In one embodiment, the method includes the following steps, preferably in this order:

[0135] - Provide containers with first and second coatings;

[0136] - The leaching of the first coated container is quantified by a leaching method to obtain the quality assessment results of the first coated container;

[0137] - Apply the quality assessment results of the first coated container to determine the suitability of the second coated container for the storage solution, or use the quality assessment results for the quality control of the second container.

[0138] In one embodiment, the method includes the following steps, preferably in this order:

[0139] - Provide containers with first and second coatings;

[0140] - The leaching of the first coated container is quantified by a leaching method to obtain the quality assessment results of the first coated container;

[0141] - Apply the quality assessment results of the first coated container to determine the suitability of the second coated container for the storage solution, or use the quality assessment results for the quality control of the second container;

[0142] The leaching method includes the following steps:

[0143] - Provide a container, preferably a coated container;

[0144] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0145] - Fill the drug container with 0.9 × (overflow volume) of 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%). (Merck), softened water (similar to ultrapure water with a purity of 1, ≤0.1 μS / cm at 25°C, as per DIN ISO 3696).

[0146] - Seal the container with a sealing material, such as aluminum foil or a stopper;

[0147] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0148] - Treat the container at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 3 hours;

[0149] - Open the sealing component;

[0150] - Empty the container;

[0151] - Fill and rinse the container twice with deionized water;

[0152] - If the container is a glass container: Fill the container with 0.9 × (overflow volume) of 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) diluted with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696), i.e., the same volume as used in the alkali treatment; or

[0153] - If the container is a polymer container: Fill the drug container with 0.9 × (overflow volume) 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) was diluted with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and isopropanol (1:1 / vol%:vol%), i.e., the same volume as that used in the alkali treatment.

[0154] - Seal the container with a sealing seal;

[0155] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0156] - Treat the container at 121°C and 1 bar above ambient pressure for 6 hours;

[0157] - Open the sealing component;

[0158] - If the container is a glass container: for example, use a Varian SpectrAA 280FS (PE 3-004) to analyze the content (mg / l) of one or more types of ions and / or compounds, preferably Na ions, in a 0.1 mol / l HCl solution by FAAS analysis to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably Na ions;

[0159] - If the container is a polymer container: for example, use a Waters I-Class UPLC system with Waters Xevo qTOF to analyze by LC-MS the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a 0.1 mol / l HCl solution to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0160] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0161] A*B / C,

[0162] Where A is the above-mentioned leaching value [mg / l] of one or more types of ions and / or compounds.

[0163] Where B is 0.9 × overflow volume, and

[0164] Where C is the wetted inner surface area of ​​the container (cm) 2 ); to obtain leaching values ​​[mg / cm³] of one or more types of ions and / or compounds, preferably Na ions or antioxidants. 2 ], which is the value of i.

[0165] In one embodiment, the method includes the following steps, preferably in this order:

[0166] - Provide containers with first and second coatings;

[0167] - The leaching of the first coated container is quantified by a leaching method to obtain the quality assessment results of the first coated container;

[0168] - Apply the quality assessment results of the first coated container to determine the suitability of the second coated container for the storage solution, or use the quality assessment results for the quality control of the second container;

[0169] The leaching method includes the following steps:

[0170] - Provide a container, preferably a coated container;

[0171] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0172] - Fill the drug container with 0.9 × (overflow volume) of 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%). (Merck), softened water (similar to ultrapure water of purity 1 with a purity of ≤0.1μS / cm at 25°C according to DIN ISO 3696);

[0173] - Seal the container with a sealing material, such as aluminum foil or a stopper;

[0174] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0175] - Treat the container at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 3 hours;

[0176] - Open the sealing component;

[0177] - Empty the container;

[0178] - Fill and rinse the container twice with deionized water;

[0179] - Fill the drug container with 0.9 × (overflow volume) of 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) is diluted with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696), i.e., the same volume as that used in the alkali treatment;

[0180] - Seal the container with a sealing seal;

[0181] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0182] - Treat the container at 121°C and 1 bar above ambient pressure for 6 hours;

[0183] - Open the sealing component;

[0184] - Empty the container;

[0185] - Fill and rinse the container twice with deionized water;

[0186] - Preferably, an air-dried container is used;

[0187] - Fill the drug container with 0.9 × (overflow volume) of n-hexane, which is the same volume used in the alkali treatment;

[0188] - Shake the drug container in a fixed-track shaker (80 rpm) for 30 minutes at room temperature;

[0189] - For example, using a Waters I-Class UPLC system with Waters Xevo qTOF, the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a hexane solution is analyzed by LC-MS to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0190] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0191] A*B / C,

[0192] Where A is the above-mentioned leaching value [mg / l] of one or more types of ions and / or compounds, where B is 0.9 × overflow volume, and where C is the wetted inner surface area of ​​the container (cm). 2); to obtain leaching values ​​[mg / cm³] of one or more types of ions and / or compounds, preferably Na ions or antioxidants. 2 ], which is the value of i.

[0193] In one embodiment, the method includes the following steps, preferably in this order:

[0194] - Provide containers with first and second coatings;

[0195] - The leaching of the first coated container is quantified by a leaching method to obtain the quality assessment results of the first coated container;

[0196] - Apply the quality assessment results of the first coated container to determine the suitability of the second coated container for the storage solution, or use the quality assessment results for the quality control of the second container;

[0197] The leaching method includes the following steps:

[0198] - Provides a preferred method for L described above i The same container;

[0199] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0200] - Fill the drug container with 0.9 × (overflow volume) of solution;

[0201] - Seal the container with a sealing seal;

[0202] - Insert the container into the beaker, such as a stainless steel or aluminum beaker;

[0203] - Use 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%) (Merck), fill the beaker with softened water (similar to ultrapure water of purity 1 with a purity of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) until the same level as the liquid in the container is reached;

[0204] - Seal the beaker with a sealing device;

[0205] - Insert the beaker into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0206] - Treat the beaker at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 3 hours;

[0207] - Open the sealing part of the beaker;

[0208] - Empty the beaker;

[0209] - Fill and rinse the beaker twice with deionized water, and clean the exterior of the container by rinsing the outer surface with deionized water;

[0210] - Insert the container back into the beaker, such as a stainless steel or aluminum beaker;

[0211] - If the container is a glass container: use a 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) Dilute with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and fill the beaker until it reaches the same level as the liquid in the container, i.e., the same volume as used in the alkali treatment, or

[0212] - If the container is a polymer container: use a 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) Fill the beaker with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and isopropanol (1:1 / vol%:vol%) until the liquid level is the same as that in the container, i.e. the same volume used in the alkali treatment.

[0213] - Seal the beaker with a sealing device;

[0214] - Insert the beaker into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0215] - Treat the beaker at 121°C and 1 bar above ambient pressure for 6 hours;

[0216] - Open the beaker;

[0217] - If the container is a glass container: For example, use a Varian SpectrAA 280FS (PE 3-004) to analyze the content (mg / l) of one or more types of ions and / or compounds, preferably Na ions, in a 0.1 mol / l HCl solution by FAAS analysis to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably Na ions;

[0218] - If the container is a polymer container: for example, use a Waters I-Class UPLC system with Waters Xevo qTOF to analyze by LC-MS the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a 0.1 mol / l HCl solution to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0219] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0220] A*B / C,

[0221] Where A is the above-mentioned leaching value [mg / L] of one or more types of ions and / or compounds, where B is the volume of the solution in the beaker, and where C is the wetted outer surface area of ​​the container (cm). 2 ); to obtain leaching values ​​[mg / cm³] for one or more types of ions and / or compounds. 2 ], which is the o value.

[0222] In a preferred embodiment, the method includes the step of filling a coated container with a solution, preferably a pharmaceutical composition, more preferably a pharmaceutical solution with a pH of 4 to 14, preferably a pH > 7 to 12, and more preferably a pH of 9 to 11. In a preferred embodiment, the pharmaceutical composition includes one or more compounds expressly mentioned in WO2018 / 157097A1, which is incorporated herein by reference.

[0223] One embodiment of the invention is to use quality assessment results obtainable by the methods described herein to evaluate the suitability of coated containers, preferably coated pharmaceutical containers, for storing solutions, preferably pharmaceutical solutions, and / or the quality control of the production of coated containers. Using the quality assessment results reduces complaints, thereby lowering costs. The quality assessment results can be used at the plant where the containers are produced and / or tested; and / or in any other place, such as at the plant where the coated containers are filled or where the coated containers are sold and / or advertised.

[0224] Coated container

[0225] One embodiment of the invention is a coated container in which leaching of one or more types of ions and / or compounds is performed by the methods described herein, preferably by the methods described herein. i Available, and the leaching of one or more types of ions and / or compounds is below 5.00 mg / L.

[0226] In a (preferred) embodiment, the method described herein, preferably the method described herein L i The leaching of one or more types of ions and / or compounds is less than 10.00 mg / L, preferably less than 5.00 mg / L, more preferably less than 4.5 mg / L, more preferably less than 4.1 mg / L, more preferably less than 3.2 mg / L, more preferably less than 2.5 mg / L, more preferably less than 2.0 mg / L, more preferably less than 1.5 mg / L, more preferably less than 1.2 mg / L, more preferably less than 1.0 mg / L, more preferably less than 0.75 mg / L, more preferably less than 0.50 mg / L or less, more preferably less than 0.40 mg / L or less, more preferably less than 0.30 mg / L or less, more preferably less than 0.2 mg / L, and more preferably less than 0.1 mg / L. Therefore, tolerance over a wide pH range, especially at high pH values, can be further improved.

[0227] In one (preferred) embodiment, the method described herein, preferably the method described herein, is used to achieve the maximum limit relative to the maximum value limit in the hydrolysis resistance test of HCF1 and HCF2 class containers according to ISO 4802-2:2016(E), Section 9.2. i The leaching of one or more types of ions and / or compounds is less than 100%, preferably less than 90%, more preferably less than 50%, and even more preferably more than 1% to less than 30%. Therefore, tolerance over a wide pH range, especially at high pH values, can be further improved.

[0228] In a (preferred) embodiment, the method described herein, preferably the method described herein L i The leaching of one or more types of ions and / or compounds that are available is called a;

[0229] Where a ≤ b*c;

[0230] If 0.9 × the container's (overflow volume) ≤ 1 ml, then b is 5.00 mg / l.

[0231] If 0.9 × the container's (overflow volume) > 1 ml and ≤ 2 ml, then b is 4.50 mg / L.

[0232] If 0.9 × the container's (overflow volume) > 2 ml and ≤ 3 ml, then b is 4.10 mg / L.

[0233] If 0.9 × the container's (overflow volume) > 3 ml and ≤ 5 ml, then b is 3.20 mg / L.

[0234] If 0.9 × the container's (overflow volume) > 5 ml and ≤ 10 ml, then b is 2.50 mg / L.

[0235] If 0.9 × the container's (overflow volume) > 10 ml and ≤ 20 ml, then b is 2.00 mg / L.

[0236] If 0.9 × the container's (overflow volume) > 20 ml and ≤ 50 ml, then b is 1.50 mg / L.

[0237] If 0.9 × container's (overflow volume) > 50 ml and ≤ 100 ml, then b is 1.20 mg / L.

[0238] If 0.9 × the container's (overflow volume) > 100 ml and ≤ 200 ml, then b is 1.00 mg / L.

[0239] If 0.9 × container (full capacity) > 200 ml and ≤ 500 ml, then b is 0.75 mg / L; and

[0240] If 0.9 × the container's (overflow volume) > 500 ml, then b is 0.50 mg / L; and

[0241] Wherein 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. Since leaching depends on the size of the container (see ISO 4802-2:2016(E)), the above parameters are preferred, especially for very small and large containers. Meeting these parameters further improves tolerance over a wide pH range, particularly high pH values. In yet another 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, more preferably 0.2 mg / L or more.

[0242] In one (preferred) embodiment, the coated container includes an inner surface and an outer surface, wherein at least a portion of the inner surface is covered by the coating; and

[0243] The coated container exhibits the following equation:

[0244] i / o≤d

[0245] d value ([mg / cm2] / [mg / cm2]) 2 The value is 0.90.

[0246] Where i is the method described herein, preferably L is the method described herein. i Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 );and

[0247] Where o is the leaching (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 ) and / or through the methods described herein L o Available. If this parameter is met, the protection of the pharmaceutical composition stored inside the container is improved, particularly compared to the same but uncoated container. Since most known coatings for containers are completely intolerant of alkali and acid treatments, this is part of the method described herein and is also part of the method L described herein. i As part of this, if the above parameters are met, the coating of the coated container exhibits excellent tolerance to solutions with high or low pH values.

[0248] In one embodiment, the coated container includes an inner surface and an outer surface, wherein at least a portion of the inner surface is coated with a coating; and

[0249] The coated container exhibits the following equation:

[0250] i / o≤d

[0251] d value ([mg / cm) 2 ] / [mg / cm 2 The value is 0.90.

[0252] Where i is obtained through method L i One or more types of ionic and / or compound leaching available (mg / cm³) 2 );and

[0253] Where o is the leaching (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 And through method L o Available.

[0254] In one embodiment, the coated container includes an inner surface and an outer surface, wherein at least a portion of the inner surface is coated with a coating; and

[0255] The coated container exhibits the following equation:

[0256] i / o≤d

[0257] d value ([mg / cm) 2 ] / [mg / cm 2 The value is 0.90.

[0258] Where i is obtained through method L i One or more types of ionic and / or compound leaching available (mg / cm³) 2 );and

[0259] Where o is the leaching (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 And through method L o Available

[0260] Among them, through method L i One or more types of ions and / or compounds are available, and one or more types of ions and / or compounds are present in the substrate of the coated container, and by method L o What is available are the same kind of ions and / or compounds.

[0261] In yet another 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. Therefore, the protection of the pharmaceutical composition stored inside the container is further improved.

[0262] In one (preferred) embodiment, the coated container exhibits the following equation:

[0263] i / o≥e

[0264] e value ([mg / cm) 2 ] / [mg / cm 2 The value 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.

[0265] In yet another preferred embodiment, i is 1.0 * 10 -10 mg / cm 2 Up to 1.0*10 -3 mg / cm 2 Preferably 1.0*10 - 8 mg / cm 2 Up to 6.5*10 -4 mg / cm 2 More preferably 1.0*10 -7 mg / cm 2 Up to 6.0*10 -4 mg / cm 2 More preferably 1.0*10 - 6 mg / cm 2Up to 3.0*10 -4 mg / cm 2 More preferably 7.0*10 -6 mg / cm 2 Up to 3.0*10 -5 mg / cm 2 Therefore, the protection of the pharmaceutical composition stored inside the container is further enhanced.

[0266] In yet another preferred embodiment, o is 1.1 * 10⁻⁶. -5 mg / cm 2 Up to 1.0*10 -1 mg / cm 2 Preferably 1.0*10 -4 mg / cm 2 Up to 1.0*10 -2 mg / cm 2 More preferably 6.5*10 -4 mg / cm 2 Up to 1.0*10 -3 mg / cm 2 More preferably 6.8*10 -4 mg / cm 2 Up to 7.5*10 -4 mg / cm 2 The lower the O value, the better the resistance of the container's substrate. Therefore, the lower the O value, the better the protection of the pharmaceutical composition stored inside the container.

[0267] In yet another preferred embodiment, i is achieved by the method described herein L i Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 ); and / or o is the method described herein L o Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 Therefore, the values ​​of i and o can be reliably determined, and only one container is needed to determine these two parameters. Method L can also be used if the outer surface is coated with, for example, a silicone coating or another coating available through PICVD coating. o Preferably, if method L is used... o If so, the outer surface is not coated.

[0268] In yet another preferred embodiment, o is the leaching of one or more types of ions and / or compounds from an uncoated container (mg / cm³). 2The uncoated container can be obtained by the same production method as the coated container (however, without coating), wherein o can be obtained by the methods described herein and / or by the methods described herein L i It is available. Therefore, the values ​​of o and i can be reliably determined using only one method.

[0269] In yet another preferred embodiment, one or more types of 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. Quantification of Na ions is particularly preferred if the container is a glass container and the container substrate comprises sodium, such as Na₂O. Therefore, in a preferred embodiment, the container is a glass container and the container substrate comprises sodium, such as Na₂O.

[0270] In yet another preferred embodiment, one or more types of ions and / or compounds are:

[0271] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0272] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0273] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0274] In a preferred embodiment, the container is a polymer container and the substrate of the container contains one or more antioxidants and / or preferably monomers.

[0275] There are no particular limitations on the coating method used to obtain the coated container. In another preferred embodiment, the coating is obtained by a coating method, preferably a CVD method, more preferably a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma-pulsed chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably a plasma-pulsed chemical vapor deposition (PICVD) method. This method is particularly suitable for applying coatings that exhibit excellent tolerance over a wide pH range, improved tolerance at high pH values, high chemical stability, and excellent adhesion.

[0276] In another preferred embodiment, the coating is a coating obtainable by a pretreatment and coating method, preferably a CVD method, more preferably a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma-pulsed chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably a plasma-pulsed chemical vapor deposition (PICVD) method, wherein the pretreatment is performed prior to the coating method. This method is particularly suitable for applying coatings and further improving tolerance over a wide pH range and at high pH values, and further improving chemical stability and adhesion.

[0277] In yet another preferred embodiment, the coating method includes the following steps:

[0278] - Provide a container, preferably a glass container, including a surface;

[0279] - A coating process is performed on at least a portion, preferably the inner surface, of the container, comprising the steps of:

[0280] a) Enclosing at least a portion, preferably the inner surface, of the container through the precursor P1; and

[0281] b) Irradiate precursor P1 to generate plasma;

[0282] Wherein at least one, preferably all, of the following parameters are satisfied:

[0283] i) wherein the process temperature PT1 is 200°C to the Tg of the glass element, preferably 200°C to 500°C, more preferably 220°C to 450°C, more preferably 240°C to 320°C, and more preferably 250°C to 300°C; and / or

[0284] ii) wherein the plasma pulse duration PD1 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 or less; and / or

[0285] iii) wherein the plasma pulse duration PD1 is 0.1 μs or more, preferably 0.5 μs or more, more preferably 1 μs or more, and even more preferably 6 μs or more; and / or

[0286] iv) wherein the irradiation is performed by a microwave generator, preferably wherein the radiation has 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, and more preferably about 2.45 GHz; and / or

[0287] v) wherein the input power IP1, preferably the microwave generator's input power IP1 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

[0288] vi) wherein the precursor P1 comprises one or more of hexamethyldisiloxane (HMDSO), hexamethyldisilazane (HMDS), tetramethylsilane (TMS), trimethylborazole (TMB), tris(dimethylaminosilyl)-amino-di(dimethylamino)borane (TDADB), tris(trimethylsilane)borate (TMSB), hexamethylcyclotrisiloxane (HMCTSO), octamethylcyclotetrasiloxane (OMCTS), decamethylcyclopentasiloxane (DMCPS), dodecylcyclohexasiloxane (DMCHS), diacetoxy-di-tert-butoxysilane (DADBS), tetraethoxysilane (TEOS), tris(trimethylsiloxy)vinylsilane (TTMSVS), and vinyltriethoxysilane (VTES) and / or combinations thereof, preferably the precursor P1 is HMDSO; and / or

[0289] vii) wherein the precursor P1 comprises elements Si, C, O, and H, preferably composed of them; and / or

[0290] 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

[0291] 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

[0292] x) The ratio of all pulse durations PD1 [μs] to all pulse pause times PP1 [ms] [μs / ms] is 1 or more, preferably 2 or more, more preferably 2 to 50, more preferably 3 to 8; and / or

[0293] xi) wherein 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, and more preferably about 0.8 mbar; and / or

[0294] xii) wherein the process temperature decreases, preferably decreases steadily, during the coating process; and / or

[0295] xiii) wherein the process temperature PT1 is at least partially, preferably at least 220°C, preferably at least 240°C, more preferably at least 250°C, more preferably at least 255°C, more preferably at least 270°C, and more preferably at least 280°C; and / or

[0296] xiv) wherein the flow rate of precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and even more preferably 10 to 15 sccm.

[0297] Preferably, all of the above parameters are satisfied. This method is particularly suitable for applying coatings and further improving tolerance over a wide pH range and at high pH values, as well as further improving chemical stability and adhesion.

[0298] In one embodiment, the coating process is performed in an apparatus according to WO 03 015 122 A1.

[0299] In one embodiment, surrounding at least a portion of the surface, preferably the inner surface, of the container with the precursor P1 can be understood as exposing at least a portion of the surface, preferably the inner surface, of the container to the precursor P1.

[0300] In one embodiment, surrounding at least a portion of the surface, preferably the inner surface, of the container with the precursor P1 can be understood as subjecting at least a portion of the surface, preferably the inner surface, of the container to the precursor P1.

[0301] In one embodiment of the method, the flow rate of precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and even more preferably 10 to 15 sccm. More preferably, precursor P1 is chemically pure, with a purity of at least 99 wt.%.

[0302] In yet another preferred embodiment, the pretreatment is a plasma pretreatment comprising the following steps:

[0303] - Provide a container, preferably a glass container, including a surface;

[0304] - A coating process is performed on at least a portion, preferably the inner surface, of the container, comprising the following steps:

[0305] a) The precursor P2 surrounds at least a portion, preferably the inner surface, of the container; and

[0306] b) Irradiate precursor P2 to generate plasma;

[0307] Wherein at least one, preferably all, of the following parameters are satisfied:

[0308] i) wherein the process temperature PT2 is from room temperature to the Tg of the glass element, preferably from room temperature to 450°C, more preferably from room temperature to 400°C, more preferably from room temperature to 320°C, and more preferably from room temperature to about 280°C; and / or

[0309] ii) wherein the plasma pulse duration PD2 is less than 50 ms, preferably less than 40 ms, preferably less than 30 ms, more preferably less than 20 ms, more preferably less than 15 ms, more preferably less than 8 ms, more preferably less than 6 ms, more preferably less than 1 ms, and more preferably about 0.5 ms; and / or

[0310] iii) wherein the plasma pulse duration PD2 is 0.1 ms or more, preferably 0.2 ms or more, more preferably 0.3 ms or more, and even more preferably 0.5 ms or more; and / or

[0311] iv) wherein the irradiation is performed by a microwave generator, preferably wherein the radiation has 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, and more preferably about 2.45 GHz; and / or

[0312] v) wherein the input power IP2, preferably the microwave generator's input power IP2 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

[0313] vi) Precursor P2 includes argon, oxygen and / or nitrogen, preferably oxygen, more preferably air; and / or

[0314] vii) wherein the precursor P2 comprises element N (e.g., N2) and / or O (e.g., element O2), preferably N2 and O2, more preferably O2, and preferably composed thereof; and / or

[0315] 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, and more preferably about 1.8 ms; and / or

[0316] 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

[0317] x) The ratio of all pulse durations PD2 [ms] to all pulse pause times PP2 [ms] [ms / ms] is 0.05 or more, preferably 0.1 or more, more preferably 0.15 to 5, more preferably 0.2 to 0.5; and / or

[0318] xi) wherein 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

[0319] xii) wherein the process temperature PT2 increases, preferably steadily, during plasma pretreatment; and / or

[0320] xiii) wherein the process temperature PT2 is at least partially, preferably at least 220°C, preferably at least 240°C, more preferably at least 250°C, more preferably at least 255°C, more preferably at least 270°C, and more preferably at least about 280°C at the end of the plasma pretreatment process; and / or

[0321] xiv) wherein the flow rate of precursor P2 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 50 sccm, and even more preferably 20 to 30 sccm.

[0322] This method is particularly suitable for pretreating surfaces and further improving tolerance over a wide pH range and at high pH values, as well as further enhancing chemical stability and adhesion.

[0323] In one embodiment, surrounding at least a portion of the surface, preferably the inner surface, of the container with the precursor P2 can be understood as exposing at least a portion of the surface, preferably the inner surface, of the container to the precursor P2.

[0324] In one embodiment, surrounding at least a portion of the surface, preferably the inner surface, of the container with the precursor P2 can be understood as subjecting at least a portion of the surface, preferably the inner surface, of the container to the precursor P2.

[0325] In yet another preferred embodiment, the inner surface of the container, preferably the entire inner surface of the container, is coated. This further protects the pharmaceutical composition. In yet another preferred embodiment, the outer surface of the container is not coated. In yet another 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. This further protects the pharmaceutical composition. If the outer surface is not coated, leaching of one or more types of ions and / or compounds can preferably be similar to, preferably equivalent to, leaching of the substrate of the container. More preferably, the coating can be obtained as described in European patent application EP 21 164 784, which is incorporated herein by reference.

[0326] In yet another preferred embodiment, the substrate of the coated container comprises glass, preferably borosilicate glass or aluminoborosilicate glass, more preferably borosilicate glass, and is preferably composed thereof. In yet another preferred embodiment, the glass comprises, by weight percent, the following components, and is preferably composed thereof:

[0327] SiO2: 30-98%, preferably 50-90%, more preferably 70.0-74.0%;

[0328] B2O3: 0-30%, preferably 3-20%, more preferably 7.0-16.0%;

[0329] Al2O3: 0-30%, preferably 1-15%, more preferably 3.0-6.5%;

[0330] X2O: 0-30%, preferably 1-15%, more preferably 2.0-7.2%, wherein X is selected from Na, K, Li, preferably Na and / or K, more preferably Na;

[0331] YO: 0-30%, preferably 0.1-5%, more preferably 0.5-1.0%, wherein Y is selected from Ca, Mg, Ba, and preferably Y is Ca and / or Mg; and

[0332] Preferably, the unavoidable impurities are less than 5 wt.%, more preferably less than 2.5 wt.%, more preferably less than 1.0 wt.%, more preferably less than 0.5 wt.%, more preferably less than 0.1 wt.%, more preferably less than 0.01 wt.%; and / or, preferably, the impurities are selected from Fe, Ti, Zn, Cu, Mn, and Co.

[0333] In yet another preferred embodiment, the substrate of the coated container comprises a polymer, preferably a cyclic olefin copolymer (COC) and / or a cyclic olefin polymer (COP), more preferably a cyclic olefin copolymer (COC), and is preferably composed thereof. Preferably, the polymer comprises an antioxidant.

[0334] In yet another preferred embodiment, the substrate of the coated container includes:

[0335] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0336] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0337] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0338] In another preferred embodiment, the overflow volume 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 another preferred embodiment, the coated container is a coated drug container, more preferably a coated vial, a coated syringe, a coated ampoule or a coated cartridge, more preferably a coated vial. In yet another preferred embodiment, the coated container is a coated drug container, preferably a cartridge or syringe, preferably a syringe, wherein the smaller opening of the cartridge or syringe, preferably the syringe, is preferably closed by a cap and / or a stopper. In yet another 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 inner surface, preferably at least a portion of the coated surface being the surface in contact with the solution when the coated container is standing upright on a flat surface and filled with at least 10%, preferably at least 30%, more preferably at least 90%, more preferably 90% of the volume of solution relative to the overflow volume [vol. / vol.] of the coated container; and / or at least a portion of the coated surface being the surface in contact with the solution when the coated container is filled to the filling volume according to ISO 4802-2:2016(E), section 7.2. If one or more of the above parameters are satisfied, the safety of the pharmaceutical composition during storage in the coated container can be further improved.

[0339] In a preferred embodiment, the substrate of the container comprises one or more types of ions and / or compounds. Therefore, the reliable determination of the values ​​described herein can be improved.

[0340] One embodiment of the present invention is a reagent kit, comprising:

[0341] i) Preferably, a coated container as described herein, and

[0342] ii) A data table or storage medium that includes quality assessment results obtainable through the methods described herein.

[0343] definition

[0344] The contact time described herein is the time that the composition, such as an acidic composition, is in contact with at least a portion of the surface. Contact time does not include the time spent preparing the sample or preparing the sample for the next step. Contact time may also be the time the sample spends in an autoclave, which is being operated and set to a specific pressure and temperature.

[0345] In this paper, the heat-treated surface is a coated surface that has already undergone heat treatment. The substrate is the uncoated material of the container, such as glass or polymer. The ambient pressure and temperature are the pressures and temperatures measured during the process, such as 1 bar and 20°C.

[0346] In this document, an acidic composition is a composition comprising an acid, such as HCl, and a solvent, such as water and / or an organic solvent, preferably thereof.

[0347] Unless otherwise stated, ratios in this article always refer to volume ratios, i.e., [vol. / vol.].

[0348] In this document, monomers are monomers already used to produce substrates for coated containers, which comprise, and preferably consist of, polymers. Since industrial production methods for polymers are well-known, those skilled in the art can readily deduce the corresponding monomers from the polymers. Well-known monomers are, for example, substituted or unsubstituted, preferably unsubstituted, norbornene, norbornene, and / or bicyclopentane.

[0349] Unavoidable impurities in this document are those that may be contained in the segregated 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 less than 5 wt.%, preferably less than 2.5 wt.%, more preferably less than 1.0 wt.%, more preferably less than 0.5 wt.%, more preferably less than 0.1 wt.%, and more preferably less than 0.01 wt.%.

[0350] In this paper, the total irradiation time is the sum of all pulse durations and pulse pause times.

[0351] In this article, the temperature during the pretreatment and coating processes refers to the temperature measured in the middle of the glass element using a pyrometer. In the case of a container with a cylindrical portion, the temperature during the coating process is measured in the middle of the cylindrical portion of the container, such as a vial.

[0352] Unless otherwise specified, the input power is the positive power measured between the irradiation generator, such as a microwave generator, and the glass element, for example, by a MW diode (ACTP-1502; 10dB attenuation).

[0353] In this paper, Tg (glass transition temperature) was measured by differential scanning calorimetry (DSC).

[0354] Ultrapure water is water with a purity of 1, similar to DIN ISO 3696, which is ≤0.1 μS / cm at 25°C.

[0355] Even though the methods described herein for quality assessment refer to coated containers, those skilled in the art will recognize that these methods can also be applied to uncoated containers, for example, to obtain reference values. Unless otherwise stated, overflow volume herein refers to the overflow volume of the container, preferably a coated container.

[0356] Parameters and methods

[0357] The value of i can be obtained as described herein. Preferably, i is obtained through the following method L i Sure.

[0358] Method L i

[0359] Here, a particularly preferred embodiment of the present invention is the following method (method L) i ), including the following steps:

[0360] - Provide a container, preferably a coated container;

[0361] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0362] - Fill the drug container with 0.9 × (overflow volume) of 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%). (Merck), softened water (similar to ultrapure water of purity 1 with a purity of ≤0.1μS / cm at 25°C according to DIN ISO 3696);

[0363] - Seal the container with a sealing material, such as aluminum foil or a stopper;

[0364] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0365] - Treat the container at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 3 hours;

[0366] - Open the sealing component;

[0367] - Empty the container;

[0368] - Fill and rinse the container twice with deionized water;

[0369] - If the container is a glass container: Fill the container with 0.9 × (overflow volume) of 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) diluted with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696), i.e., the same volume as used in the alkali treatment, or

[0370] - If the container is a polymer container: Fill the drug container with 0.9 × (overflow volume) 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) was diluted with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and isopropanol (1:1 / vol%:vol%), i.e., the same volume as used in the alkali treatment.

[0371] - Seal the container with a sealing seal;

[0372] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0373] - Treat the container at 121°C and 1 bar above ambient pressure for 6 hours;

[0374] - Open the sealing component;

[0375] - If the container is a glass container: for example, use a Varian SpectrAA 280FS (PE 3-004) to analyze the content (mg / l) of one or more types of ions and / or compounds, preferably Na ions, in a 0.1 mol / l HCl solution by FAAS analysis to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably Na ions;

[0376] - If the container is a polymer container: for example, use a Waters I-Class UPLC system with Waters Xevo qTOF to analyze by LC-MS the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a 0.1 mol / l HCl solution to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0377] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0378] A*B / C,

[0379] Where A is the above-mentioned leaching value [mg / l] of one or more types of ions and / or compounds.

[0380] Where B is 0.9 × overflow volume, and

[0381] Where C is the wetted inner surface area of ​​the container (cm) 2); to obtain leaching values ​​[mg / cm³] of one or more types of ions and / or compounds, preferably Na ions or antioxidants. 2 ], which is the value of i.

[0382] Alternative embodiments include a method (method L) i It includes the following steps:

[0383] - Provide a container, preferably a coated container;

[0384] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0385] - Fill the drug container with 0.9 × (overflow volume) of 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%). (Merck), softened water (similar to ultrapure water of purity 1 with a purity of ≤0.1μS / cm at 25°C according to DIN ISO 3696);

[0386] - Seal the container with a sealing material, such as aluminum foil or a stopper;

[0387] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0388] - Treat the container at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 6 hours;

[0389] - Open the sealing component;

[0390] - Empty the container;

[0391] - Fill and rinse the container twice with deionized water;

[0392] - Fill the drug container with 0.9 × (overflow volume) of 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) is diluted with softened water (similar to ultrapure water with a purity of 1 and a purity of ≤0.1 μS / cm at 25°C according to DIN ISO 3696), i.e., the same volume as used in the alkali treatment.

[0393] - Seal the container with a sealing seal;

[0394] - Insert the container into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0395] - Treat the container at 121°C and 1 bar above ambient pressure for 6 hours;

[0396] - Open the sealing component;

[0397] - Empty the container;

[0398] - Fill and rinse the container twice with deionized water;

[0399] - Preferably, an air-dried container is used;

[0400] - Fill the drug container with 0.9 × (overflow volume) of n-hexane, which is the same volume used in the alkali treatment;

[0401] - Shake the drug container in a fixed-track shaker (80 rpm) for 30 minutes at room temperature;

[0402] - For example, using a Waters I-Class UPLC system with Waters Xevo qTOF, the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a hexane solution is analyzed by LC-MS to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0403] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0404] A*B / C,

[0405] Where A is the above-mentioned leaching value [mg / l] of one or more types of ions and / or compounds.

[0406] Where B is 0.9 × overflow volume, and

[0407] Where C is the wetted inner surface area of ​​the container (cm) 2 ); to obtain leaching values ​​[mg / cm³] of one or more types of ions and / or compounds, preferably Na ions or antioxidants. 2 ], which is the value of i.

[0408] The o value can be obtained by several methods, and preferably, the o value is determined as described herein. The o value is the content (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 ) and / or preferably by the methods described herein L o More preferably, the o value can be obtained through the method described herein. o Available.

[0409] If the same uncoated container used to obtain the value of i can be used, then the above method L iAn o value can be obtained using an uncoated container to determine the content (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 If the values ​​of i and o should be obtained through only one container, then the value of i is obtained through the method described above. i The value of o can be obtained through the following method L o Available. Preferably, o is obtained through method L. o Available. Method L o It can be used for containers with or without external coating; however, preferably, the exterior of the container is uncoated. Preferably, in method L... i and L o In the middle, the largest opening faces upwards.

[0410] Method L o

[0411] In this paper, method L o Includes the following steps:

[0412] - Provide a container, preferably for use in the above method L i Same container;

[0413] - If the container has two openings, such as a syringe: cover the smaller opening with a closure, such as a cap;

[0414] - Fill the drug container with 0.9 × (overflow volume) of solution;

[0415] - Seal the container with a sealing seal;

[0416] - Insert the container into the beaker, such as a stainless steel or aluminum beaker;

[0417] - Use 0.005 mol / L KOH solution (KOH: potassium hydroxide hydrate ≥ 99.995%) (Merck), fill the beaker with softened water (similar to ultrapure water of purity 1 with a purity of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) until the same level as the liquid in the container is reached;

[0418] - Seal the beaker with a sealing device;

[0419] - Insert the beaker into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0420] - Treat the beaker at 121°C and 1 bar above ambient pressure, for example, 2 bar, for 3 hours;

[0421] - Open the sealing part of the beaker;

[0422] - Empty the beaker;

[0423] - Fill and rinse the beaker twice with deionized water, and clean the exterior of the container by rinsing the outer surface with deionized water;

[0424] - Insert the container back into the beaker, such as a stainless steel or aluminum beaker;

[0425] - If the container is a glass container: use a 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) Dilute with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and fill the beaker until it reaches the same level as the liquid in the container, i.e., the same volume as used in the alkali treatment, or

[0426] - If the container is a polymer container: use a 0.1 mol / L HCl solution (30% hydrochloric acid). (Merck) Fill the beaker with softened water (similar to ultrapure water with a purity of 1 of ≤0.1 μS / cm at 25°C according to DIN ISO 3696) and isopropanol (1:1 / vol%:vol%) until the liquid level is the same as that in the container, i.e. the same volume used in the alkali treatment.

[0427] - Seal the beaker with a sealing device;

[0428] - Insert the beaker into an autoclave (e.g., Systec, model DX-150 (PM-CA-0001-01));

[0429] - Treat the beaker at 121°C and 1 bar above ambient pressure for 6 hours;

[0430] - Open the beaker;

[0431] - If the container is a glass container: for example, use a Varian SpectrAA 280FS (PE 3-004) to analyze the content (mg / l) of one or more types of ions and / or compounds, preferably Na ions, in a 0.1 mol / l HCl solution by FAAS analysis to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably Na ions;

[0432] - If the container is a polymer container: for example, use a Waters I-Class UPLC system with Waters Xevo qTOF to analyze by LC-MS the content (mg / l) of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants, in a 0.1 mol / l HCl solution to obtain the leaching value [mg / l] of one or more types of ions and / or compounds, preferably antioxidants and / or organic compounds, more preferably antioxidants;

[0433] - Calculate the value (mg / cm³) using the following formula. 2 ):

[0434] A*B / C,

[0435] Where A is the above value [mg / l] used for leaching one or more types of ions and / or compounds.

[0436] Where B is the volume of the solution in the beaker, and

[0437] Where C is the wetted outer surface of the container (cm) 2 ); to obtain leaching values ​​[mg / cm³] for one or more types of ions and / or compounds. 2 ], which is the o value.

[0438] Heat treatment

[0439] In a preferred embodiment, heat treatment can be performed prior to alkali treatment. Therefore, the pharmaceutical glass containers are tempered at 330°C for 60 minutes under ambient pressure in a preheating chamber. For alkali treatment, either heat-treated or untreated pharmaceutical glass containers can be used. Unless otherwise specified, the pharmaceutical glass containers are untreated pharmaceutical glass containers.

[0440] LC-MS

[0441] If polymer containers are used, LC-MS is used to determine the content of non-volatile organic compounds (NVOCs) in the solution. A Waters I-Class UPLC system with Waters Xevo qTOF (APCI) and a Waters Ascquity UPLC BEH column (100 × 2.1 mm, 1.7 μm) with a C18 pre-column (USP code L1) is used. The following experimental parameters are 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), reaching 20 / 80 within 1.0 min, 16 / 84 within 10.5 min, 6 / 94 within 1.0 min, 5.0 min / 7.0 min. 0 / 100 within clock (hold), 70 / 30 within 0.5 minutes / 5.5 minutes (hold); APCI probe temperature: 450℃; source temperature: 120℃; injection cone gas flow rate: 150L / h; desolvation gas flow rate: 1000L / h; corona voltage: 3.0kV; scan m / z: 100 to 2000 amu (positive and negative); ion source: APCI (atmospheric pressure chemical ionization); mode: MS E High CE: 20.00 to 45.00 eV; Low CE: 4.00 eV. The detection threshold estimated by the LC-MS method is 0.05 mg / L.

[0442] FAAS (Fuse Atomic Absorption Spectrometry)

[0443] If examining glass containers, FAAS is used to determine the concentration of inorganic ions in the solution. The detection threshold for the FAAS method is estimated to be 0.01 mg / L.

[0444] plan

[0445] In summary, the embodiments and preferred embodiments are as follows. The scope of protection is defined by the claims. Combinations of two or more, such as 3, 4, or 8 embodiments, are further preferred. The definitions and general statements herein preferably also apply to the following embodiments and preferred embodiments.

[0446] 1. A method for quality assessment of a coated container, comprising the following steps, preferably in this order:

[0447] - Provide coated containers;

[0448] - At least a portion of the coated surface of the coated container is treated with alkali to obtain an alkali-treated surface;

[0449] - Acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a post-treatment acid solution; and

[0450] - Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

[0451] 2. Preferably, the method for quality assessment of a coated container according to Scheme 1 includes the following steps, preferably in this order:

[0452] - Provide coated containers;

[0453] - Heat treatment is performed on at least a portion of the coated container to obtain a heat-treated surface;

[0454] - Perform alkali treatment on at least a portion of the heat-treated surface to obtain an alkali-treated surface;

[0455] - Acid treatment is performed on at least a portion of the alkali-treated surface to obtain an acid-treated surface and a post-treatment acid solution; and

[0456] - Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

[0457] 3. According to the method of any of the aforementioned schemes,

[0458] The alkali treatment includes, preferably, the following steps in this order, and preferably consists of:

[0459] - An alkaline solution with a pH >7 to 14, preferably 9 to 13, more preferably 9.5 to 12.5, and even more preferably 11.7, is brought into contact with at least a portion of the surface of the coated container, preferably a heat-treated surface; and

[0460] - Preferably, the alkaline-treated surface is filled and rinsed with ultrapure water at least part of it, preferably two or more times, more preferably three times.

[0461] 4. According to the method of any of the aforementioned schemes,

[0462] One or more of the following conditions must be met:

[0463] i) The contact time between the alkaline solution and at least a portion of the coated and / or 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

[0464] ii) Set the external pressure of the container to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably 1 bar higher than the ambient pressure; and / or

[0465] iii) Setting the external temperature of the container to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, and even more preferably 121°C; and / or

[0466] iv) wherein the container is filled with 10% to 100%, preferably 30% to 95%, more preferably 90% of its volume relative to its overflow volume [vol. / vol.]; and / or

[0467] v) The solution comprises water, preferably ultrapure water and an alkali, preferably an alkali, more preferably XOH (wherein X is selected from Na, K, Li), more preferably KOH, and preferably consists thereof; and / or

[0468] 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, and even more preferably 0.005 mol / L; and / or

[0469] vii) wherein the container is preferably sealed by a closed seal during alkali treatment.

[0470] 5. According to the method of any of the foregoing schemes,

[0471] The heat treatment includes the following steps, preferably consisting of:

[0472] - Temper the container.

[0473] 6. According to the method of any of the foregoing schemes,

[0474] One or more of the following conditions must be met:

[0475] i) The tempering time is from 1 minute to 1 day, preferably from 30 minutes to 6 hours, more preferably 60 minutes; and / or

[0476] ii) Setting the temperature outside the container during tempering to 25°C to the Tg of the container substrate, preferably 50°C to 500°C, more preferably 100°C to 400°C, more preferably 300°C to 400°C, and more preferably 330°C; and / or

[0477] iii) Set the pressure during tempering to 0.1 bar to 10 bar, preferably ambient pressure.

[0478] 7. According to the method of any of the foregoing schemes,

[0479] The acid treatment includes the following steps, preferably consisting of the following:

[0480] - An acid solution with a pH of <7, preferably 0 to 6, preferably 0 to 3, more preferably 0 to 2, more preferably 1 is brought into contact with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution.

[0481] 8. According to the method of any of the foregoing schemes,

[0482] The acid treatment includes the following steps, preferably consisting of the following:

[0483] -Contact the acid solution with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution:

[0484] One or more of the following conditions must be met:

[0485] i) The contact time between the acid solution and at least a portion of the alkali-treated surface is from 1 second to 1 week, preferably from 1 minute to 1 day, more preferably from 1 hour to 10 hours, and even more preferably 6 hours; and / or

[0486] ii) Set the external pressure of the container to 0.1 bar to 10 bar, preferably 0.5 bar to 4 bar, more preferably 1 bar higher than the ambient pressure; and / or

[0487] iii) Setting the external temperature of the container to 20°C to 200°C, preferably 50°C to 200°C, more preferably 100°C to 150°C, and even more preferably 121°C; and / or

[0488] iv) Wherein the container is filled with the solution to the filling volume according to ISO 4802-2:2016(E), section 7.2; and / or

[0489] v) Wherein, relative to the overflow volume of the container [vol. / vol.], the container is filled with solution up to 10% to 100%, preferably 30% to 95%, more preferably 90% of its volume; and / or

[0490] vi) The solution comprises water, preferably ultrapure water and an acid, preferably an acid, more preferably HX (wherein X is selected from F, Cl, Br and / or I), more preferably HCl, preferably composed of the above, and / or

[0491] 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, and even more preferably 0.1 mol / L; and / or

[0492] viii) wherein the solution comprises an organic solvent, preferably an alcohol, an ester and / or an ether, more preferably an alcohol, more preferably an isopropanol; and / or;

[0493] ix) wherein the ratio of water to organic solvent [vol. / vol.] is 0.1 to 10, preferably 0.3 to 0.7, more preferably 0.4 to 0.6, and even more preferably 0.5; and / or

[0494] x) Wherein the container is preferably sealed by a closed seal during acid treatment.

[0495] 9. According to the method of any of the foregoing schemes,

[0496] The quality assessment result is obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively determining the content of one or more types of ions and / or compounds in the acid solution after treatment.

[0497] 10. The method according to any of the foregoing schemes,

[0498] The quality assessment result is obtained by leaching at least a portion of the acid-treated surface with one or more types of ions and / or compounds to obtain a quantitative quality assessment result. The quality assessment result is obtained by leaching at least a portion of the acid-treated surface with one or more types of ions, preferably alkali metal ions, more preferably Na ions.

[0499] 11. The method according to any of the foregoing schemes,

[0500] The quality assessment results are obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively determining the content of the following substances in the acid solution after treatment:

[0501] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0502] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0503] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0504] 12. According to the method of any of the foregoing schemes,

[0505] Quantification is performed 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

[0506] Quantification was performed 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

[0507] Quantification was achieved using titration.

[0508] 13. Preferably, the method according to any of the foregoing schemes includes the following steps:

[0509] - The suitability of the coated container for the storage solution, preferably the drug solution, is evaluated using quality assessment results obtainable according to any of the foregoing methods; and / or

[0510] - The stability of the coating on the coated container, preferably the coated drug container, is evaluated using quality assessment results obtainable according to any of the foregoing methods; and / or

[0511] - The quality assessment results obtainable by means of any of the foregoing schemes shall be linked and / or associated with the coated container, preferably the coated drug container.

[0512] 14. Preferably, the method according to any of the foregoing schemes includes the following steps, preferably in this order:

[0513] - The first and second coated containers are produced using the same production method;

[0514] -By the method according to any of the foregoing schemes, preferably the method described herein L i Quantitative leaching of the first coated container is used to obtain a quality assessment result for the first coated container; and

[0515] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, and / or use the quality assessment results for the quality control of the first and / or second containers; and / or

[0516] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, wherein the first coated container exhibits, relative to the hydrolysis limit of Class 1 glass containers, one or more types of ions and / or compounds, more preferably, a leaching rate of Na ions <90%, preferably <50%, more preferably <30%; and / or

[0517] - The suitability of the second-coated container for the solution preferably stored in the second container is determined by applying and / or using the quality assessment results of the first-coated container, wherein the first-coated container exhibits, relative to the maximum limit in the hydrolysis resistance container surface test of ISO 4802-2:2016(E), Section 9.2, for HCF1 and HCF2 classes, the leaching of one or more types of ions and / or compounds, preferably <90%, preferably <50%, more preferably <30% of Na ions; and / or

[0518] - Apply and / or use the quality assessment results of the first coated container to determine the suitability of the second coated container for the solution preferably stored in the second container, wherein the first coated container exhibits leaching of one or more types of ions and / or compounds at a concentration of less than 10.00 mg / L, preferably less than 5.00 mg / L, more preferably less than 4.5 mg / L, more preferably less than 4.1 mg / L, more preferably less than 3.2 mg / L, more preferably less than 2.5 mg / L, more preferably less than 2.0 mg / L, more preferably less than 1.5 mg / L, more preferably less than 1.2 mg / L, more preferably less than 1.0 mg / L, more preferably less than 0.75 mg / L, more preferably less than 0.50 mg / L, more preferably less than 0.40 mg / L, more preferably less than 0.30 mg / L, more preferably less than 0.2 mg / L, more preferably less than 0.1 mg / L.

[0519] 15. The method according to any of the foregoing schemes includes the following steps:

[0520] - The first coated container is filled with a solution, preferably a pharmaceutical composition, more preferably a pharmaceutical solution with a pH of 4 to 14, preferably >7 to 12, more preferably 9 to 11.

[0521] 16. Use of the quality assessment results obtainable by means of any of the schemes 1 to 12 for evaluating the suitability of the coated container, preferably the coated pharmaceutical container, for the storage solution, preferably the pharmaceutical solution, and / or for quality control of the production of the coated container.

[0522] 17. A coated container,

[0523] Leaching of one or more types of ions and / or compounds is obtained by a method according to any of the foregoing schemes, preferably by the method described herein. i Available, and

[0524] The leaching of one or more types of ions and / or compounds is below 5.00 mg / L.

[0525] 18. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0526] Leaching of one or more types of ions and / or compounds is obtained by a method according to any of the foregoing schemes, preferably by the method described herein. i Available, and

[0527] The leaching of one or more types of ions and / or compounds is less than 10.00 mg / L, preferably less than 5.00 mg / L, more preferably less than 4.5 mg / L, more preferably less than 4.1 mg / L, more preferably less than 3.2 mg / L, more preferably less than 2.5 mg / L, more preferably less than 2.0 mg / L, more preferably less than 1.5 mg / L, more preferably less than 1.2 mg / L, more preferably less than 1.0 mg / L, more preferably less than 0.75 mg / L, more preferably less than 0.50 mg / L, more preferably less than 0.40 mg / L, more preferably less than 0.30 mg / L, more preferably less than 0.2 mg / L, and more preferably less than 0.1 mg / L.

[0528] 19. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0529] The maximum limit relative to the surface test of hydrolysis resistant containers in ISO 4802-2:2016(E), Section 9.2, for HCF1 and HCF2 classes, obtained by the method according to any of the foregoing schemes, preferably by the method described herein. i The leaching of one or more types of ions and / or compounds is less than 100%, preferably less than 90%, more preferably less than 50%, more preferably less than 50%, and more preferably more than 1% to less than 30%.

[0530] 20. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0531] Wherein, L is obtained by any of the foregoing schemes, preferably by the method described herein. i The leaching of one or more types of ions and / or compounds that are available is called a;

[0532] Where a ≤ b*c;

[0533] If 0.9 × the container's (overflow volume) ≤ 1 ml, then b is 5.00 mg / l.

[0534] If 0.9 × the container's (overflow volume) > 1 ml and ≤ 2 ml, then b is 4.50 mg / L.

[0535] If 0.9 × the container's (overflow volume) > 2 ml and ≤ 3 ml, then b is 4.10 mg / L.

[0536] If 0.9 × the container's (overflow volume) > 3 ml and ≤ 5 ml, then b is 3.20 mg / L.

[0537] If 0.9 × the container's (overflow volume) > 5 ml and ≤ 10 ml, then b is 2.50 mg / L.

[0538] If 0.9 × the container's (overflow volume) > 10 ml and ≤ 20 ml, then b is 2.00 mg / L.

[0539] If 0.9 × the container's (overflow volume) > 20 ml and ≤ 50 ml, then b is 1.50 mg / L.

[0540] If 0.9 × container's (overflow volume) > 50 ml and ≤ 100 ml, then b is 1.20 mg / L.

[0541] If 0.9 × the container's (overflow volume) > 100 ml and ≤ 200 ml, then b is 1.00 mg / L.

[0542] If 0.9 × container (full capacity) > 200 ml and ≤ 500 ml, then b is 0.75 mg / L; and

[0543] If 0.9 × the container's (overflow volume) > 500 ml, then b is 0.50 mg / L; and

[0544] Wherein 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.

[0545] 21. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0546] Wherein, L is obtained by any of the foregoing schemes, preferably by the method described herein. iThe leaching of one or more types of ions and / or compounds that are available is a;

[0547] Wherein 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.

[0548] 22. Preferably, the method, application, and / or coating container according to any of the foregoing embodiments,

[0549] The coated container includes an inner surface and an outer surface, wherein at least a portion of the inner surface is coated with a coating; and

[0550] The coated container exhibits the following equation:

[0551] i / o≤d

[0552] d value ([mg / cm) 2 ] / [mg / cm 2 The value is 0.90.

[0553] Where i is obtained by a method according to any of the foregoing schemes, preferably by the method L described herein. i Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 );and

[0554] Where o is the leaching (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 ) and / or through the methods described herein L o Available.

[0555] 23. Preferably, the method, application, and / or coating container according to any of the foregoing embodiments,

[0556] 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.

[0557] 24. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0558] The coated container exhibits the following equation:

[0559] i / o≥e

[0560] The e-value ([mg / cm2] / [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.

[0561] Where i is obtained by a method according to any of the foregoing schemes, preferably by the method L described herein. i Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 );and

[0562] Where o is the leaching (mg / cm³) of one or more types of ions and / or compounds in the substrate of the coated container. 2 ) and / or through the methods described herein L o Available.

[0563] 25. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0564] Where i is 1.0 * 10 -10 mg / cm 2 Up to 1.0*10 -3 mg / cm 2 Preferably 1.0*10 -8 mg / cm 2 Up to 6.5*10 -4 mg / cm 2 More preferably 1.0*10 -7 mg / cm 2 Up to 6.0*10 -4 mg / cm 2 More preferably 1.0*10 -6 mg / cm 2 Up to 3.0*10 -4 mg / cm 2 More preferably 7.0*10 -6 mg / cm 2 Up to 3.0*10 -5 mg / cm 2 .

[0565] 26. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0566] Where o is 1.1 * 10 -5 mg / cm 2 Up to 1.0*10 -1 mg / cm 2 Preferably 1.0*10 -4 mg / cm 2 Up to 1.0*10-2 mg / cm 2 More preferably 6.5*10 -4 mg / cm 2 Up to 1.0*10 -3 mg / cm 2 More preferably 6.8*10 -4 mg / cm 2 Up to 7.5*10 -4 mg / cm 2 .

[0567] 27. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0568] Where i is obtained through the method described in this article L i Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 );and

[0569] Where o is obtained through the method described in this article L o Leaching of one or more types of ions and / or compounds available (mg / cm³) 2 ).

[0570] 28. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0571] Where o represents the leaching of one or more types of ions and / or compounds from an uncoated container (mg / cm³). 2 The uncoated container can be obtained by the same production method as the coated container, wherein o can be obtained by the method according to any of the foregoing schemes and / or by the method described herein. i Available.

[0572] 29. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0573] One or more types of 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.

[0574] 30. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0575] One or more types of ions and / or compounds are:

[0576] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0577] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0578] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0579] 31. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0580] The coating can be obtained by a coating method, preferably a CVD method, more preferably a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma pulsed chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably a plasma pulsed chemical vapor deposition (PICVD) method.

[0581] 32. Preferably, the method, application, and / or coating container according to any of the foregoing embodiments,

[0582] The coating is a coating that can be obtained by a pretreatment and coating method, preferably a CVD method, more preferably a plasma-enhanced chemical vapor deposition (PECVD) method, a plasma pulsed chemical vapor deposition (PICVD) method, or a plasma-assisted chemical vapor deposition (PACVD) method, preferably a plasma pulsed chemical vapor deposition (PICVD) method, wherein the pretreatment is performed before the coating method.

[0583] 33. Preferably, the method, application, and / or coating container according to any of the foregoing embodiments,

[0584] The coating method includes the following steps:

[0585] - Provide a container, preferably a glass container, including a surface;

[0586] - A coating process is performed on at least a portion, preferably the inner surface, of the container, comprising the steps of:

[0587] a) Enclosing at least a portion, preferably the inner surface, of the container through the precursor P1; and

[0588] b) Irradiate precursor P1 to generate plasma;

[0589] Wherein at least one, preferably all, of the following parameters are satisfied:

[0590] i) wherein the process temperature PT1 is 200°C to the Tg of the glass element, preferably 200°C to 500°C, more preferably 220°C to 450°C, more preferably 240°C to 320°C, and more preferably 250°C to 300°C; and / or

[0591] ii) wherein the plasma pulse duration PD1 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 or less; and / or

[0592] iii) wherein the plasma pulse duration PD1 is 0.1 μs or more, preferably 0.5 μs or more, more preferably 1 μs or more, and even more preferably 6 μs or more; and / or

[0593] iv) wherein the irradiation is performed by a microwave generator, preferably wherein the radiation has 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, and more preferably 2.45 GHz; and / or

[0594] v) wherein the input power IP1, preferably the microwave generator's input power IP1 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

[0595] vi) wherein the precursor P1 comprises one or more of hexamethyldisiloxane (HMDSO), hexamethyldisilazane (HMDS), tetramethylsilane (TMS), trimethylborazole (TMB), tris(dimethylaminosilyl)-amino-di(dimethylamino)borane (TDADB), tris(trimethylsilane)borate (TMSB), hexamethylcyclotrisiloxane (HMCTSO), octamethylcyclotetrasiloxane (OMCTS), decamethylcyclopentasiloxane (DMCPS), dodecylcyclohexasiloxane (DMCHS), diacetoxy-di-tert-butoxysilane (DADBS), tetraethoxysilane (TEOS), tris(trimethylsiloxy)vinylsilane (TTMSVS), and vinyltriethoxysilane (VTES) and / or combinations thereof, preferably the precursor P1 is HMDSO; and / or

[0596] vii) wherein the precursor P1 comprises elements Si, C, O, and H, preferably composed of them; and / or

[0597] 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

[0598] 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

[0599] x) The ratio of all pulse durations PD1 [μs] to all pulse pause times PP1 [ms] [μs / ms] is 1 or more, preferably 2 or more, more preferably 2 to 50, more preferably 3 to 8; and / or

[0600] xi) wherein 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, and more preferably 0.8 mbar; and / or

[0601] xii) wherein the process temperature decreases, preferably decreases steadily, during the coating process; and / or

[0602] xiii) wherein the process temperature PT1 is at least partially, preferably at least 220°C, preferably at least 240°C, more preferably at least 250°C, more preferably at least 255°C, more preferably at least 270°C, and more preferably at least 280°C; and / or

[0603] xiv) wherein the flow rate of precursor P1 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 30 sccm, and even more preferably 10 to 15 sccm.

[0604] 34. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0605] The pretreatment includes the following plasma pretreatment steps:

[0606] - Provide a container, preferably a glass container, including a surface;

[0607] - A coating process is performed on at least a portion, preferably the inner surface, of the container, comprising the following steps:

[0608] a) The precursor P2 surrounds at least a portion, preferably the inner surface, of the container; and

[0609] b) Irradiate precursor P2 to generate plasma;

[0610] Wherein at least one, preferably all, of the following parameters are satisfied:

[0611] i) wherein the process temperature PT2 is from room temperature to the Tg of the glass element, preferably from room temperature to 450°C, more preferably from room temperature to 400°C, more preferably from room temperature to 320°C, and even more preferably from room temperature to 280°C; and / or

[0612] ii) wherein the plasma pulse duration PD2 is less than 50 ms, preferably less than 40 ms, preferably less than 30 ms, more preferably less than 20 ms, more preferably less than 15 ms, more preferably less than 8 ms, more preferably less than 6 ms, more preferably less than 1 ms, and more preferably less than 0.5 ms; and / or

[0613] iii) wherein the plasma pulse duration PD2 is 0.1 ms or more, preferably 0.2 ms or more, more preferably 0.3 ms or more, and even more preferably 0.5 ms or more; and / or

[0614] iv) wherein the irradiation is performed by a microwave generator, preferably wherein the radiation has 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, and more preferably 2.45 GHz; and / or

[0615] v) wherein the input power IP2, preferably the microwave generator's input power IP2 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

[0616] vi) Precursor P2 includes argon, oxygen and / or nitrogen, preferably oxygen, more preferably air; and / or

[0617] vii) wherein the precursor P2 comprises element N (e.g., N2) and / or O (e.g., element O2), preferably N2 and O2, more preferably O2, and preferably composed thereof; and / or

[0618] 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

[0619] 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

[0620] x) The ratio of all pulse durations PD2 [ms] to all pulse pause times PP2 [ms] [ms / ms] is 0.05 or more, preferably 0.1 or more, more preferably 0.15 to 5, more preferably 0.2 to 0.5; and / or

[0621] xi) wherein 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

[0622] xii) wherein the process temperature PT2 increases, preferably steadily, during plasma pretreatment; and / or

[0623] xiii) wherein the process temperature PT2 is at least partially, preferably at least 220°C, preferably at least 240°C, more preferably at least 250°C, more preferably at least 255°C, more preferably at least 270°C, and more preferably at least 280°C at the end of the plasma pretreatment process; and / or

[0624] xiv) wherein the flow rate of precursor P2 is 0.1 to 500 sccm, preferably 5 to 100 sccm, more preferably 8 to 50 sccm, and even more preferably 20 to 30 sccm.

[0625] 35. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0626] The inner surface of the container, preferably the entire inner surface of the container, is coated.

[0627] 36. Preferably, the method, use, and / or coated container according to any of the foregoing embodiments,

[0628] The outer surface of the container was not coated.

[0629] 37. Preferably, the method, application, and / or coating container according to any of the foregoing embodiments,

[0630] The substrate of the coated container includes glass, preferably borosilicate glass or aluminoborosilicate glass, more preferably borosilicate glass, and is preferably composed of the like.

[0631] 38. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0632] The glass comprises, preferably, the following components in weight percent:

[0633] SiO2: 30-98%, preferably 50-90%, more preferably 70.0-74.0%;

[0634] B2O3: 0-30%, preferably 3-20%, more preferably 7.0-16.0%;

[0635] Al2O3: 0-30%, preferably 1-15%, more preferably 3.0-6.5%;

[0636] X2O: 0-30%, preferably 1-15%, more preferably 2.0-7.2%, wherein X is selected from Na, K, Li, preferably Na and / or K, more preferably Na;

[0637] YO: 0-30%, preferably 0.1-5%, more preferably 0.5-1.0%, wherein Y is selected from Ca, Mg, Ba, and preferably Y is Ca and / or Mg; and

[0638] Preferably, unavoidable impurities.

[0639] 39. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0640] The substrate of the coated container includes a polymer, preferably a cyclic olefin copolymer (COC) and / or a cyclic olefin polymer (COP), more preferably a cyclic olefin copolymer (COC), and is preferably composed of the like.

[0641] 40. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0642] The substrate of the coated container includes:

[0643] - One or more compounds containing C, preferably one or more compounds containing C but excluding compounds containing Si; and / or

[0644] - one or more monomers, preferably norbornene, norbornane and / or bicyclopentane; and / or

[0645] - One or more antioxidants, preferably wherein the antioxidant is selected from the group consisting of: phenolic antioxidants, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); phosphite antioxidants, more preferably tris(2,4-di-tert-butylphenyl) phosphite; phosphonite antioxidants, preferably tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-diyldiphosphonite; thioether antioxidants; more preferably, wherein the antioxidant is a phenolic antioxidant, more preferably pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

[0646] 41. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0647] The overflow volume 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.

[0648] 42. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0649] The coated container is a coated drug container, preferably a coated vial, a coated syringe, a coated ampoule or a coated cartridge, more preferably a coated vial.

[0650] 43. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0651] The coated container is a coated drug container, preferably a cartridge or syringe, more preferably a syringe, wherein the smaller opening of the cartridge or syringe, preferably the syringe, is preferably closed by a top cap and / or a stopper.

[0652] 44. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0653] 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

[0654] At least a portion of the coated surface includes at least a portion of the inner surface, preferably at least a portion of the coated surface is the surface that is in contact with the solution when the coated container is standing upright on a flat surface and is filled with 10% or more, preferably 30% or more, more preferably 90% or more, more preferably 90% of the volume of the solution relative to the overflow volume [vol. / vol.] of the coated container; and / or

[0655] At least a portion of the coated surface is the surface that comes into contact with the solution when the coated container is filled to the filling volume according to ISO 4802-2:2016(E), section 7.2.

[0656] 45. Preferably, the method, use, and / or coating container according to any of the foregoing embodiments,

[0657] The substrate of the container contains one or more types of ions and / or compounds.

[0658] 46. ​​A kit comprising:

[0659] i) Preferably, the container coated according to any of the foregoing schemes, and

[0660] ii) A data table or storage medium that includes quality assessment results obtainable by means of any of the foregoing schemes. Attached Figure Description

[0661] There are several ways to advantageously design and further develop the teachings of the invention. To this end, reference is made, on the one hand, to the patent claims which are dependent on the independent patent claims, and on the other hand, to the following description of preferred examples of embodiments of the invention illustrated by means of the accompanying drawings. Further developments of generally preferred embodiments and teachings will be described in conjunction with the description of preferred embodiments of the invention with the aid of the accompanying drawings.

[0662] Figure 1 It is a schematic view of a surface that is at least partially coated;

[0663] Figure 2 It is a schematic view of a surface that is at least partially pretreated and at least partially coated;

[0664] Figure 3 These are schematic views of embodiments of the present invention;

[0665] Figure 4 This is a block diagram of a method according to an embodiment of the present invention.

[0666] In the following description of the embodiments, the same reference numerals denote similar parts. Detailed Implementation

[0667] Figure 1 and 2Schematic views illustrating embodiments of the present invention are depicted. Figure 1 In the diagram, glass surface 1 is partially coated with coating 2. The coating depicted is a single layer. Therefore, the coating is in direct contact with glass surface 1 and is the outermost layer. Figure 2 In this process, the partially pretreated glass surface 3 is partially coated with coating 2. The coating depicted is a single layer. Therefore, the coating is in direct contact with the glass surface 1 and is the outermost layer. Figure 3 A schematic view of an embodiment of the invention is shown. The outer surface 4 of the container is uncoated, while the inner surface 5 of the container is coated. The upper surface of the container crown is neither part of the outer surface 4 nor the inner surface 5 of the container and is preferably uncoated.

[0668] Figure 4 A block diagram of a method according to an embodiment of the present invention is shown. First, in 1001, a coated container is provided, which may be heat-treated or untreated. Then, in 1002, at least a portion of the coated surface of the coated container is subjected to alkali treatment to obtain an alkali-treated surface. Next, in 1003, at least a portion of the alkali-treated surface is subjected to acid treatment to obtain an acid-treated surface and a treated acid solution. Finally, in 1004, the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface is quantified to obtain a quality assessment result.

[0669] The invention is further illustrated by the following examples.

[0670] Example 1

[0671] Unless otherwise specified, Example 1 is prepared according to EP 0 821 079 A1, EP 0 811 367 A2, WO 03 015122 A1 and EP 2 106 461 A1.

[0672] Two 10R vials (SCHOTT AG EVERIC) are provided. TM (pure). As a first pretreatment, a washing pretreatment was performed in which the vials were washed in a laboratory dishwasher (HAMO AG LS-2000) with ultrapure water at 25°C for 2 minutes at room temperature, 6 minutes at 40°C, and then washed at room temperature for 25 minutes. Afterward, the vials were dried at 300°C for 20 minutes.

[0673] Subsequently, the two vials were simultaneously processed and coated using equipment according to WO 03 015 122 A1. Microwave radiation at a frequency of 2.45 GHz was used for all plasma treatments. The reaction chamber was the interior of the vials. The exterior of the vials was the ambient environment.

[0674] First, the vials were evacuated until a pressure of 0.05 mbar was reached. Then, oxygen was filled into the vials (50 sccm for both vials) until a pressure of 5 mbar was reached, and plasma pretreatment began. The plasma was excited at an input power of 6700 W (for both vials) in pulsed mode, with a pulse duration of 0.5 ms and a pulse pause of 1.8 ms. Plasma pretreatment lasted for 14 seconds until the vial temperature reached 280 °C, measured using a pyrometer at the midpoint of the cylindrical section of the vial.

[0675] The coating process followed immediately. The vials were filled with HMDSO (flow rate: 25 sccm for two vials) and the pressure was set to 0.8 mbar. The vials were then irradiated for 0.2 seconds (pressure: 0.8 mbar, flow rate: 25 sccm HMDSO for two vials, 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: 25 sccm HMDSO for two vials, input power: 3250 W, pulse duration: 0.003 ms, pulse pause time: 1 ms).

[0676] Next, post-processing is performed, which involves filling the vials with argon gas and cooling them to room temperature in the presence of argon gas to obtain two vials with the same coating.

[0677] Example 2

[0678] Unless otherwise specified, Example 2 is prepared according to EP 0 821 079 A1, EP 0 811 367 A2, WO 03 015122 A1 and EP 2 106 461 A1.

[0679] Two 10R vials (SCHOTT AG EVERIC) are provided. TM (pure). As a first pretreatment, a washing pretreatment was performed in which the vials were washed in a laboratory dishwasher (HAMO AG LS-2000) with ultrapure water at 25°C for 2 minutes at room temperature, 6 minutes at 40°C, and then washed at room temperature for 25 minutes. Afterward, the vials were dried at 300°C for 20 minutes.

[0680] Subsequently, the two vials were simultaneously processed and coated using equipment according to WO 03 015 122 A1. Microwave radiation at a frequency of 2.45 GHz was used for all plasma treatments. The reaction chamber was the interior of the vials. The exterior of the vials was the ambient environment.

[0681] First, the vials were evacuated until a pressure of 0.05 mbar was reached. Then, oxygen was filled into the vials (50 sccm for both vials) until a pressure of 1.2 mbar was reached, and plasma pretreatment began. The plasma was excited with an input power of 5500 W in pulsed mode, with a pulse duration of 0.5 ms and a pulse pause time of 1.8 ms. Plasma pretreatment lasted for 27 seconds until the vial temperature reached 280°C, measured using a pyrometer at the center of the cylindrical section of the vial.

[0682] The coating process followed immediately (11 seconds). The vials were filled with HMDSO (flow rate: 25 sccm for both vials) and the pressure was set to 0.8 mbar. The vials were then irradiated for 0.2 seconds (pressure: 0.8 mbar, flow rate: 25 sccm HMDSO for both vials, input power: 6000 W, pulse duration: 0.050 ms, pulse pause time: 30 ms), followed by 11 seconds (pressure: 0.8 mbar, flow rate: 25 sccm HMDSO for both vials, input power: 4500 W, pulse duration: 0.008 ms, pulse pause time: 0.5 ms). After the coating process, the vial temperature was 280°C, measured using a pyrometer at the center of the cylindrical portion of the vial.

[0683] Next, post-processing is performed, which involves filling the vials with oxygen and cooling them to room temperature in the presence of oxygen to obtain two equally coated vials.

[0684] Examples 3 and 4

[0685] Example 3 is SCHOTT Top 10R vials, Example 4 is uncoated SCHOTT Everic TM Pure 10R small bottle.

[0686] Table 1 illustrates the method described in this paper. i The values ​​available are examples 1 through 4.

[0687] Table 1: Leaching values ​​of Examples 1 to 4

[0688]

[0689] *o Method L via uncoated containers i Measurement

[0690] List of reference numerals

[0691] 1. Glass surface

[0692] 2. Coating

[0693] 3. Pre-treated glass surface

[0694] 4. The outer surface of the container

[0695] 5. Inner surface of the container

[0696] 6. The upper surface of the container crown

[0697] 1001 Provides a coated container;

[0698] 1002 At least a portion of the coated surface of the coated container is subjected to alkali treatment to obtain an alkali-treated surface;

[0699] 1003 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;

[0700] 1004 Quantitatively measure the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

Claims

1. A method for quality assessment of a coated pharmaceutical container, comprising the following steps: - Provides coated drug containers, wherein the coating can be obtained by CVD methods; - At least a portion of the coated surface of the coated drug container is treated with alkali to obtain an alkali-treated surface; - 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; and - To obtain quality assessment results, quantify the leaching of at least a portion of the acid-treated surface with one or more types of ions and / or compounds. Among them, the following conditions must be met: i) The contact time between the alkaline solution and at least a portion of the coated surface and / or the heat-treated surface is from 1 second to 1 week, and / or the contact time between the acid solution and at least a portion of the alkaline-treated surface is from 1 second to 1 week; ii) Set the external pressure of the container to 0.1 bar to 10 bar; iii) Set the external temperature of the container to 20°C to 200°C; iv) Wherein the container is filled with the solution to the filling volume according to ISO 4802-2:2016(E), section 7.2; and / or v) Where, relative to the overflow volume of the container, the container is filled with solution until it reaches 10% to 100% of its volume; and The leaching of at least a portion of the acid-treated surface with one or more types of ions and / or compounds is used to obtain a quality assessment result that quantifies the content of the following substances: - One or more types of alkali metal ions; and / or - One or more compounds containing C; and / or - One or more monomers; and / or - One or more antioxidants, wherein the antioxidants are selected from the group consisting of: phenolic antioxidants; phosphite antioxidants; phosphonite antioxidants; thioether antioxidants.

2. The method according to claim 1, comprising the following steps: - Provide coated drug containers; - Heat treatment is performed on at least a portion of the coated drug container to obtain a heat-treated surface; - At least a portion of the heat-treated surface is subjected to alkali treatment to obtain an alkali-treated surface; - 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; and - Quantify the leaching of one or more types of ions and / or compounds from at least a portion of the acid-treated surface to obtain quality assessment results.

3. The method according to claim 1 or 2, The alkaline treatment includes or consists of the following steps: - To bring an alkaline solution with a pH > 7 to 14 into contact with at least a portion of the surface of the coated drug container; and - Fill and rinse at least part of the alkaline-treated surface with ultrapure water.

4. The method according to claim 3, wherein the pH of the alkaline solution is 9 to 13.

5. The method according to claim 3, wherein the pH of the alkaline solution is from 9.5 to 12.

5.

6. The method according to claim 3, wherein the pH of the alkaline solution is 11.

7.

7. The method of claim 3, wherein the alkaline solution is brought into contact with at least a portion of the heat-treated surface of the coated drug container.

8. The method of claim 3, wherein at least a portion of the alkali-treated surface is filled and rinsed with ultrapure water two, three, or more times.

9. The method according to claim 1 or 2, One or more of the following conditions must be met: i) The contact time between the alkaline solution and at least a portion of the coated and / or heat-treated surface is from 1 minute to 1 day; and / or ii) Set the external pressure of the container to 0.5 bar to 4 bar; and / or iii) Set the external temperature of the container to 50°C to 200°C; and / or iv) Wherein the container is filled with solution to 30% to 95% of its full volume relative to its overflow volume; and / or v) The solution contains water and alkali, or is composed of them; and / or vi) The concentration of the base is from 0.0001 mol / L to 1 mol / L; and / or vii) Where the container is closed during alkali treatment.

10. The method according to claim 9, in, i) The contact time between the alkaline solution and at least a portion of the coated and / or heat-treated surface is 1 to 5 hours; and / or ii) Set the external pressure of the container to ambient pressure + 1 bar; and / or iii) Set the external temperature of the container to 100°C to 150°C; and / or iv) Where the container is filled with solution at 90% of its full volume relative to its overflow volume; and / or v) The solution contains ultrapure water and a base, or is composed of the same; and / or vi) The concentration of the base is from 0.001 mol / L to 0.11 mol / L; and / or vii) Where the container is sealed by a closed seal during alkali treatment.

11. The method according to claim 9, in, i) The contact time between the alkaline solution and at least a portion of the coated and / or heat-treated surface is 3 hours; and / or ii) Set the external temperature of the container to 121°C; and / or v) The solution contains water and XOH, wherein X is selected from Na, K, Li, or is composed of them; and / or vi) The concentration of the base is from 0.003 mol / L to 0.020 mol / L.

12. The method according to claim 9, in, v) The solution contains water and KOH, or is composed of them; and / or vi) The concentration of the base is 0.005 mol / L.

13. The method according to claim 2, The heat treatment includes or consists of the following steps: The container is tempered, wherein one or more of the following conditions are met: i) Tempering time is from 1 minute to 1 day; and / or ii) Set the external temperature of the container during tempering to 25°C to the Tg of the container substrate; and / or iii) Set the pressure during tempering to 0.1 bar to 10 bar.

14. The method according to claim 13, in, i) Tempering time is 30 minutes to 6 hours; and / or ii) Set the external temperature of the container during tempering to 50°C to 500°C; and / or iii) Set the pressure during tempering to ambient pressure.

15. The method according to claim 13, in, i) The tempering time is 60 minutes; and / or ii) Set the temperature outside the container to 100°C to 400°C during tempering.

16. The method according to claim 13, in, ii) Set the temperature outside the container to 300°C to 400°C during tempering.

17. The method according to claim 13, in, ii) Set the temperature outside the container to 330°C during tempering.

18. The method according to claim 1 or 2, The acid treatment includes or consists of the following steps: - Contact an acidic solution with pH < 7 with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acidic solution.

19. The method of claim 18, wherein the pH of the acid solution is from 0 to 6.

20. The method of claim 18, wherein the pH of the acid solution is from 0 to 3.

21. The method of claim 18, wherein the pH of the acid solution is from 0 to 2.

22. The method of claim 18, wherein the pH of the acid solution is 1.

23. The method according to claim 1 or 2, The acid treatment includes or consists of the following steps: - Contact the acid solution with at least a portion of the alkali-treated surface to obtain an acid-treated surface and a treated acid solution: One or more of the following conditions must be met: i) The contact time of the acid solution with at least a portion of the alkali-treated surface is from 1 minute to 1 day; and / or ii) Set the external pressure of the container to 0.5 bar to 4 bar; and / or iii) Set the external temperature of the container to 50°C to 200°C; and / or v) Wherein, relative to the overflow volume of the container, the container is filled with solution until it reaches 30% to 95% of its volume; and / or vi) The solution contains water and acid, or is composed of them; and / or vii) The concentration of the acid is from 0.0001 mol / L to 1 mol / L; and / or viii) Where the solution contains an organic solvent; and / or ix) wherein the volume ratio of water to organic solvent is 0.1 to 10; and / or x) The container is closed during acid treatment.

24. The method according to claim 23, in, i) The contact time of the acid solution with at least a portion of the alkali-treated surface is 1 to 10 hours; and / or ii) Set the external pressure of the container to ambient pressure + 1 bar; and / or iii) Set the external temperature of the container to 100°C to 150°C; and / or v) Where the container is filled with solution until it reaches 90% of its full volume, relative to its overflow volume; and / or vi) The solution contains ultrapure water and an acid, or is composed of the same; and / or vii) The concentration of the acid is from 0.01 mol / L to 0.5 mol / L; and / or viii) Where the solution contains alcohols, esters and / or ethers; and / or ix) wherein the volume ratio of water to organic solvent is 0.3 to 0.7; and / or x) The container is sealed by a sealing element during acid treatment.

25. The method according to claim 23, in, i) The contact time of the acid solution with at least a portion of the alkali-treated surface is 6 hours; and / or iii) Set the external temperature of the container to 121°C; and / or vi) The solution contains water and HX, wherein X is selected from F, Cl, Br and / or I, or is composed of them; and / or vii) The concentration of the acid is from 0.05 mol / L to 0.2 mol / L; and / or viii) Where the solution contains alcohol; and / or ix) wherein the volume ratio of water to organic solvent is 0.4 to 0.

6.

26. The method according to claim 23, in, vi) The solution contains water and HCl, or is composed of them; and / or vii) The concentration of the acid is 0.1 mol / L; and / or viii) Wherein the solution contains isopropanol; and / or ix) where the volume ratio of water to organic solvent is 0.

5.

27. The method according to claim 1 or 2, The quality assessment result is obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively determining the content of one or more types of ions in the acid solution after treatment.

28. The method according to claim 27, The quality assessment results are obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively assessing the content of Na ions in the acid solution after treatment.

29. The method according to claim 1 or 2, The quality assessment results are obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively determining the content of the following substances in the acid solution after treatment: - One or more compounds containing C, but excluding compounds containing Si; and / or - One or more norbornene, norbornene and / or bicyclopentane; and / or - One or more antioxidants, wherein the antioxidants are selected from the group consisting of: pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and / or butylated hydroxytoluene (BHT); tris(2,4-di-tert-butylphenyl) phosphite; tetra(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4'-dimethyldiphosphite.

30. The method according to claim 1 or 2, The quality assessment results are obtained by quantitatively leaching one or more types of ions and / or compounds from at least a portion of the acid-treated surface, and by quantitatively determining the content of the following substances in the acid solution after treatment: - One or more antioxidants, wherein the antioxidant is a phenolic antioxidant.

31. The method according to claim 30, The antioxidant mentioned above is pentaerythritol tetra(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.

32. The method according to claim 1 or 2, comprising the following steps: - Use the obtained quality assessment results to evaluate the suitability of the coated drug container for storing drug solutions; and / or - Use the obtained quality assessment results to evaluate the stability of the coating on the coated drug container; and / or - Link and / or associate the obtained quality assessment results with the coated drug container.

33. The method according to claim 1 or 2, comprising the following steps: - The first and second coated drug containers are produced using the same manufacturing method; - Quantitatively measure the leaching of the first coated drug container to obtain the quality assessment results of the first coated drug container; and - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the stored solution, and / or use the quality assessment results for the quality control of the first and / or second coated drug containers; and / or - Apply and / or use the quality assessment results of the first-coated drug container to determine the suitability of the second-coated drug container for the stored solution, wherein the first-coated drug container exhibits leaching of one or more types of ions and / or compounds <90% relative to the hydrolysis resistance limit of Class 1 glass containers; and / or - The suitability of the second-coated drug container for the stored solution is determined by applying and / or using the quality assessment results of the first-coated drug container, wherein the first-coated drug container exhibits leaching of one or more types of ions and / or compounds <90% relative to the maximum limit in the hydrolysis resistance test of the container surface according to ISO 4802-2:2016(E), Section 9.2, HCF1 and HCF2 classes; and / or - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the stored solution, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 10.00 mg / L.

34. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, and / or use the quality assessment results for the quality control of the first and / or second coated drug containers; and / or - Apply and / or use the quality assessment results of the first-coated drug container to determine the suitability of the second-coated drug container for the solution stored in the second-coated drug container, wherein the first-coated drug container exhibits leaching of one or more types of ions and / or compounds <50% relative to the hydrolysis resistance limit of Class 1 glass containers; and / or - Apply and / or use the quality assessment results of the first-coated drug container to determine the suitability of the second-coated drug container for the solution stored in the second-coated drug container, wherein the first-coated drug container exhibits leaching of one or more types of ions and / or compounds <50% relative to the maximum limit in the hydrolysis resistance test of the container surface according to ISO 4802-2:2016(E), Section 9.2, HCF1 and HCF2 classes of ISO 4802-2:2016(E); and / or - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 5.00 mg / L.

35. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first-coated drug container to determine the suitability of the second-coated drug container for the solution stored in the second-coated drug container, wherein the first-coated drug container exhibits leaching of one or more types of ions and / or compounds <30% relative to the hydrolysis resistance limit of Class 1 glass containers; and / or - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds <30% relative to the maximum limit in the hydrolysis resistance test of the container surface according to ISO 4802-2:2016(E), Section 9.2, HCF1 and HCF2 classes of ISO 4802-2:2016(E); and / or - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 4.5 mg / L.

36. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 4.1 mg / L.

37. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 3.2 mg / L.

38. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 2.5 mg / L.

39. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 2.0 mg / L.

40. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 1.5 mg / L.

41. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 1.2 mg / L.

42. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 1.0 mg / L.

43. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.75 mg / L.

44. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.50 mg / L.

45. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.40 mg / L.

46. ​​The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.30 mg / L.

47. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.2 mg / L.

48. The method of claim 33, wherein - Apply and / or use the quality assessment results of the first coated drug container to determine the suitability of the second coated drug container for the solution stored in the second coated drug container, wherein the first coated drug container exhibits leaching of one or more types of ions and / or compounds below 0.1 mg / L.

49. Use of the quality assessment results obtainable by the method according to any one of claims 1 to 48 for evaluating the suitability of the coated drug container for storing a drug solution and / or the quality control of the production of the coated drug container.

50. A coated drug container, The coating can be obtained using the CVD method. The leaching of one or more types of ions and / or compounds can be obtained by the method according to any one of claims 1 to 48, and The leaching of one or more types of ions and / or compounds is below 5.00 mg / L.

51. The coated drug container according to claim 50, The leaching of one or more types of ions and / or compounds that can be obtained is a; Where a ≤ b*c; If 0.9 × the overflow volume of the container is ≤ 1 ml, then b is 5.00 mg / l. If 0.9 × the overflow volume of the container > 1 ml and ≤ 2 ml, then b is 4.50 mg / l. If 0.9 × the overflow volume of the container > 2 ml and ≤ 3 ml, then b is 4.10 mg / l. If 0.9 × the overflow volume of the container is greater than 3 ml and less than or equal to 5 ml, then b is 3.20 mg / L. If 0.9 × the overflow volume of the container is greater than 5 ml and less than or equal to 10 ml, then b is 2.50 mg / L. If 0.9 × the overflow volume of the container is greater than 10 ml and less than or equal to 20 ml, then b is 2.00 mg / L. If 0.9 × the overflow volume of the container is greater than 20 ml and less than or equal to 50 ml, then b is 1.50 mg / L. If 0.9 × the overflow volume of the container is greater than 50 ml and less than or equal to 100 ml, then b is 1.20 mg / l. If 0.9 × the overflow volume of the container is greater than 100 ml and less than or equal to 200 ml, then b is 1.00 mg / l. Where 0.9 × the overflow volume of the container is >200 ml and ≤500 ml, then b is 0.75 mg / l; and Where 0.9 × the overflow volume of the container > 500 ml, then b is 0.50 mg / l; and Where c is 1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.15, 0.10, 0.08, or 0.

05.

52. The coated drug container according to claim 50 or 51, The coated drug container includes an inner surface and an outer surface, wherein at least a portion of the inner surface is coated with a coating; and The coated drug container exhibits the following equation: i / o ≤ d With [mg / cm 2 ] / [mg / cm 2 The d values, in units of 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.14, 0.10, or 0.07, are... Where i represents the leaching of one or more types of ions and / or compounds, in mg / cm³. 2 ;and Where 'o' represents the leaching of one or more types of ions and / or compounds from the substrate of the coated drug container, expressed in mg / cm³. 2 .

53. A kit comprising: i) A coated drug container according to any one of claims 50 to 52, wherein the coating can be obtained by a CVD method, and ii) A data table or storage medium comprising quality assessment results obtainable by the method according to any one of claims 1 to 48.

Images