Method of making coated container

Abstract

To provide a method of making a coated container, e.g. a syringe, particularly a method of making a container with a lubricant coating on an inner surface.SOLUTION: A method of making a coated container 1 comprises the steps of: providing a container comprising a hollow cylindrical body 7 having a wall surrounding a lumen, the hollow cylindrical body having at least one opening 4; inserting an application body 20 into the lumen through the opening; applying a coating composition 8 to the application body such that the coating composition contacts at least a section of an inner surface of the wall; depositing the coating composition on a deposition area of the inner surface of the wall by moving the application body relative to the hollow cylindrical body; and retracting the application body from the lumen through the opening, where a size of the application body is such that a circumferential gap is present between the application body and the inner surface of the wall during the depositing step.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure relates to methods of making coated containers, such as syringes. In particular, the present disclosure relates to methods of making containers having a lubricant coating on their interior surfaces. The present disclosure also relates to coated containers.

[0002] Background technology Pharmaceutical containers must meet very stringent requirements, including resistance to breakage and leakage. These containers must also be optically flawless so as not to destroy patient or physician confidence in the quality of the pharmaceutical composition contained therein.

[0003] Some pharmaceutical containers, such as syringes, require a smooth movement of the stopper to expel the contents of the container. To achieve this goal, it may be necessary to apply a coating to the inner surface of the pharmaceutical container. Any coating applied to the interface between the container and the stopper improves the smooth movement, and it is desirable that inhomogeneity does not affect this smooth movement of the stopper. The stopper movement should be very uniform, i.e., should not change abruptly along the path of stopper movement. Otherwise, abrupt changes in sliding force would prevent easy and smooth administration of the pharmaceutical composition from the container.

[0004] Pharmaceutical containers are needed in vast quantities. Simple and robust manufacturing techniques are important to facilitate the production of such containers in the millions or even billions. For example, prefilled syringes are a type of pharmaceutical container that has received significant attention in recent years. Market research indicates that the prefilled syringe market is expanding significantly. Demand for prefilled syringes is driven by a variety of factors, including increased vaccine production and the adoption of self-administered biologics for chronic conditions. According to a recent study, sales of prefilled syringes are expected to grow at a rate of approximately 9% annually through 2027, reaching a value of approximately US$9 billion.

[0005] There is a need for pharmaceutical containers and manufacturing methods that meet one or more of the above objectives.

[0006] Summary of the Invention In a first aspect, the present disclosure provides a method of making a coated container, comprising: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, The size of the application body is such that there is a circumferential gap between the application body and the volume region during the deposition step.

[0007] Prior art methods for producing coated containers include spray coating, which is extremely difficult to control and, as a result, does not achieve a completely uniform coating layer. Other methods rely on a hemispherical applicator inserted into the container so that it contacts the interior wall of the container. After insertion, a liquid coating composition is applied to the applicator, dispensing the coating composition as the applicator is retracted from the container.

[0008] In contrast to "press-fit" coating processes, the disclosed method is characterized by a circumferential gap between the application body and the deposition area during the deposition step; in particular, the application body does not contact the inner surface of the hollow cylinder. No press-fit is used, i.e., the application body is not packed into the hollow cylinder, but a gap is left. This gap allows the coating composition applied to the application body to reach or contact at least a portion of the inner surface of the wall, and the application body thereby bridges the gap between the application body and the inner surface, forming a so-called capillary bridge.

[0009] This capillary bridge facilitates a completely different method of coating a container compared to indentation. The inventors hypothesize that in the former process, the coating composition flows down the inner surface of the hollow cylinder as a free-flowing film. In contrast, the capillary bridge technique deposits the silicone cocktail on the surface like a blanket on a bed. Thus, most of the fluid is dragged away by the moving applicator, while only a thin liquid layer remains on the inner surface. Due to drag forces, a constant stress exists along the liquid film. This certainly reduces the tendency for greater accumulation of the coating composition compared to films prepared by indentation. While not wishing to be bound by this theory, the inventors believe this contributes to the superior coating quality achievable with this capillary bridge technique.

[0010] In a second aspect, the present disclosure provides a coated container, optionally obtained or obtainable by a method according to aspect 1, comprising a hollow cylindrical body having a wall surrounding a lumen, the hollow cylindrical body having at least one opening, and at least a portion of an inner surface of the wall comprising a coating; The average coating thickness is between 100 and 3000 nm, and The total area of ​​excess coating thickness is less than 10% of the coating area, with excess coating thickness being defined as an area exhibiting a coating thickness greater than two times the average coating thickness; Concerning coated containers.

[0011] As described above, the method of the present disclosure allows the production of coated containers with excellent film properties. The coating has a low coating thickness variation, i.e., the proportion of areas with excessive thickness or very thin thickness is small. This achieves good and uniform sliding properties of pharmaceutical containers, especially stoppers used in pre-filled syringes. A uniform film thickness also reduces the maximum value of local stress, thereby reducing the tendency of the coating to be scraped off from the inner surface due to the movement of the stopper. Therefore, the coating technology used in the present disclosure contributes to reducing the potential contamination of pharmaceutical preparations in containers, especially when stored in pre-filled syringes for a long time. [Brief explanation of the drawings]

[0012] [Figure 1] 1 illustrates an exemplary medication container. [Figure 2] 1 is a schematic diagram of some of the method steps of the disclosed method. [Figure 3A] 1 is a schematic view of an applicator body inserted into a hollow cylinder in a press-fit mode. [Figure 3B] 1 is a schematic diagram of an applicator body inserted into a hollow cylinder having a circumferential gap according to the present disclosure. [Figure 4A] 1 shows the thickness distribution of a coating applied by the press-fit technique. [Figure 4B] 1 shows the thickness distribution of a coating applied using the capillary bridge technique of the present disclosure. [Figure 5A] 1 is a schematic diagram of an applicator body according to the present disclosure. [Figure 5B] 1 is a diagram of a capillary bridge shape obtained with the method of the present disclosure. FIG.

[0013] MODE FOR CARRYING OUT THE INVENTION method In one embodiment, the present disclosure provides a method of making a coated container, comprising: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, wherein the size of the applicator body is such that there is a circumferential gap between the applicator body and the inner surface during the deposition step.

[0014] The pharmaceutical container and / or wall may be partially or entirely made of a material suitable for primary pharmaceutical packaging. Suitable materials include glass or polymer. The glass may be a silicate glass, such as a borosilicate glass. The polymer may be an amorphous polymer. Transparent polymers are preferred. Suitable polymers may be selected from the group consisting of cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polyethylene terephthalate (PET), polycarbonate (PC), polypropylene (PP), and methyl methacrylate acrylonitrile butadiene styrene polymer (MABS). These polymers have the advantages of low density, high transparency, low birefringence, extremely low water absorption, excellent water vapor barrier properties, high stiffness, strength, and hardness, excellent biocompatibility, very good resistance to acids and alkalis, and very good melt processability.

[0015] The walls and / or the pharmaceutical container may be made of a polymer, optionally with a low density compared to glass, e.g., 0.90-1.20 g / cm 3 , or over 1.00 to 1.10 g / cm 3A polymer having a density of 0.01 mm is selected. If a low-density material is used, transportation costs can be reduced. Density can be determined using the method described in ISO 1183-1:2013-04. Wall thickness can be 1 mm to 2.5 mm, or 1.2 mm to 2 mm, or 1.3 mm to 1.9 mm.

[0016] In embodiments, the applicator body is inserted and retracted through the same opening. When the container is a syringe, this is typically an opening on the flange side. In certain embodiments, the opening through which the applicator body is retracted faces downward. Typically, the direction of movement in the deposition step is the same as the retraction direction in the retraction step of the method. Thus, in some embodiments, at least a portion of the coating composition is deposited on the deposition area by the downward movement of the applicator body. During this movement, a capillary bridge bridges the gap between the applicator body and the inner surface of the wall, thereby depositing the coating composition very uniformly on the deposition area. In the present disclosure, a "deposition area" refers to a portion of the inner surface of the wall where a coating is desired and / or formed during the coating process by depositing the coating composition. It should be understood that the insertion, movement, and retraction of the applicator body include cases where the applicator body is stationary, where the container is moved, or where both the applicator body and the container are moved. In other words, the indicated movements should be understood as relative movements. In some embodiments, more than 80% (vol / vol) of the coating composition, or substantially all of the coating composition, is deposited on the deposition area by the downward movement of the applicator body.

[0017] The insertion of the applicator body is completed when the applicator body is in the initial position. The "initial position" is the position within the cylinder where the step of applying the coating composition to the applicator body is performed. If the deposition of the coating composition is performed with a withdrawal movement, i.e., in the opposite direction to the insertion, the initial position will be closer to the opposite end of the deposition area compared to the opening through which the applicator body was inserted. If the deposition of the coating composition is performed with a pushing movement, i.e., in the insertion direction, the initial position will be closer to the end of the deposition area adjacent to or close to the opening through which the applicator body was inserted. It has been found that deposition with a withdrawal movement is more advantageous than a pushing movement in that a more homogeneous coating is obtained.

[0018] Optionally, the gap may be an annular gap having an essentially circular cross section. Generally, it is easier to obtain a uniform coating when both the application body and the hollow cylinder have essentially round cross sections. In an embodiment, when the application body is present in the hollow cylinder, it has a circumferential portion closest to the inner surface of the wall. This portion can be referred to as the "equator" of the application body, regardless of whether the application body is spherical or not. The application body can have a spherical, hemispherical, conical, or any other shape suitable for achieving a capillary bridge as discussed herein. Generally, it is desirable for the application body to have an essentially spherical, hemispherical, or conical shape on the equator side where the coating composition is applied to the application body. In one embodiment, the coating composition is applied to the upward-facing side of the application body so that the coating composition can flow downward toward the gap, forming a capillary bridge downward toward the gap. In one embodiment, the application body has a shape whose diameter increases from the upward-facing side toward its equator.

[0019] The size of the circumferential gap can be characterized by the distance D between the application body and the deposition area during the deposition step. The distance D is defined as the average distance between the application body and the deposition area during the deposition step. The "average distance" is the average inner diameter D of the hollow cylinder. ID The average diameter of the applied body D AB It is calculated by subtracting and dividing by 2 (

number

[0020] The relative gap size is D / D AB In one embodiment, D / D AB is 0.0005 to 0.02, 0.001 to 0.01, or 0.0015 to 0.006. Optionally, D / D AB is at least 0.0005, at least 0.001, at least 0.0015, or at least 0.002. In certain embodiments, D / D AB is at most 0.02, at most 0.01, at most 0.08, at most 0.06, or at most 0.04.

[0021] It is useful to select a container having a hollow cylinder that meets strict geometric parameters. In one embodiment, the cylinder has a total inner diameter variation in the deposition region of at most 2D, at most 1.5D, or at most D. Optionally, the total inner diameter variation is less than 0.10 mm, less than 0.08 mm, less than 0.06 mm, or less than 0.04 mm. The smaller the total inner diameter variation, the better. However, in some embodiments, providing a container with extremely small total inner diameter variation may not be economically feasible. Thus, in one embodiment, the total inner diameter variation may be at least 0.0001 mm, at least 0.001 mm, or at least 0.01 mm. For example, the total inner diameter variation may be in the range of 0.0001 mm to less than 0.10 mm, 0.001 mm to less than 0.08 mm, or 0.01 mm to less than 0.04 mm.

[0022] To facilitate highly uniform coating, the coating body should also meet strict quality standards. For example, the coating body may have a total outer diameter variation at its equator of up to 2D, up to 1.5D, or up to D. Optionally, the total outer diameter variation is less than 0.20 mm, less than 0.15 mm, less than 0.10 mm, or less than 0.04 mm. The smaller the total outer diameter variation, the better. However, in some embodiments, providing a coating body with extremely small total outer diameter variation may not be economically feasible. Thus, in one embodiment, the total outer diameter variation may be at least 0.0001 mm, at least 0.001 mm, or at least 0.003 mm. For example, the total outer diameter variation may be in the range of 0.0001 mm to less than 0.20 mm, 0.001 mm to less than 0.15 mm, or 0.003 mm to less than 0.04 mm.

[0023] In one embodiment, the coating body comprises or consists of a polymer material. The coating body may be coated or uncoated. In general, the material of the coating body is not limited as long as it is available with sufficient dimensional accuracy (see above). In one embodiment, at least a portion of the surface of the coating body that comes into contact with the coating composition during the method of the present disclosure is made of a fluorinated polymer such as PTFE or coated with a fluorinated polymer.

[0024] In one embodiment, the application body and / or the coating on the application body comprises a resin such as polytetrafluoroethylene (PTFE), densified expanded polytetrafluoroethylene (ePTFE), tetrafluoroethylene (TFE), tetrafluoroethylene-perfluoroethylene copolymer, tetrafluoroethylene-hexafluoropropylene copolymer, tetrafluoroethylene-ethylene copolymer, trichlorotrifluoroethylene, polyvinylidene fluoride, polyvinyl fluoride, perfluoropropyl vinyl ether, perfluoroalkoxy polymer, and copolymers, blends, and combinations thereof. The coating may also be formed by a layer comprising polyethylene, polypropylene, polyparaxylxylene, polylactic acid, and copolymers, blends, and combinations thereof. PTFE coating is one coating option. These coatings reduce the coefficient of friction of the body surface on the inner surface of the hollow cylinder.

[0025] At least a portion of the surface of the application body, such as the portion of the surface in contact with the capillary bridge, may have a water contact angle of at least 100°, or even at least 110°. The surface may be superhydrophobic.

[0026] The inner surface of the hollow cylinder can have a surface energy of at most 45 mN / m, at most 40 mN / m, or at most 35 mN / m. Optionally, the surface energy is at least 15 mN / m, at least 20 mN / m, or at least 25 mN / m. For example, the surface energy of the inner surface can be in the range of 15 mN / m to 45 mN / m, 20 mN / m to 40 mN / m, or 25 mN / m to 35 mN / m. Preferably, the surface energy of the inner surface is higher than the surface energy of the surface of the application body on which the capillary bridge is formed. For example, the surface energy of the application body can be at most 25 mN / m, or at most 20 mN / m. Optionally, the surface energy of the application body can be at least 10 mN / m, or at least 15 mN / m. In one embodiment, the surface energy of the coated body on which the capillary bridge is formed ranges from 10 mN / m to 25 mN / m, or from 15 mN / m to 20 mN / m. In one embodiment, the surface energy of the inner surface of the hollow cylinder exceeds the surface energy of the coated body by at least 40%, at least 50%, or at least 60%. The surface energy can be measured indirectly by calculating a value using the Owens-Wendt-Rabel-Kaelble (OWRK) method from contact angle measurements in accordance with DIN 55660-2:2011-12, Chapter 6.2. The surface energy of the coating composition may be less than the surface energy of the coated body and / or the inner surface of the hollow cylinder. Optionally, the surface energy of the coating composition is less than 20 mN / m, less than 17 mN / m, or less than 15 mN / m. In one embodiment, the surface energy of the coating composition is at least 5 mN / m, at least 8 mN / m, or at least 10 mN / m. For example, the surface energy of the coating composition can be in the range of 5 mN / m to 20 mN / m, 8 mN / m to 17 mN / m, or 10 mN / m to 15 mN / m. Appropriate surface energy contributes to the formation of capillary bridges.

[0027] In one embodiment, the application body includes one or more ducts suitable for delivering the coating composition through the application body. The one or more ducts are useful because they eliminate the need to place a volume of coating composition within the hollow cylinder prior to insertion of the application body. Instead, the application body can be appropriately inserted and positioned within the lumen before the coating composition is applied. In one embodiment, the one or more ducts terminate near or at the tip of the application body. The tip of the application body is typically the top of the application body when the coating composition is applied. From there, the coating composition can flow toward the circumferential gap, bridging the gap and forming a capillary bridge. Thus, applying the coating composition to the application body can include delivering the coating composition through the one or more ducts. Typically, the one or more ducts terminate above the equator of the application body, allowing the coating composition to flow downward over the application body. Applying the coating composition to the application body can include delivering the coating composition to the top section of the application body and allowing the coating composition to flow downward over the application body. In one embodiment, the applicator body includes at least two, at least three, at least four, or at least six ducts. Optionally, the number of ducts may range up to 24, up to 20, up to 16, or up to 12. For example, the applicator body may include 1 to 24, 2 to 20, 4 to 16, or 6 to 12 ducts. The ducts may be positioned throughout the applicator body to support uniform distribution of the coating composition.

[0028] The step of applying the coating composition to the application body may include delivering the coating composition to a section of the application body and allowing the coating composition to build a capillary bridge between the application body and the inner surface of the wall.

[0029] As described above, the coating composition is applied to the application body so that the coating composition contacts at least a section of the inner surface of the wall. This requires that the coating composition be close enough to the inner surface of the wall to span the circumferential gap. In one embodiment, the size of the circumferential gap is such that the coating composition forms a capillary bridge spanning the circumferential gap during the deposition step. If the gap size is small enough to allow for a capillary bridge during the deposition step, particularly during the entire deposition step, a highly uniform coating can be obtained. On the other hand, if the gap size is too small, the application body may inadvertently contact the inner surface in the deposition area, preventing uniform deposition of the coating composition.

[0030] In one embodiment, the volume of coating composition initially applied to the application body is sufficient to bridge the gap throughout the deposition step. In another embodiment, one or more additional volumetric quantities of coating composition are applied to the application body during the deposition step, e.g., to replenish the volume of the coating composition, so that the capillary bridge remains intact throughout the deposition step.

[0031] In one embodiment, the total volume of the coating composition applied to the application body initially, and optionally during the deposition step, is at least 2 μl, at least 5 μl, at least 10 μl, at least 25 μl, or at least 50 μl. Optionally, this volume may be up to 200 μl, up to 100 μl, or up to 90 μl. Of course, the exact volume of the coating composition depends on the deposition area and the desired thickness of the coating. For example, the total volume of the coating composition may be 2 μl to 200 μl, or 5 μl to 100 μl.

[0032] In one embodiment, the movement speed of the applicator body during deposition of the coating composition is equal to or less than the flow rate of the coating composition in the direction of movement of the applicator body. As described above, the applicator body moves relative to the hollow cylinder during deposition of the coating composition. During this step, the capillary bridges should remain intact to achieve the most uniform results. If the applicator body moves too quickly, a significant portion of the coating composition may revert to free-flowing motion, potentially forming riblets on the inner surface. These riblets remain as significant inhomogeneities on the inner surface. Optionally, the movement speed of the applicator body is at least 2 mm / s, at least 4 mm / s, at least 5 mm / s, or at least 10 mm / s. In one embodiment, the movement speed is at most 50 mm / s, at most 30 mm / s, at most 20 mm / s, or at most 15 mm / s. For example, the movement speed of the applicator body is in the range of 2 mm / s to 50 mm / s, 5 mm / s to 30 mm / s, or 10 mm / s to 15 mm / s.

[0033] In one embodiment, the method can further include air flushing the container after depositing the coating composition on the deposition area, which can contribute to evaporation of diluents in the coating composition and help smooth the coating.

[0034] Additionally or alternatively, the method may include a step of curing the coating composition after depositing it on the deposition area to obtain a cured coating. Curing can be used to crosslink and / or polymerize crosslinkable or polymerizable compounds of the coating composition to form the coating. Curing can also contribute to evaporation of diluents from the coating composition.

[0035] The coating composition can be applied to achieve a desired coating thickness. The coating can have an average thickness of 100 nm or more, 200 nm or more, 300 nm or more, 400 nm or more, or 450 nm or more. Optionally, the coating can have an average thickness of up to 3000 nm, up to 2500 nm, up to 2000 nm, up to 1500 nm, up to 1000 nm, or up to 850 nm. An appropriate coating thickness contributes to sealing at low temperatures. In embodiments, the average coating thickness can be 100 nm to 3000 nm, 200 nm to 2000 nm, or 300 nm to 1500 nm, or 400 nm to 1000 nm. Optionally, the stated average coating thickness is present over at least 90%, at least 95%, or at least 99% of the coated area. In embodiments, the average coating thickness is greater than 400 nm, particularly at least 450 nm or at least 500 nm. Exemplary preferred ranges for the average coating thickness are greater than 400 nm to 1500 nm, 450 nm to 1250 nm, or 450 nm to 850 nm.

[0036] The coating composition can be deposited on at least 25% or at least 50% (by area) of the inner surface of the hollow cylinder. The coating can have a beneficial effect on the sliding properties of the stopper on the inner surface of the hollow cylinder. Thus, in some embodiments, the coating composition is deposited on at least 65% or at least 85% (by area) of the inner surface of the hollow cylinder. Optionally, the coating composition is deposited on at least 90% or essentially all of the inner surface of the hollow cylinder.

[0037] As used herein, the term "cure temperature" refers to the effective temperature of a coating for curing the coating. The cure temperature may not be the nominal temperature in an oven, but may be higher than the effective temperature of the coating during curing. Curing may involve polymerizing polymerizable groups, such as polymerizable end groups. Coatings can be cured at cure temperatures below 150°C, below 125°C, or below 110°C. A cure temperature that is too high may result in a brittle coating. On the other hand, a cure temperature that is too low may not be sufficient to achieve good performance. Thus, in embodiments, the cure temperature may be 50°C or higher, 60°C or higher, or 70°C or higher. Specifically, the cure temperature is the effective temperature for the coating composition. It should not be confused with the nominal oven temperature. The oven temperature may be much higher than the cure temperature because there may not be enough time for the entire oven to equilibrate at the nominal temperature during the cure period. Optionally, the coating may be cured at 50°C to below 150°C, 60°C to below 125°C, or 70°C to below 110°C. A preferred range is 50° C. to less than 110° C. In an embodiment, curing does not involve the application of plasma.

[0038] The curing temperature is held for a time sufficient to achieve the desired degree of cure. Optionally, the curing temperature may be held for at least 2 seconds, at least 3 seconds, at least 4 seconds, or at least 5 seconds. In embodiments, the curing temperature is held for up to 300 seconds, up to 100 seconds, or up to 20 seconds.

[0039] After curing, the average coating thickness may be 100-3000 nm. Additionally or alternatively, after curing, the total area of ​​excess coating thickness is less than 10% of the coating area, with excess coating thickness being defined as an area exhibiting a coating thickness greater than 2x, greater than 1.50, or greater than 1.20 of the average coating thickness. After curing, the coating may contain one or more silicon-organic polymers.

[0040] In one embodiment, the method includes the further step of obtaining a coated container of the present disclosure. In one embodiment, the method includes the further step of obtaining a container having a coating as described in more detail below.

[0041] The coating composition can be cured at a cure temperature below 150°C, below 125°C, or below 110°C. A cure temperature that is too high may result in a brittle coating. On the other hand, a cure temperature that is too low may not be sufficient to provide good mechanical resistance to the coating. Thus, in embodiments, the cure temperature may be 50°C or higher, 60°C or higher, or 70°C or higher. Specifically, the cure temperature is the effective temperature for the coating composition. This should not be confused with the nominal oven temperature. The oven temperature may be much higher than the cure temperature because there may not be enough time for the entire oven to equilibrate to the nominal temperature during the cure period. Optionally, the coating may be cured at 50°C to below 150°C, 60°C to below 125°C, or 70°C to below 110°C. The preferred range is 50°C to below 110°C.

[0042] In embodiments, the coating can be or is obtained by applying a coating composition disclosed herein to at least a portion of a surface (e.g., an interior surface) of a container and curing the coating composition on the surface.

[0043] The present disclosure is not particularly limited with respect to the container volume. In one embodiment, the hollow cylinder encloses a volume of at least 0.10 ml, at least 0.50 ml, or at least 1.00 ml. Optionally, the volume may be up to 1,000 ml, up to 200 ml, up to 100 ml, or up to 25 ml. In an embodiment, the volume ranges from 0.1 ml to 1,000 ml, 0.50 ml to 200 ml, or 1.00 ml to 25 ml. In one embodiment, the hollow cylinder encloses a volume of less than 10.0 ml.

[0044] The hollow cylinder has a lumen surrounded by a wall, and the wall can have a wall thickness of at least 0.50 mm, at least 0.80 mm, or at least 1.00 mm. Optionally, the wall thickness can be in the range of up to 10.0 mm, up to 8.0 mm, up to 5.0 mm, or up to 4.0 mm. In embodiments, the wall thickness is 0.50 to 10.0 mm, 0.80 mm to 8.0 mm, or 1.00 mm to 4.00 mm. As used herein, the term "wall thickness" refers to the shortest distance between the inner and outer surfaces of the hollow cylinder.

[0045] As used herein, the term "outer diameter" refers to the maximum distance between two points on the outer surface of a hollow cylinder, the two points being connected by a line perpendicular to and intersecting the longitudinal axis of the hollow cylinder. As used herein, the term "inner diameter" refers to the maximum distance between two points on the inner surface of a hollow cylinder, the two points being connected by a line perpendicular to and intersecting the longitudinal axis of the hollow cylinder.

[0046] In a first specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of polymers such as COC or COP; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body includes one or more ducts suitable for delivering the coating composition through the application body; and The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm.

[0047] In a second specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of polymers such as COC or COP; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; The total volume of the coating composition applied to the application body is 5 μl to 100 μl; and The speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body.

[0048] In a third specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of polymers such as COC or COP; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; The total volume of the coating composition applied to the application body is 5 μl to 100 μl; and the speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body; The coating composition comprises polysiloxane structural units or compounds.

[0049] In a fourth specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of polymers such as COC or COP; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; the total volume of the coating composition applied to the application body initially, and optionally during the deposition step, is between 5 μl and 100 μl; the speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body; the coating composition comprises polysiloxane structural units or compounds; and The surface energy of the inner surface is higher than the surface energy of the surface of the application body on which the capillary bridge is formed.

[0050] In a fifth specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of glass; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body includes one or more ducts suitable for delivering the coating composition through the application body; and The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm.

[0051] In a sixth specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of glass; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; The total volume of the coating composition applied to the application body is 5 μl to 100 μl; and The speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body.

[0052] In a seventh specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of glass; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; The total volume of the coating composition applied to the application body is 5 μl to 100 μl; and the speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body; The coating composition comprises polysiloxane structural units or compounds.

[0053] In an eighth specific embodiment, the method comprises: providing a container including a hollow cylinder having a wall surrounding a lumen, the hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area on the inner surface of the wall by moving an applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, the applicator body is sized such that there is a circumferential gap between the applicator body and the inner surface during the deposition step; The walls are made of glass; The downward movement of the applicator deposits at least a portion of the coating composition on the deposition area; the application body comprises one or more ducts adapted to deliver the coating composition through the application body; The size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step of less than 0.10 mm; the total volume of the coating composition applied to the application body initially, and optionally during the deposition step, is between 5 μl and 100 μl; the speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body; the coating composition comprises polysiloxane structural units or compounds; and The surface energy of the inner surface is higher than the surface energy of the surface of the application body on which the capillary bridge is formed.

[0054] Coating Composition The coating composition may contain or consist of the raw materials necessary to obtain the coating described in this disclosure. The coating composition may contain one or more silicon-organic materials, such as polymers or oligomers. For example, the coating composition may include polysiloxane structural units or compounds. The polysiloxane compounds of the coating composition may include crosslinkable and / or non-crosslinkable polysiloxane compounds. In one embodiment, the polysiloxane compound is a polyalkylsiloxane compound, such as a polydialkylsiloxane compound. Optionally, one or more of the alkyl groups in the polyalkylsiloxane or polydialkylsiloxane are independently selected from branched or unbranched C1-C8 alkyl groups. Additionally, the coating composition may include a catalyst and / or a diluent.

[0055] A polysiloxane compound is considered "crosslinkable" if it contains one or more (especially two) groups that are polymerizable or crosslinkable under the curing conditions of the present disclosure, particularly at cure temperatures below 150° C. and cure times below 3000 seconds. A polysiloxane compound is considered "non-crosslinkable" if it does not contain chemical structures that are polymerizable or crosslinkable under the curing conditions of the present disclosure, particularly at cure temperatures below 150° C. and cure times below 3000 seconds.

[0056] In one embodiment, the coating composition comprises: one or more crosslinkable polydialkylsiloxane compounds, and one or more non-crosslinkable polysiloxane compounds Includes.

[0057] Optionally, the coating composition comprises: one or more crosslinkable polydialkylsiloxane compounds, one or more non-crosslinkable polysiloxane compounds, and one or more crosslinked polysiloxane compounds Includes.

[0058] Crosslinked polysiloxane compounds The crosslinked polysiloxane compound is suitable for reacting with the crosslinkable polysiloxane compound, preferably in a hydrosilylation reaction, to form a polysiloxane network under the conditions of the present disclosure (particularly at cure temperatures of less than 150° C. and cure times of less than 3000 seconds).

[0059] The crosslinked polysiloxane compound may include alkylsiloxane monomer units, such as dialkylsiloxane monomer units. Optionally, one or more of the alkyl groups of the monomers in the crosslinked polysiloxane compound are independently selected from branched or unbranched C1-C8 alkyl groups. The alkyl groups may be linear alkyl groups. For example, the alkyl groups may be independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl groups. Optionally, the alkyl groups are independently selected from methyl and ethyl.

[0060] In some embodiments, the crosslinked polysiloxane compound is a polysiloxane having Si-H groups. In an exemplary embodiment, the crosslinked polysiloxane compound is a copolymer having dimethylsiloxane and methylhydrosiloxane monomer units. In this case, it has been found advantageous to use a copolymer having the following structure (m is an integer greater than or equal to 1, n is an integer greater than or equal to 1; n may be greater than or equal to 2): [ka] .

[0061] Optionally, the crosslinked polysiloxane is a copolymer having, in particular, dialkylsiloxane and alkylhydrosiloxane monomer units. The alkyl groups in the alkylhydrosiloxane monomer units may be selected from branched or unbranched C1-C8 alkyl groups. The alkyl groups may be linear alkyl groups. For example, the alkyl groups may be independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl groups. Optionally, the alkyl groups are independently selected from methyl and ethyl.

[0062] The crosslinked polysiloxane may be present in the coating composition at a concentration of 0.10 to 1.50 wt%, 0.10 to 1.00 wt%, or 0.10 to 0.60 wt%. In embodiments, the concentration of the crosslinked polysiloxane in the coating composition should not exceed 1.50 wt%, 1.00 wt%, or 0.60 wt%. A minimum amount of 0.10 wt% is preferred.

[0063] Non-crosslinkable polysiloxane compounds The coating composition may include two or more types of non-crosslinked polysiloxane compounds, such as at least two or at least three types. These types may have different viscosities. In some embodiments, the coating includes a high-viscosity non-crosslinked polysiloxane compound having a viscosity greater than 10,000 cSt and / or a low-viscosity non-crosslinked polysiloxane compound having a viscosity of 10,000 cSt or less. The viscosity of the polysiloxane compound is preferably at 23°C and 10 s. -1 The viscosity can be determined in accordance with DIN EN ISO 3219:1993 using a concentric cylinder system at a shear rate of 1000 psi. Optionally, the high-viscosity non-crosslinked polysiloxane compound has a viscosity of at least 15,000 cSt, and / or the low-viscosity non-crosslinked polysiloxane compound has a viscosity of 5,000 cSt or less.

[0064] The weight ratio (mass) of the low-viscosity non-crosslinked polysiloxane compound to the high-viscosity non-crosslinked polysiloxane compound 高 :mass 低 ) can be at least 0.10, at least 0.50, at least 1.00, at least 1.50, or at least 2.00. In some embodiments, this ratio can range up to 5.00, up to 4.00, or up to 3.00. For example, the weight ratio of the low-viscosity non-crosslinked polysiloxane compound to the high-viscosity non-crosslinked polysiloxane compound can range from 0.10 to 5.00, 0.50 to 4.00, or 1.00 to 3.00.

[0065] Optionally, the low-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of 1,200 to 30,000 g / mol, and / or the high-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of 15,000 to 300,000 g / mol. In one embodiment, the high-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of 32,000 to 210,000 g / mol, or 100,000 to 150,000 g / mol. In one embodiment, the low-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of 5,000 to 25,000 g / mol, or 10,000 to 20,000 g / mol.

[0066] In embodiments, the low-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of at least 1,200 g / mol, at least 5,000 g / mol, or at least 10,000 g / mol. The weight average molecular weight may range up to 30,000 g / mol, up to 25,000 g / mol, or up to 20,000 g / mol.

[0067] In embodiments, the high-viscosity non-crosslinked polysiloxane compound has a weight average molecular weight of at least 15,000 g / mol, at least 32,000 g / mol, or at least 100,000 g / mol. The weight average molecular weight can range up to 300,000 g / mol, up to 210,000 g / mol, or up to 150,000 g / mol. The weight average molecular weight can be determined by gel permeation chromatography (GPC).

[0068] Polydimethylsiloxane is particularly suitable as the non-crosslinkable polysiloxane compound.

[0069] Crosslinkable polysiloxane compounds The crosslinkable polysiloxane compound may be crosslinkable through one or more, preferably two, end groups. In particular, the end groups may have double bonds, making them available for hydrosilylation reactions under the conditions of the present disclosure (especially curing temperatures of less than 150°C and curing times of less than 3000 seconds). The end groups may be selected from vinyl, acrylic, methacrylic, styrene, and combinations thereof.

[0070] In one embodiment, the crosslinkable polysiloxane compound and the crosslinked polysiloxane compound can form a hydrosilylation reaction product under the conditions of the present disclosure (particularly a cure temperature of less than 150°C and a cure time of less than 3000 seconds). Suitable crosslinkable polysiloxane compounds are vinyl-polysiloxane compounds. The crosslinked polysiloxane may be crosslinked by reaction of multiple Si-H groups with the vinyl groups of the crosslinkable polysiloxane. The reaction may be platinum catalyzed.

[0071] The crosslinkable polysiloxane compound may include alkylsiloxane monomer units, such as dialkylsiloxane monomer units. Optionally, one or more of the alkyl groups of the monomers in the crosslinkable polysiloxane compound are independently selected from branched or unbranched C1-C8 alkyl groups. The alkyl groups may be linear alkyl groups. For example, the alkyl groups may be independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl groups. Optionally, the alkyl groups are independently selected from methyl and ethyl.

[0072] Diluent The coating composition may further comprise one or more diluents.In the context of the present disclosure, the diluent can be a Si-containing solvent in which the crosslinkable polysiloxane compound and the non-crosslinkable polysiloxane compound are soluble.In order to ensure good solubility of the polysiloxane compound, a non-polar solvent can be used as a diluent.In this case, it has been found that it is useful to use a silicon-organic compound having up to 6 silicon atoms as a diluent.

[0073] Exemplary diluents are as follows: Cyclic silicones, such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, tetramethylcyclotetrasiloxane, pentamethylcyclopentasiloxane, hexamethyldisiloxane (HMDSO), octamethyltrisiloxane, Decamethyltetrasiloxane.

[0074] Mixtures containing one or more of the above materials may also be used as diluents, among others.

[0075] The coating composition is a liquid. In embodiments, the coating composition has a viscosity of 1.0 to 50 mPas, 2.0 to 25 mPas, or 3.0 to 15 mPas. Optionally, the coating composition has a viscosity of at least 1.0 mPas, at least 2.0 mPas, at least 3.0 mPas, or at least 3.5 mPas. For example, the viscosity of the coating composition can range up to 50 mPas, up to 25 mPas, or up to 15 mPas. The viscosity of the coating composition can be determined according to DIN EN ISO 3219:1993 using a concentric cylinder system at 25°C and a shear rate of 16.8 s-1.

[0076] Catalyst / Inhibitor The coating composition may further comprise a catalyst for the crosslinking reaction of the multi-component compound. A soluble platinum-containing catalyst, such as chloroplatinic acid, may be used. Karstedt's catalyst may be used.

[0077] In some embodiments, the coating composition includes at least one inhibitor to prevent spontaneous crosslinking of the composition, which facilitates handling of the composition prior to application of the coating. The inhibitor can enter into a reversible complex with the catalyst, thereby preventing spontaneous crosslinking of the composition.

[0078] Coating Composition In one embodiment, the coating composition includes a high viscosity non-crosslinked polysiloxane compound, but does not necessarily include a low viscosity non-crosslinked polysiloxane compound.

[0079] In one embodiment, the coating composition comprises the following components: [Table 1]

[0080] In one embodiment, the coating composition comprises the following components in weight percent: [Table 2]

[0081] In certain embodiments, the weight ratio of the crosslinked polysiloxane compound to the crosslinkable polysiloxane compound is at least 0.01, at least 0.015, or at least 0.02. Optionally, this ratio may not exceed 0.5, 0.4, 0.2, or 0.1. In some embodiments, this ratio ranges from 0.01 to 0.5, from 0.015 to 0.4, or from 0.02 to 0.2.

[0082] Optionally, the ratio of the weight of crosslinkable polysiloxane compounds to the weight of non-crosslinkable polysiloxane compounds in the coating composition is less than 3.00, less than 2.50, less than 1.80, or less than 1.20. The ratio of the weight of crosslinkable polysiloxane compounds to the weight of non-crosslinkable polysiloxane compounds in the coating can be at least 0.40, at least 0.60, or at least 0.70. In embodiments, this ratio is in the range of 0.40 to 3.00, 0.60 to 2.50, or 0.70 to 1.80.

[0083] In one embodiment, the coating composition comprises the following components in weight percent: [Table 3]

[0084] In one embodiment, the coating composition comprises the following components in weight percent: [Table 4]

[0085] In one embodiment, the coating composition comprises the following components in weight percent: [Table 5]

[0086] In one embodiment, the coating composition comprises the following components in weight percent: [Table 6]

[0087] More specific coating compositions The crosslinked polysiloxane structural units, the low viscosity non-crosslinked polysiloxane structural units, and / or the high viscosity non-crosslinked polysiloxane structural units may comprise or consist of dialkylsiloxane monomer units, in particular dimethylsiloxane monomer units.

[0088] In some embodiments, the crosslinkable polysiloxane is a vinyl-functionalized polysiloxane, and / or the crosslinked polysiloxane compound is a polysiloxane having Si-H groups. An exemplary embodiment contains a vinyl-functionalized polydimethylsiloxane as the crosslinkable polysiloxane compound, and / or a copolymer having dimethylsiloxane and methylhydrosiloxane monomer units as the crosslinked polysiloxane compound. In this case, it has been found advantageous to use a copolymer having the following structure (m is an integer greater than or equal to 1, n is an integer greater than or equal to 1; n may be greater than or equal to 2): [ka] .

[0089] In a more specific variation, the coating composition comprises the following components: [Table 7]

[0090] In a more specific variation, the coating composition comprises the following components in weight percent: [Table 8]

[0091] In a more specific variation, the coating composition comprises the following components in weight percent: [Table 9]

[0092] In a more specific variation, the coating composition comprises the following components in weight percent: [Table 10]

[0093] In a more specific variation, the coating composition comprises the following components in weight percent: [Table 11]

[0094] In a more specific variation, the coating composition comprises the following components in weight percent: [Table 12]

[0095] Optionally, the crosslinkable polysiloxane structural unit, the low-viscosity non-crosslinkable polysiloxane structural unit, and / or the high-viscosity non-crosslinkable polysiloxane structural unit may comprise a dialkylsiloxane monomer unit, particularly a dimethylsiloxane monomer unit. The crosslinkable polysiloxane structural unit may be crosslinkable via one or more polymerizable end groups.

[0096] Coated containers In one embodiment, the present disclosure relates to a coated container. The coatings described in detail herein can be obtained by the methods described above. The coated container may be obtained or can be obtained by the methods of the present disclosure. The coated container comprises a hollow cylindrical body having a wall surrounding a lumen, the hollow cylindrical body having at least one opening, and at least a portion of the inner surface of the wall comprising a coating.

[0097] The average coating thickness can be from 100 to 3000 nm.

[0098] Optionally, the total area of ​​excess coating thickness is less than 10% of the coating area, where excess coating thickness is defined as an area exhibiting a coating thickness greater than 2 times the average coating thickness, greater than 1.50, or greater than 1.20. In certain embodiments, the total area of ​​excess coating thickness is less than 7%, less than 5%, or less than 3% of the coating area.

[0099] In one embodiment, the coating contains one or more silicon-organic polymers.

[0100] In certain useful embodiments, the total area of ​​insufficient coating thickness is less than 5% of the coating area, and the insufficient coating thickness is an area exhibiting a coating thickness of less than 100 nm or less than 50 nm. The total area of ​​insufficient coating thickness may be less than 3% or less than 2% of the coating area.

[0101] The coated containers of the present disclosure may have a coating comprising one or more crosslinked polysiloxane structural units and one or more non-crosslinked polysiloxane structural units, wherein the ratio of the weight of the crosslinked polysiloxane structural units to the weight of the non-crosslinked polysiloxane structural units in the coating is less than 3.00, and optionally at least 0.40.

[0102] The coating may be disposed on the inner surface of the hollow cylindrical body of the container. The coating may have an average thickness of 100 nm or more, 200 nm or more, 300 nm or more, 400 nm or more, or 450 nm or more. Optionally, the coating may have an average thickness of up to 3000 nm, up to 2000 nm, up to 1500 nm, up to 1000 nm, or up to 850 nm. An appropriate coating thickness contributes to sealing at low temperatures. In embodiments, the average coating thickness may be 100 nm to 3000 nm, 200 nm to 2000 nm, or 300 nm to 1500 nm, or 400 nm to 1000 nm. Optionally, the stated average coating thickness is present over at least 90%, at least 95%, or at least 99% of the coated area. In embodiments, the average coating thickness is greater than 400 nm, particularly at least 450 nm or at least 500 nm. Exemplary preferred ranges for the average coating thickness are greater than 400 nm to 1500 nm, 450 nm to 1250 nm, or 450 nm to 850 nm.

[0103] In embodiments, the hollow cylinder described in this disclosure as part of a container can have an essentially constant inner diameter to allow the stopper to expel essentially all of the composition present within the cylinder, in this context, "essentially constant" includes an inner diameter variation of 200 μm or less, 100 μm or less, or 50 μm or less.

[0104] The container may be any type of container, including a vial, a syringe, or a cartridge. In one embodiment, the container is a syringe or a cartridge.

[0105] The coating may contain one or more silicon-organic polymers. A "silicon-organic polymer" is a polymeric material composed of monomer units, which contain both silicon (Si) and carbon (C) atoms. An example of a silicon-organic polymer is polysiloxane. In embodiments, the coating contains one or more polysiloxane structural units. A "polysiloxane structural unit" can refer to a polysiloxane structure within a larger molecule (e.g., covalently bonded to a larger molecule or part of a larger molecule) or to the polysiloxane molecule itself. For example, a crosslinked polysiloxane structural unit is part of (covalently bonded to) the polymer network, while a non-crosslinked polysiloxane structural unit exists in the coating as a molecule that is not covalently bonded to other molecules in the coating. Thus, the coating may contain crosslinked and / or non-crosslinked polysiloxane structural units. In this context, "crosslinked" means that the polysiloxane structural unit is covalently bonded to the polymer network. Specifically, the term "crosslinked" includes the preferred case where the polysiloxane structure is covalently bonded to other polysiloxane structures, for example, via a polymer backbone. Optionally, the crosslinked polysiloxane structural units are covalently bonded to other polysiloxane structures as a result of a hydrosilylation reaction. The polymer backbone can be formed, for example, by polymerizing a polysiloxane having a polymerizable functional group, such as a vinyl group. In contrast, "non-crosslinked" means that the polysiloxane is not covalently bonded to other polysiloxane structures or to other polysiloxanes in the coating via the polymer backbone.

[0106] In one embodiment, the crosslinked polysiloxane structural unit is crosslinked through one or more, for example, two, end groups. The end groups may be selected from vinyl, acrylic, methacrylic, styrene, and combinations thereof. In one embodiment, the coating comprises a hydrosilylation reaction product of a crosslinkable polysiloxane compound and a crosslinked polysiloxane compound, for example, a vinyl-polysiloxane compound and a polysiloxane having at least two Si—H groups. The crosslinked polysiloxane may crosslink the crosslinkable polysiloxane by reaction of its multiple Si—H groups with the vinyl groups of the crosslinkable polysiloxane. The reaction may be platinum-catalyzed.

[0107] In the present disclosure, "polysiloxane" or "polysiloxane structural unit" may refer to a polyalkylsiloxane structural unit, such as a polydialkylsiloxane structural unit. Optionally, one or more of the alkyl groups in the polyalkylsiloxane or polydialkylsiloxane are independently selected from branched or unbranched C1-C8 alkyl groups. The alkyl groups may be linear alkyl groups. For example, the alkyl groups may be independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl groups. For example, the alkyl groups may be independently selected from methyl and ethyl.

[0108] In one embodiment, the coating comprises both crosslinked polydialkylsiloxane structural units and non-crosslinked polysiloxane structural units. Specifically, the coating may comprise crosslinked polydialkylsiloxane structural units and non-crosslinked polysiloxane structural units, and the non-crosslinked polysiloxane structural units may be polydialkylsiloxane structural units such as one or more silicone oils, i.e., polydimethylsiloxane silicone oils.

[0109] Optionally, the ratio of the weight of crosslinked polysiloxane structural units to the weight of non-crosslinked polysiloxane structural units in the coating is less than 3.00, less than 2.50, less than 1.80, or less than 1.20. The ratio of the weight of crosslinked polysiloxane structural units to the weight of non-crosslinked polysiloxane structural units in the coating can be at least 0.40, at least 0.60, or at least 0.70. In embodiments, this ratio is in the range of 0.40 to 3.00, 0.60 to 2.50, or 0.70 to 1.80.

[0110] The coating may comprise two or more types of non-crosslinked polysiloxane structural units, such as at least two or at least three types. These types may have different viscosities. In some embodiments, the coating comprises high-viscosity non-crosslinked polysiloxane structural units having a viscosity greater than 10,000 cSt and / or low-viscosity non-crosslinked polysiloxane structural units having a viscosity of 10,000 cSt or less. The viscosity of the polysiloxane structural units is at 23°C and 10 s -1 The viscosity can be determined in accordance with DIN EN ISO 3219:1993 using a concentric cylinder system at a shear rate of 1000 psi. Optionally, the high-viscosity non-crosslinked polysiloxane structural units have a viscosity of at least 15,000 cSt and / or the low-viscosity non-crosslinked polysiloxane structural units have a viscosity of 5,000 cSt or less.

[0111] In one embodiment, the coating comprises high viscosity non-crosslinked polysiloxane structural units, but does not necessarily comprise low viscosity non-crosslinked polysiloxane structural units.

[0112] The weight ratio (mass) of the low-viscosity non-crosslinked polysiloxane structural unit to the high-viscosity non-crosslinked polysiloxane structural unit 高 :mass 低) can be at least 0.10, at least 0.50, at least 1.00, at least 1.50, or at least 2.00. In some embodiments, this ratio can range up to 5.00, up to 4.00, or up to 3.00. For example, the weight ratio of low-viscosity non-crosslinked polysiloxane structural units to high-viscosity non-crosslinked polysiloxane structural units can range from 0.10 to 5.00, 0.50 to 4.00, or 1.00 to 3.00.

[0113] The crosslinked polysiloxane structural units, the low viscosity non-crosslinked polysiloxane structural units, and / or the high viscosity non-crosslinked polysiloxane structural units may comprise or consist of dialkylsiloxane monomer units, in particular dimethylsiloxane monomer units.

[0114] Optionally, the low-viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of 1,200 to 30,000 g / mol, and / or the high-viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of 15,000 to 300,000 g / mol. In one embodiment, the high-viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of 32,000 to 210,000 g / mol, or 100,000 to 150,000 g / mol. In one embodiment, the low-viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of 5,000 to 25,000 g / mol, or 10,000 to 20,000 g / mol.

[0115] In embodiments, the low-viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of at least 1,200 g / mol, at least 5,000 g / mol, or at least 10,000 g / mol. The weight average molecular weight may range up to 30,000 g / mol, up to 25,000 g / mol, or up to 20,000 g / mol.

[0116] In embodiments, the high viscosity non-crosslinked polysiloxane structural units have a weight average molecular weight of at least 15,000 g / mol, at least 32,000 g / mol, or at least 100,000 g / mol. The weight average molecular weight may range up to 300,000 g / mol, up to 210,000 g / mol, or up to 150,000 g / mol.

[0117] The coating may have a glass transition temperature of -60°C or less, optionally -70°C or less, e.g., -75°C or less, or -80°C or less. Optionally, the glass transition temperature may be -200°C or more, -150°C or more, -120°C or more, or -100°C or more. The glass transition temperature can be measured using differential scanning calorimetry (DSC) or thermomechanical analysis (TMA). An exemplary method for determining the glass transition temperature of a coating includes thermomechanical analysis in dilatation mode, for example, using a TA Instruments Q400 thermomechanical analyzer. A sample can be prepared by coating a container according to the present disclosure and peeling the coating using a scalpel, and thermomechanical analysis can be performed in dilatation mode, i.e., measuring the expansion or contraction of the sample as a function of temperature. In embodiments, the glass transition temperature of the coating ranges from -200°C to -60°C, -150°C to -70°C, -120°C to -75°C, or -80°C to -100°C. In one embodiment, the glass transition temperature is between -80°C and -90°C.

[0118] The coating can be amorphous or partially crystalline at room temperature. Optionally, the coating has a crystallinity of less than 20% (v / v) at 20°C.

[0119] In embodiments, the coating may have a crystallization temperature range and a melting temperature range determined using differential scanning calorimetry at a temperature ramp rate of 10°C / min, with the crystallization and melting temperature ranges overlapping at temperatures between -75°C and -100°C, particularly -80°C. For example, DSC may be performed at a temperature range of -120°C to -60°C. A suitable instrument is a DSC Q2000 (TA Instruments).

[0120] While not wishing to be bound by this theory, the inventors hypothesize that within this overlap range, both crystalline and molten portions of the coating exist. This is believed to provide the coating with good mechanical resistance. The crystallization temperature range and the melting temperature range are considered to overlap if the crystallization region and the melting peak region span the same temperature range. For example, crystallization may begin at -55°C and end at -95°C, i.e., the exothermic crystallization peak region may range from -55°C to -95°C, and melting may begin at -90°C and end at -40°C, i.e., the endothermic melting peak region may range from -90°C to -40°C. In this example, the overlapping temperature range is -90°C to -55°C. This example satisfies the overlap requirement at temperatures from -75°C to -100°C, since there is overlap at at least one temperature within the indicated range.

[0121] In general, the present disclosure relates to a pharmaceutical composition container comprising a hollow cylindrical body. The container may be configured to receive a stopper that is slidable relative to the hollow cylindrical body from the open end of the container toward the opposite end. In one embodiment, the container has at least two open ends. One open end is adapted to allow the stopper to be inserted. Another open end may be on the opposite side of the container, such as the tip side in the case of a syringe.

[0122] The present disclosure is not particularly limited with respect to the container volume. In one embodiment, the hollow cylinder encloses a volume of at least 0.10 ml, at least 0.50 ml, or at least 1.00 ml. Optionally, the volume may be up to 1,000 ml, up to 200 ml, up to 100 ml, or up to 25 ml. In an embodiment, the volume ranges from 0.1 ml to 1,000 ml, 0.50 ml to 200 ml, or 1.00 ml to 25 ml. In one embodiment, the hollow cylinder encloses a volume of less than 10.0 ml.

[0123] The hollow cylinder has a lumen surrounded by a wall, and the wall can have a wall thickness of at least 0.50 mm, at least 0.80 mm, or at least 1.00 mm. Optionally, the wall thickness can be in the range of up to 10.0 mm, up to 8.0 mm, up to 5.0 mm, or up to 4.0 mm. In embodiments, the wall thickness is 0.50 to 10.0 mm, 0.80 mm to 8.0 mm, or 1.00 mm to 4.00 mm. As used herein, the term "wall thickness" refers to the shortest distance between the inner and outer surfaces of the hollow cylinder.

[0124] As used herein, the term "outer diameter" refers to the maximum distance between two points on the outer surface of a hollow cylinder, the two points being connected by a line perpendicular to and intersecting the longitudinal axis of the hollow cylinder. As used herein, the term "inner diameter" refers to the maximum distance between two points on the inner surface of a hollow cylinder, the two points being connected by a line perpendicular to and intersecting the longitudinal axis of the hollow cylinder.

[0125] The hollow cylindrical body of the container can have an essentially constant inner diameter. This means that the total inner diameter variation is small. "Total inner diameter variation" is the difference between the largest inner diameter of a hollow cylinder and the smallest inner diameter of the same hollow cylinder. Optionally, the total inner diameter variation is less than 0.10 mm, less than 0.08 mm, less than 0.06 mm, or less than 0.04 mm. The smaller the total inner diameter variation, the better. However, in some embodiments, providing a container with extremely small total inner diameter variation may not be economically feasible. Thus, in one embodiment, the total inner diameter variation may be at least 0.0001 mm, at least 0.001 mm, or at least 0.01 mm. For example, the total inner diameter variation may be in the range of 0.0001 mm to less than 0.10 mm, 0.001 mm to less than 0.08 mm, or 0.01 mm to less than 0.04 mm.

[0126] Containers according to embodiments of the present disclosure can have a standard sliding force of 5.0 N or less. The sliding force refers to the force required to push the stopper inside the hollow cylinder, and the release force refers to the force required to cause the initial movement of the stopper inside the hollow cylinder. "Standard sliding force" refers to the sliding force (GF) measured under standard conditions. Similarly, "standard release force" refers to the release force (BLF) measured under standard conditions. Standard conditions include a standard stopper, i.e., a stopper with a hardness of 52 Shore A and a hardness of 1.355 g / cm, available from Datwyler Pharma Packaging International NV, Industrieterrein Kolmen 1519, BE-3570 Alken, Belgium. 3 The stoppers include Datwyler FM257 / 2 stoppers made of bromobutyl rubber with a density of 1000 psi. BLF and GF can be measured in one go. The test for BLF and GF is sometimes referred to as the "BLGF" test. Any reference to release force or slip force in this disclosure means standard release force or slip force.

[0127] The standard BLGF test is carried out in a universal testing machine at room temperature, i.e., 20°C. For this purpose, a standard BLGF test device with a 50N test cup is used. The sample is clamped vertically in a universal testing machine model 106 (2kN) manufactured by TesT AG, CH-6331 Hunenberg, Switzerland.

[0128] BLF is the force required to move the stopper from its original position. GF is the force required to continue moving the stopper after it is released.

[0129] The container is filled with water for injection. After filling with the sample, the sample is either stored or tested immediately, depending on the purpose of the test. The sample is tested without a needle attached.

[0130] The sample is inserted into the holder, and the pressure extruder is moved toward the stopper at a speed of 20 mm / min. When a force of 0.25 N is measured, the machine switches to a test speed of 100 mm / min and begins recording data. The experiment ends when the measured force exceeds 35 N, which is usually when the distal end of the hollow cylinder is reached.

[0131] The BLF is the highest force measured within the first 4 mm of stopper travel. The GF value is measured within the test range starting after 4 mm of travel and ending 10 mm before reaching the distal end of the hollow cylinder, and the GF according to the present disclosure is the highest sliding force measured in this experiment.

[0132] Containers of the present disclosure may exhibit a standard BLF of 12.0 N or less. In some embodiments, the standard BLF may be limited to an upper limit of 9.0 N, 8.0 N, 7.0 N, 6.0 N, 5.0 N, or even 4.0 N. The standard BLF may be at least 0.1 N, at least 0.5 N, or at least 1.0 N to avoid unintended movement of the stopper.

[0133] The container may exhibit a ratio of BLF / GF of standard BLF to standard GF greater than 1.30. Optionally, the ratio of standard BLF to standard GF is characterized by BLF / GF≦3.0. In embodiments, the ratio BLF / GF is greater than 1.40, greater than 1.50, or even greater than 1.60 for containers of the present disclosure. In some embodiments, the ratio BLF / GF may be less than 2.5, less than 2.2, less than 2.0, or even less than 1.9.

[0134] The standard GF of the containers of the present disclosure can be less than 7.5N, less than 6.5N, less than 5.5N, less than 4.5N, less than 3.5N, or even less than 2.5N.

[0135] Appropriate sliding and release forces are relevant to convenient use of the containers of the present disclosure. However, a sufficiently high release force may be beneficial to inhibit undesired stopper movement during storage. Optionally, the containers according to the present disclosure have a standard sliding force of at least 0.5 N.

[0136] To protect the seal by inhibiting stopper migration during cryogenic storage, the containers of the present disclosure can have a standard release force that exceeds the standard sliding force of the container by at least 30%, at least 60%, at least 100%, or at least 200%.

[0137] In one embodiment, the present disclosure relates to a container as described herein containing a pharmaceutical composition. The pharmaceutical composition may contain more than 60% water by weight. Optionally, the pharmaceutical composition contains a protein or nucleic acid therapeutic active agent.

[0138] Example Exemplary containers Referring now to the drawings, Figure 1 shows a container 1, in an exemplary embodiment, a syringe 3 for administering a pharmaceutical or cosmetic product. The syringe 3 is made of a polymer and includes a wall 5 surrounding a lumen. The container includes a hollow cylindrical body 7, an opening 4, and a nesting surface 18 onto which, for example, an injection needle or a cap can be placed. A stopper 12 is inserted into the cylindrical portion and is axially slidable by pressure from a push rod 13. The syringe 3 has a flange 15 for handling.

[0139] The container 1 is provided with a coating 10 on its inner surface, here specifically on the inner surface of the hollow cylinder 7. In this example, the coating 10 covers the area of ​​the inner surface of the hollow cylinder 7 over which the stopper 12 can slide when the syringe is being emptied or used to withdraw.

[0140] Coating Composition Two exemplary coating compositions useful in the methods of the present disclosure are shown in the table below. [Table 13]

[0141] Coating Thickness FIG. 2 illustrates the press-fit technique. An applicator 20 is inserted into a pharmaceutical container 1, here a syringe, having an opening 4 and a hollow cylindrical body 7. A coating composition 8 is applied to the applicator 20. The applicator 20 is in direct physical contact with the inner surface of the container. The coating composition 8 is deposited in a deposition area on the inner surface while the applicator 20 moves relative to the hollow cylindrical body 7, where the applicator moves downward, leaving a layer of coating composition 8 on the inner surface. When the applicator 20 reaches the opening 4 of the container 1, it is retracted from the container 1. A coated container 1 is obtained having a coating thickness distribution as shown in FIG. 4A.

[0142] 3A shows an applicator body 20 inserted into a hollow cylinder 7 having a wall 5 by press-fitting technique, while FIG. 3B shows an applicator body 20 inserted into a hollow cylinder 7 with a circumferential gap 22 between the applicator body 20 and the inner surface of the hollow cylinder 7. The applicator body 20 also comprises a duct 23 through which a coating composition can be applied to the applicator body such that it flows downwards towards the equator of the applicator body 20.

[0143] FIG. 5A shows an exemplary applicator body 20 having an equator 24 and a hemispherical shape for the portion of the applicator body 20 above the equator 24. k is the height of the capillary bridge on the surface of the coated body, and hw is the height of the capillary bridge on the inner surface of the hollow cylinder. Figure 5B shows a geometric diagram of a capillary bridge 25 that can be formed between the coated body 20 and the inner surface. D indicates the size of the gap spanned by the capillary bridge, R1 is the radius of curvature of the coated body, θ1 is the contact angle between the coating composition and the coated body, θ2 is the contact angle with the inner surface of the hollow cylinder, l is the azimuthal radius, and r is the meridional radius. β represents the position of the three-phase contact line on the particle surface. The height of the liquid meniscus is h.

[0144] A comparative experiment was conducted comparing the application of a coating by the press-fit technique with the application of another coating using the capillary bridge technique of the present disclosure, i.e., the same method as shown in Figure 2, but with a smaller diameter applicator body to allow for the formation of a capillary bridge. The coating composition and container were the same for both methods. For this experiment, a TopPac® 1 ml lg LL syringe was used. The syringe was made of COC with an inner surface having a surface energy of approximately 30 mN / m. The applicator body was a hemispherical PTFE head with a surface energy of approximately 18 mN / m. The coating composition had a surface energy of 13 mN / m and a viscosity of approximately 4 mPas. The syringe barrel had an inner diameter of 6.5 mm. The applicator body had an equatorial diameter of 6.4 mm.

[0145] Figure 4A shows a thickness analysis of a coating made according to the indentation method. Figure 4B shows a thickness analysis of a coating made according to the method of the present disclosure. The coating in Figure 4B is evidently very uniform, with an average thickness of 730 nm. The total area of ​​excess coating thickness was less than 5% of the coating area. The total area of ​​insufficient coating thickness (less than 100 nm) was less than 5% of the coating area.

[0146] The layer thickness distribution shown in Figure 4 was measured using a RapID Layer Explorer measuring device. The Layer Explorer RapID is a computer-aided device with an integrated interferometer. A camera for positioning is also connected. RapID allows for the measurement of the average film thickness inside transparent hollow cylinders, especially those based on glass and plastic. Other cylindrical primary packaging materials, such as cartridges, can also be measured.

[0147] Using the principle of white light reflectance measurement, the thickness of the coating is measured at multiple points (each 1 mm x 1 mm) on the coating, for example, at least 240 or 480 points distributed across the coating area. Measuring several points on the coating allows for quantitative determination of the coating distribution within the body. A related measurement mode is called BI mode (coating layer height > 100 nm). RapID can also be used to measure lower coating layer heights (> 20 nm). Measurements are performed using a laser as the light source. This measurement method is called UT mode (similar to ultrathin). The coating layer height is measured from 5 mm above the flange and at one point every millimeter up to the cone side. With these settings, there are 49 measurement points along the barrel. After measuring the entire length, the sample stage automatically rotates a predetermined angle and begins measuring a new line again. In this example, the sample stage rotation is always kept at 30°, which means 12 x 49 points = 588 points. Any image displayed is based on 588 single measurements. The RapID software represents the data as 2D false color and converts them into a 3D elevation or height profile. The coating thickness is represented by a gray scale (see Figure 4). Black indicates a layer thickness of 2000 nm, while white indicates 0 nm or no measurement. The RapID analyzer was used for layer thicknesses greater than 50 nm; layers less than 50 nm were counted as nonexistent. However, special settings on the RapID device allow for layer thicknesses as low as 20 nm to be measured.

Claims

1. 1. A method of making a coated container, comprising: providing a container including a hollow cylinder having a wall surrounding a lumen, said hollow cylinder having at least one opening; inserting an application body into the lumen through the opening; applying a coating composition to the application body such that the coating composition contacts at least a section of the inner surface of the wall; depositing the coating composition on a deposition area of ​​the inner surface of the wall by moving the applicator body relative to the hollow cylinder; retracting the applicator body from the lumen through the opening; Including, The method, wherein the application body is sized such that a circumferential gap exists between the application body and the inner surface of the wall during the depositing step.

2. The method of claim 1 , wherein the circumferential gap is sized such that the coating composition forms a capillary bridge spanning the circumferential gap during the depositing step.

3. 3. The method of claim 1, wherein the size of the circumferential gap is characterized by a distance D between the application body and the deposition area during the deposition step that is less than 0.10 mm.

4. The method of claim 3, wherein the distance D is 0.005 to 0.08 mm, or 0.01 to 0.04 mm.

5. The method according to at least one of claims 1 to 4, wherein the wall comprises or consists of a polymer material or glass.

6. 6. The method of claim 1, wherein the coating composition comprises, in weight percent: Table 1

7. 7. The method according to claim 1, wherein the speed of movement of the application body during deposition of the coating composition is less than or equal to the flow rate of the coating composition in the direction of movement of the application body.

8. air-flushing the container after depositing the coating composition on the deposition area; and / or curing the coating composition after depositing it on the deposition area to obtain a cured coating. The method according to claim 1 , further comprising:

9. the cylinder has a total internal diameter variation in the deposition region of up to 2D; and / or The application body has a total outer diameter variation of up to 2D; The method according to at least one of claims 3 to 8.

10. the application body comprises one or more ducts suitable for delivering the coating composition through the application body, and optionally the step of applying a coating composition to the application body comprises delivering the coating composition through the one or more ducts; and / or The step of applying a coating composition to the application body includes delivering the coating composition to a section above the equator of the application body and allowing the coating composition to flow downwardly on the application body; and / or the step of applying a coating composition to the application body includes delivering the coating composition to a section of the application body and allowing the coating composition to establish a capillary bridge between the application body and the inner surface of the wall. The method according to at least one of claims 1 to 9.

11. After hardening, the average coating thickness is between 100 and 3000 nm; and / or the total area of ​​excess coating thickness is less than 10% of the coating area, excess coating thickness being defined as an area exhibiting a coating thickness greater than two times the average coating thickness; The method according to at least one of claims 8 to 10.

12. The method according to at least one of claims 8 to 11, wherein after curing, the coating contains one or more silicon-organic polymers.

13. 13. A method according to claim 1, comprising a hollow cylinder having a wall surrounding a lumen, said hollow cylinder having at least one opening, and at least a part of the inner surface of said wall comprising a coating, the average coating thickness is 100-3000 nm, and the total area of ​​excess coating thickness is less than 10% of the coating area, excess coating thickness being defined as an area exhibiting a coating thickness greater than two times the average coating thickness; Coated container.

14. 14. The coated container of claim 13, wherein the coating comprises one or more silicon-organic polymers.

15. 15. The coated container of claim 13 or 14, wherein the total area of ​​insufficient coating thickness is less than 5% of the coating area, with insufficient coating thickness being defined as an area exhibiting a coating thickness of less than 100 nm.

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