Vessels, containers, and surfaces coated with water barrier coatings

Abstract

The container has an interior space defined at least in part by a wall. The wall has an inner surface facing the interior space, an outer surface, and plasma-enhanced chemical vapor deposition (PECVD) coatings supported by the wall. The PECVD coatings include a water barrier coating or layer having a water contact angle of 80 to 180 degrees and deposited using a precursor including at least one of a saturated or unsaturated fluorocarbon precursor having 1 to 6 carbon atoms and a saturated or unsaturated hydrocarbon having 1 to 6 carbon atoms. Optionally, the coatings include a SiOx gas barrier coating or layer having a thickness of 2 to 1000 nm, where x is 1.5 to 2.9 as measured using X-ray photoelectron spectroscopy (XPS), and optionally other related coatings.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Issued U.S. Patent No. 7,985,188, International Patent Application No. PCT / US2014 / 023813, filed March 11, 2014, International Patent Application No. PCT / US2016 / 047622, ​​filed August 18, 2016, and U.S. Provisional Patent Application No. 61 / 800,746, filed March 15, 2013, International Patent Application No. PCT / US2016 / 047622, ​​filed May 12, 2016. Nos. 62 / 335,506, 62 / 473,777, filed March 20, 2017, 62 / 648,778, filed March 27, 2018, 62 / 689,541, filed June 25, 2018, and 62 / 692,038, filed June 29, 2018, are incorporated herein by reference in their entirety. These patents / applications describe apparatus, precursors, coatings or layers, and methods (particularly coating methods and test methods for inspecting coatings or layers) that can be generally used in the practice of the present invention, unless otherwise noted herein. They also include the SiO 2 , SiO 3 , SiO 4 , SiO 5 , SiO 6 , SiO 7 , SiO 8 , SiO 9 , SiO 10 , SiO 11 , SiO 12 , SiO 13 , SiO 14 , SiO 15 , SiO 16 , SiO 17 , SiO 18 , SiO 29 , SiO 28 , SiO 29 , SiO 29 , SiO 39 , SiO 29 , SiO 29 , SiO 38 , SiO 29 , SiO 39 ... x Barrier coating or layer and SiO x C y Coatings are also described.

[0002] The present invention relates to the technical field of PECVD coated flat or non-flat surfaces with improved water barrier properties. More specifically, the present invention relates to surfaces coated with PECVD fluorocarbon or hydrocarbon or hydrofluorocarbon coatings with water barrier properties. The present invention also relates to containers having a water barrier coating on their interior and / or exterior surface or both surfaces.

[0003] The invention further relates to a method for producing the coated surface.The invention also relates to uses of the coated surfaces and containers. [Background technology]

[0004] One important consideration in the manufacture of sample containers for storing or otherwise contacting samples is that the contained sample have a substantial useful shelf-life. Often the sample or contents are subject to the effects of air, oxygen, moisture, or other environmental factors. During this useful shelf-life, it is important that the sample placed in the container is isolated from environmental gases such as oxygen and moisture. Thus, the barrier properties of the container are critical to the useful shelf-life of the contained sample.

[0005] Traditional glass pharmaceutical packages or other containers offer high barrier properties. However, they are prone to breakage or sample degradation during manufacturing, filling operations, shipping, and use, which means that glass particles can be introduced into the sample. Glass particle contamination is a frequent reason for FDA Warning Letters and product recalls.

[0006] As a result, some companies are moving to plastic pharmaceutical packages or other containers, which have greater dimensional tolerances and are less prone to breakage than glass. Several non-glass (e.g., plastic) prefilled syringes have been described. WO 2011 / 117878 A1 discloses a polycarbonate syringe. WO 2009 / 099641 A2 discloses a cyclic olefin polymer syringe. However, the use of plastics for primary pharmaceutical packaging is still limited by its gas permeability, i.e., plastics allow small molecules of gas, such as oxygen, and water molecules to pass into (or out of) the product. The gas permeability of plastics is much higher than that of glass. In many cases (such as oxygen-sensitive or moisture-sensitive drugs), the oxygen and water barrier properties of plastic containers need to be improved to be acceptable for pharmaceutical applications.

[0007] The permeability problem has been addressed by adding barrier coatings or layers to plastic pharmaceutical packages in locations that come into contact with the fluid contents of the package. One such barrier layer is SiO 2 deposited by plasma enhanced chemical vapor deposition, as defined below. x However, the unprotected SiO x The barrier layer can be etched by samples contained within the package, especially those with high pH values, thereby shortening the useful shelf life of the package by reducing its oxygen and water barrier efficiency.

[0008] Cyclic olefin copolymer / polymer (COC / COP) materials are relatively new thermoplastic materials that have many desirable properties. They are amorphous polyolefins and therefore transparent. They have low water absorption and high water barrier properties. In some cases, COP / COC may be good enough for storing solutions of drugs. In other cases, they do not provide the required water barrier properties. For example, some drugs that are hypersensitive to moisture are lyophilized for storage. Lyophilization is a freeze-drying process that removes water from a drug after freezing it and placing it under vacuum. During the shelf life of the lyophilized drug, the hypersensitive drug is stored in a container with a large vacuum headspace that facilitates oxygen / moisture penetration into the container. Therefore, containers for lyophilized drugs need to have extremely high oxygen and moisture barrier properties. COP / COC alone cannot provide the required oxygen / moisture barrier.

[0009] Teflon has been used as a water barrier material. However, there are problems with applying Teflon to pharmaceutical packages, containers, and containers. Teflon does not adhere well to the container walls and is not transparent enough.

[0010] definition In the context of the present invention, the following definitions and abbreviations are used:

[0011] RF is radio frequency.

[0012] The term "at least" in relation to the present invention means "equal to or more than" the integer following the term. The word "comprising" does not exclude other elements or steps, and the indefinite articles (a or an) do not exclude a plurality unless specifically indicated otherwise. Whenever a range for a parameter is given, it is intended to disclose values ​​for the parameter given as both ends of the range, and all values ​​of that parameter included within said range.

[0013] For example, references to a lubricant deposit, processing station, or processing device as "first" and "second" or the like refer to the minimum number of deposits, processing stations, or processing devices present, and do not necessarily represent the order or total number of deposits, processing stations, and devices, nor do they require additional deposits, processing stations, and devices beyond the number specified. These terms do not limit the number of processing stations or the specific processes performed at each station. For example, a "first" deposit in the context of this specification can be, and is not limited to, either the only deposit or any one of a number of deposits. In other words, a description of a "first" deposit may permit, but does not necessarily require, an embodiment having a second or subsequent deposit.

[0014] In the context of the present invention, an "induced silicon precursor" is a compound having at least one of the following chains: [ka] It is a tetravalent silicon atom linked to an oxygen or nitrogen atom and an organic carbon atom (an organic carbon atom is a carbon atom bonded to at least one hydrogen atom). Volatile organosilicon precursors, defined as precursors that can be delivered as a vapor to a PECVD apparatus, are optional organosilicon precursors. Optionally, the organosilicon precursor is selected from the group consisting of linear siloxanes, monocyclic siloxanes, polycyclic siloxanes, polysilsesquioxanes, alkyltrimethoxysilanes, linear silazanes, monocyclic silazanes, polycyclic silazanes, polysilsesquiazanes, and combinations of any two or more of these precursors.

[0015] The supply amounts of PECVD precursors, gaseous reactants or process gases, and carrier gases are sometimes expressed in the specification and claims as "standard volume". A standard volume of a charge or other fixed amount of gas is the volume that a fixed amount of gas occupies at standard temperature and pressure (without considering the actual supply temperature and pressure). Standard volume can be measured using different volume units and still be within the scope of this disclosure and claims. For example, the same fixed amount of gas can be expressed as the number of standard cubic centimeters, the number of standard cubic meters, or the number of standard cubic feet. Standard volume can also be defined using different standard temperatures and pressures and still be within the scope of this disclosure and claims. For example, the standard temperature could be 0° C. and the standard pressure could be 760 Torr (conventional), or the standard temperature could be 20° C. and the standard pressure could be 1 Torr. However, whatever standard conditions are used in each case, when comparing relative amounts of two or more different gases without specifying particular parameters, the same volume of each gas, standard temperature, and standard pressure will be used unless specifically indicated otherwise.

[0016] The corresponding delivery rates of PECVD precursors, gaseous reactants or process gases, and carrier gases are expressed herein in standard volume per unit time. For example, in the examples, delivery rates are expressed in standard cubic centimeters per minute, or sccm for short. As with other parameters, other units of time, such as seconds or hours, may be used, but consistent parameters shall be used when comparing flow rates of two or more gases unless otherwise indicated.

[0017] A "container" in the context of the present invention can be any type of container having at least one opening and a wall defining an interior or inner surface. The substrate can be a wall of a container having an interior space. The present invention is not necessarily limited to pharmaceutical packages or other containers of a particular volume, but pharmaceutical packages or other containers having an interior space with a void volume of 0.5-50 mL, optionally 1-10 mL, optionally 0.5-5 mL, optionally 1-3 mL are envisioned. The substrate surface can be part or all of the interior or inner surface of a container having at least one opening and an interior or inner surface. Some examples of pharmaceutical packages include, but are not limited to, vials, plastic-coated vials, syringes, plastic-coated syringes, blister packs, ampoules, plastic-coated ampoules, cartridges, bottles, plastic-coated pottles, pouches, pumps, sprayers, stoppers, needles, plungers, caps, stents, catheters, or implants.

[0018] The term "at least" in relation to the present invention means "equal to or more than" the integer following the term. Thus, a container in relation to the present invention has one or more openings. One or more openings are preferred, such as a sample tube (one opening) or a syringe barrel (two openings). If the container has two openings, these can be of the same or different size. If there are two or more openings, one opening can be used as a gas inlet for the PECVD coating method according to the present invention, and the other openings are capped or open. A container according to the present invention can be, for example, a sample tube for collecting or storing a biological fluid such as blood or urine, a syringe (or part thereof, for example a syringe barrel) for storing or delivering a biologically active compound or composition, such as a drug or pharmaceutical composition, a tube such as a catheter for transporting a biological material or a biologically active compound or composition, or a cuvette for holding a fluid, for example for holding a biological material or a biologically active compound or composition.

[0019] The container can be of any shape, with a container having a substantially cylindrical wall adjacent at least one of its open ends being preferred. Typically, the interior wall of the container is cylindrical, such as, for example, a sample tube or a syringe barrel. Sample tubes and syringes or portions thereof (e.g., syringe barrels) are envisioned.

[0020] By "hydrophobic layer" in the context of the present invention is meant a coating or layer that reduces the wetting tension of a surface covered with said coating or layer compared to a comparable surface without said coating. Hence, hydrophobicity is a function of both the uncoated substrate and the coating or layer. The same applies mutatis mutandis to other contexts in which the term "hydrophobic" is used. The term "hydrophilic" means the opposite, i.e., the wetting tension is increased compared to a reference sample. Hydrophobic layers in this application are essentially defined by their hydrophobicity and the process conditions that provide the hydrophobicity.

[0021] These values ​​of w, x, y, and z are applied throughout the specification to the experimental composition SiwOxCyHz. The values ​​of w, x, y, and z used throughout the specification should be understood as ratios or empirical formulas (e.g., of a coating or layer) and not as limitations on the number or type of atoms in the molecule. For example, octamethylcyclotetrasiloxane with molecular composition Si4O4C8H24 can be described by the following empirical formula obtained by dividing each of w, x, y, and z in the molecular formula by the greatest common factor of 4: SiO1C2H6. The values ​​of w, x, y, and z are also not limited to integers. For example, (acyclic) octamethyltrisiloxane with molecular composition Si3O2C8H24 can be converted to SiO0.67C2.67H8. Also, although SiOxCyHz is described as the equivalent of SiOxCy, it does not necessarily indicate the presence of hydrogen in any proportion to indicate the presence of SiOxCy.

[0022] The BIF is defined as the ratio of the uniform gas acceleration through an uncoated substrate to the uniform gas acceleration through a coated substrate. For example, the BIF for water vapor transmission through a coated container is the ratio WVTR(uncoated) / WVTR(coated).

[0023] By "water vapor barrier coating or layer (WVBC)" in this specification is meant a coating that reduces the water vapor transmission rate (WVTR) of a coated substrate compared to an uncoated substrate.

[0024] A "water vapor barrier coating or layer (WVBC)" may also be referred to as a "water barrier coating or layer (WBC)". In this specification, WVBC is interchangeable with WBC.

[0025] "Wetting tension" is a specific amount of hydrophobicity or hydrophilicity of a surface. The optional wetting tension measurement method for this invention is ASTM D 2578 or a modification of the method described in ASTM D 2578. This method uses standard wetting tension test liquids (called Dyne solutions) to identify the solution that comes closest to wetting the plastic film surface for exactly 2 seconds. This is the wetting tension of the film. The procedure used differs from ASTM D 2578 in that the substrate is not a flat plastic film, but a tube made according to the "Protocol for the formation of PET tubes" and coated according to the "Protocol for coating the inside of tubes with hydrophobic coatings or layers" (see Example 9 of EP 2251671 A2).

[0026] The atomic ratios can be determined by XPS. Thus, taking into account H atoms not measured by XPS, the coating or layer may have, for example, SiwOxCyHz (or equivalently, SiOxCy) in one embodiment, where w is 1, x is about 0.5 to about 2.4, y is about 0.6 to about 3, and z is about 2 to about 9. Typically, such coatings or layers thus contain 36% to 41% carbon, normalized to 100% carbon plus oxygen plus silicon.

[0027] The term "syringe" is broadly defined to include cartridges, injection "pens," and other types of barrels or containers that are adapted to be assembled with one or more other components to provide a functional syringe. "Syringe" is also broadly defined to include related products, such as autoinjectors, that provide a mechanism for expelling the contents.

[0028] "Triple coating or layer" refers to a group of coatings including a tie layer, a SiOx barrier coating, and a pH protective layer.

[0029] A coating or layer or treatment is defined as "hydrophobic" if it reduces the wetting tension of a surface compared to a comparable surface without the coating or treatment. Hydrophobicity is therefore a function of both the untreated substrate and the treatment.

[0030] The word "comprising" does not exclude other elements or steps.

[0031] The indefinite article (a or an) does not exclude a plurality. Summary of the Invention [Means for solving the problem]

[0032] An aspect of the invention is a container having an interior volume defined at least in part by a wall having an inner surface facing the interior volume, an outer surface, and a set of plasma enhanced chemical vapor deposition (PECVD) coatings supported by the wall, the PECVD coatings including a water barrier coating and a gas barrier coating.

[0033] The water barrier coating or layer has a water contact angle of 80-180 degrees. It is deposited using a water barrier coating or layer precursor that includes a saturated or unsaturated fluorocarbon precursor having 1-6 carbon atoms, a saturated or unsaturated hydrocarbon having 1-6 carbon atoms, or a saturated or unsaturated hydrofluorocarbon having 1-6 carbon atoms. Optionally, the precursor can include two or more of these precursors.

[0034] The gas barrier coating group consists of SiO x The container includes a gas barrier coating or layer, where x is 1.5 to 2.9 as measured by X-ray photoelectron spectroscopy (XPS). The gas barrier coating or layer has an inner surface facing the interior space and an outer surface facing the inner surface of the wall. The gas barrier coating or layer is effective for reducing ingress of atmospheric gases into the interior space, as compared to a container not having the gas barrier coating or layer.

[0035] Another aspect of the invention is a container having an interior volume defined at least in part by a wall having an inner surface facing the interior volume, an outer surface, and a plasma enhanced chemical vapor deposition (PECVD) coating carried by the wall, the PECVD coating including a water barrier coating.

[0036] The water barrier coating or layer has a water contact angle of 80-180 degrees. It is deposited using a water barrier coating or layer precursor that includes a saturated or unsaturated fluorocarbon precursor having 1-6 carbon atoms, a saturated or unsaturated hydrocarbon having 1-6 carbon atoms, or a saturated or unsaturated hydrofluorocarbon having 1-6 carbon atoms. Optionally, the precursor can include two or more of these precursors.

[0037] Yet another aspect of the invention is a method of manufacturing a container of any of the types described above. The method includes the steps of evacuating and dispensing. The evacuating step is carried out by at least partially evacuating an area adjacent to a surface of the wall to form a partially evacuated area. The water barrier precursor dispensing step is carried out by dispensing a precursor of a water barrier coating or layer into the partially evacuated area. A plasma is generated in the partially evacuated area to form a water barrier coating or layer supported by the wall adjacent the evacuated area.

[0038] Either before or after the step of supplying a precursor for the water barrier coating or layer, another step is to supply a precursor gas for a first coating or layer of the gas barrier coatings to the partially evacuated region and generate a plasma in the partially evacuated region to form one coating or layer of the gas barrier coatings supported by the wall adjacent the evacuated region.

[0039] Other aspects of the invention will become apparent from the following description and claims. [Brief description of the drawings]

[0040] [Figure 1] 1 is a schematic diagram of a coating system for applying a plasma enhanced chemical vapor deposition (PECVD) coating onto a container or other substrate. [Diagram 2] FIG. 1 is a schematic diagram of a PECVD coating vessel according to any embodiment of the present invention. [Figure 2A] FIG. 3 is an alternative detail view of the container of FIG. 2. [Figure 2B] FIG. 3 is another alternative detail view of the vessel of FIG. 2. [Diagram 3] FIG. 1 is a diagram of two different water droplet contact angles of water droplets on two different surfaces evaluated for contact angle. [Figure 4] 1 is a Fourier-Transform infrared spectrophotometry (FTIR) graph of transmittance versus wavenumber for polypropylene tubing with no coating, a PECVD coating with a C4H8 precursor, and a PECVD coating with a C3F6 precursor. [Diagram 5] FIG. 13 shows FTIR peak values ​​and assignments from 750 cm to 1800 cm for a PECVD water vapor barrier coating deposited on the inner surface of a 10 mL COP using a mixture of C4F8 precursor and Ar, with peak intensities shown in arbitrary absorptivity units. [Figure 6] 1 is a graph of data corresponding to Example 4 showing water vapor transmission rate values ​​for several different PECVD coated containers. [Figure 7] Schematic diagram of a typical atomic arrangement of silicon and oxygen expected in a SiOx PECVD coating, where x is approximately 2. [Figure 8] FIG. 8 is similar to FIG. 7 for a SiOxCyHz PECVD coating, where x is about 1, y is about 1, and z is about 3. [Figure 9] FIG. 8 is similar to FIG. 7 for a CFw coating with x about 1.5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0041] The following reference numbers are used in the present specification and drawings:

[0042] [Table 1]

[0043] With reference to the drawings, Figure 1 is a schematic diagram of a container coating machine 101 for processing containers such as those shown generally in Figures 2, 2A, and 2B. The coating machine 101 may be used to apply PECVD coatings, such as those shown generally in Figures 7, 8, and 9. The PECVD coating apparatus and process may also be as generally described in the PECVD protocols of U.S. Patent No. 7,985,188, International Patent Application No. PCT / US2014 / 023813, or International Patent Application No. PCT / US2016 / 047622. The entire text and drawings of U.S. Patent No. 7,985,188, International Patent Application No. PCT / US2014 / 023813, or International Patent Application No. PCT / US2016 / 047622 are incorporated herein by reference.

[0044] The container coater 101 includes gas sources such as 103, 105, 107, and 109 for any process gases that are used, which may be, for example, precursor, reactant, or carrier gases. The representation of specific gases in Figure 1 is representative, i.e., not all of these specific gases must be present, and other gases not specifically shown may be used. Typically, each gas source has a meter such as 111, 113, 115, and 117 to control the amount of each gas that will be used for PECVD.

[0045] The gases used are mixed in the gas mixing chamber 119 and then delivered into the reaction chamber via the reaction chamber inlet valve 121. If the outside of the vessel is to be coated, the reaction chamber 123 can be a separate chamber in which the workpiece to be coated is placed. If the inside of the vessel is to be coated, the reaction chamber 123 can be the interior space of the vessel to be coated, with gas inlets and gas outlets to deliver gases into and out of the interior space. A representative apparatus for coating the interior surface of a vessel is described, for example, in U.S. Pat. No. 7,985,188, e.g., in FIG. 2 of that patent and the associated description. The reaction chamber can be provided with a pressure control device 125 for maintaining the reaction pressure used for PECVD.

[0046] In the reaction chamber 123, exhaust gas is generated as a result of the coating process. The exhaust gas is exhausted from the reaction chamber 123 via the reactor outlet valve 127. Optionally, if one or more components of the exhaust gas are to be collected, the vacuum line valve 129 is closed and the cold trap valve 131 is opened. This diverts the exhaust gas to a cold trap 133 or other collection device for collecting one or more components of the exhaust gas, and then any components leaving the cold trap 133 are sent through the vacuum pump 135 to the exhaust 137. Alternatively, if the exhaust gas is sent directly through the vacuum pump 135 and no diversion and collection of the exhaust gas components is performed, the cold trap valve 131 can be closed and the vacuum line valve 129 can be opened to allow the exhaust gas to be sent directly from the reaction chamber 123 through the vacuum pump 135 and then to the exhaust 137.

[0047] PECVD requires an energy source to generate the plasma, which in the illustrated apparatus is provided by an electromagnetic energy source 139. As shown, the energy source 139 is a radio frequency generator that generates RF energy at a frequency approved for PECVD, e.g., 13.56 MHz. The energy source 139 can also, or instead, be a microwave generator, where the microwave energy is conventionally guided to the reaction chamber 123 by a waveguide. Energy from the energy source 139 is conveyed into the reaction chamber 123, in this embodiment, through an electrode 141, to a suitable applicator within or forming the wall of the reaction chamber 143. Alternatively, as shown in U.S. Pat. No. 7,985,188, e.g., FIG. 2, a grounded hollow inner electrode is a hollow tube that conveys process gases into the reaction chamber 123, and a conducting electrode is connected to an external applicator that surrounds or is adjacent to the reaction chamber 123.

[0048] Many different types of apparatus for performing PECVD are known to those skilled in the art, and the present disclosure is not limited to any particular apparatus or method unless expressly indicated otherwise within a particular embodiment herein.

[0049] 2, 2A, and 2B, a PECVD coating vessel 210 is shown having an interior space 212 defined at least in part by a wall 214. The wall 214 has an inner surface 278 facing the interior space 212, an outer surface 216, and a plasma enhanced chemical vapor deposition (PECVD) coating 302 supported by the wall 214. Optionally, the vessel 210 may have an opening and closing means, shown diagrammatically as 262 in FIG. The opening and closing means 262 may optionally include one or more coatings, such as a coating 285, which may be any of the coatings provided herein or individual coatings.

[0050] The PECVD coating group 302 includes water barrier coatings or layers 300 having water contact angles between 80 and 180 degrees, optionally between greater than 80 and less than 180 degrees, optionally between 90 and 160 degrees, optionally between 100 and 150 degrees, optionally between 110 and 150 degrees. The water barrier coatings or layers 300 can be deposited using a water barrier coating or layer 300 precursor that includes at least one of a saturated or unsaturated fluorocarbon precursor having 1 to 6 carbon atoms, a saturated or unsaturated hydrocarbon having 1 to 6 carbon atoms, and a saturated or unsaturated hydrofluorocarbon having 1 to 6 carbon atoms.

[0051] Gas barrier coating group 298 optionally includes a SiOx gas barrier coating or layer 288 having a thickness of 2-1000 nm, where x is 1.5-2.9 as measured using an X-ray photoelectron spectroscopy (XPS), the gas barrier coating or layer 288 having an inner surface 220 facing the interior space 212 and an outer surface 222 facing the interior surface 278 of the wall 214, the gas barrier coating or layer 288 being effective in reducing the ingress of atmospheric gases into the interior space 212 as compared to the container 210 not having the gas barrier coating or layer 288.

[0052] Optionally, in any embodiment, the individual coatings and layers can be in various orders. For example, as shown in FIG. 2B, a water barrier coating or layer 300 can be positioned between the gas barrier coating group 298 and the inner surface 278 of the wall 214.

[0053] Optionally, in any embodiment, the gas barrier coatings 298 are measured using an X-ray photoelectron spectrometer (XPS) that does not measure hydrogen that may be present. x C y or SiN x C ywhere x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3 as measured using XPS. pH protective coating or layer 286 optionally has an inner surface 224 facing interior space 212 and optionally an outer surface 226 facing inner surface 220 of gas barrier coating or layer 288.

[0054] Optionally, in any embodiment, gas barrier coating group 298 further includes a bond coating or layer 289 comprising SiOxCy or SiNxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3 as measured using XPS. Optionally, in any embodiment, bond coating or layer 289 can have an inner surface 291 facing the gas barrier coating or layer 288 and an outer surface 293 facing the water barrier coating or layer 300.

[0055] Optionally, in some embodiments, the bonding coating or layer 289 is in direct contact with the wall 214, the barrier coating or layer 288 is between the bonding coating or layer 289 and the pH protective coating or layer 286, and the water barrier coating or layer 300 is deposited on the inner surface 224 of the pH protective coating or layer 286.

[0056] Optionally, in some embodiments, the water vapor transmission rate (WVTR) of the container 210 is lower than that of a comparable container 210 without the gas barrier coatings 298 .

[0057] Optionally, in any embodiment, the water vapor transmission rate (WVTR) of the container 210 is lower than a comparable container 210 without the water barrier coating or layer 300 .

[0058] Optionally, in either embodiment, the water contact angle of the coating surface is greater than that of the same container 210 having only the water barrier coating or layer 300 or only the gas barrier coating group 298 .

[0059] Optionally, in either embodiment, the water barrier coating 300 is deposited directly on the wall 214 and a gas barrier coating group 298 is deposited on top of the water barrier coating 300, the gas barrier coating group 298 including a SiOx gas barrier coating or layer 288, a pH protective coating or layer 286, and a bond coating or layer 289, the bond coating or layer 289 being in direct contact with the water barrier coating 300 and the barrier coating or layer 288 being between the bond coating or layer 289 and the pH protective coating or layer 286.

[0060] Optionally, in either embodiment, a water barrier coating or layer 300 is on the exterior surface 216 of the vessel wall 214 and a gas barrier coating group 298 is on the interior surface 278 of the vessel wall 214 .

[0061] Optionally, in any embodiment, the plasma enhanced chemical vapor deposition (PECVD) coating group 302 includes a water barrier coating or layer 300 having a water contact angle between 80 and 180 degrees, optionally between greater than 80 and less than 180 degrees, optionally between 90 and 160 degrees, optionally between 100 and 150 degrees, optionally between 110 and 150 degrees.

[0062] container The container may be embodied in various forms and should not be construed as being limited to the embodiments set forth herein, but rather, these embodiments are examples of the invention having the fullest scope indicated by the language of the claims.

[0063] Optionally, in any embodiment, the container 210 can be, for example, a microplate, a centrifuge tube, a well plate, a microwell plate, a vial, a pipette, a bottle, a jar, a syringe, a cartridge, a flask, a cryovial, a blister package, an ampoule, a vacutainer, a specimen tube, a chromatography vial, a cosmetic container, a medical diagnostic straw, a sample vial, an assay tube, a transfer pipette, a reagent container, rigid or flexible tubing, a Cobas® Liat® System container 210, or any container 210 defined herein or in any other claim. Optionally, in any embodiment, the container 210 can have a generally cylindrical interior space 212. Optionally, in any embodiment, the interior space 212 has an inner diameter, an inner axial length, and a ratio of 1:1 to 20:1, optionally 1:1 to 15:1, optionally 1:1 to 10:1, optionally 1:1 to 5:1, optionally 1:1 to 3:1, optionally 1:1 to 2:1, optionally 2:1 to 20:1, optionally 2:1 to 15:1, optionally 2:1 to 10:1, optionally 2:1 to 5:1, optionally It may have an internal axial length to internal diameter aspect ratio of 2:1 to 3:1, optionally 3:1 to 20:1, optionally 3:1 to 15:1, optionally 3:1 to 10:1, optionally 3:1 to 5:1, optionally 5:1 to 20:1, optionally 5:1 to 15:1, optionally 5:1 to 10:1, optionally 10:1 to 20:1, optionally 10:1 to 15:1, optionally 15:1 to 20:1.

[0064] Optionally, in any embodiment, at least a portion of the wall 214 comprises an olefin polymer, polypropylene (PP), polyethylene (PE), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polymethylpentene, polystyrene, hydrogenated polystyrene, polycyclohexylethylene (PCHE), heteroatom-substituted hydrocarbon polymer, polyester, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polybutylene terephthalate (PBT), polyvinylidene chloride (PVdC), polyvinyl chloride (PVC), polycarbonate, polylactic acid, epoxy resin, nylon, polyurethane polyacrylonitrile, polyacrylonitrile (PAN), ionomer resin, Surlyn® ionomer resin, or any combination, composition, or blend of any two or more of the above materials, optionally including PET, COP, or PP, and optionally including COP.

[0065] In at least one embodiment, the container wall is made of a thermoplastic polymeric material, such as polyester, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyolefin, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polypropylene (PP), or polycarbonate. The wall may be made of multiple layers of cyclic olefin polymer (COP) or cyclic olefin copolymer (COC) resins with other resins sandwiched therebetween. The sandwiched resins may include EVOH, EVA, PET, nylon, or saran, or any combination thereof. Optionally, in any embodiment, the wall 214 includes polyethylene terephthalate (PET) and a water barrier coating 300 supported by the wall 214.

[0066] Optionally, in any embodiment, container 210 may contain moisture sensitive materials, optionally lyophilized drugs, diagnostic reagents, or topical tissue adhesives.

[0067] Optionally, in either embodiment, the exterior surface 216 of the vessel wall 214 does not have a PECVD coating. Alternatively, an exterior coating group 301 can be provided, which can include any or all of the interior layers, and optionally can be a water barrier coating or layer, as shown, provided in conjunction with or in place of the interior water barrier coating or layer 300 shown in Figures 2A and 2B.

[0068] Water barrier coating or layer Optionally, in any embodiment, the water barrier coating or layer 300 is between 1 nm and 500 nm thick, alternatively between 1 nm and 400 nm thick, alternatively between 1 nm and 300 nm thick, alternatively between 1 nm and 200 nm thick, alternatively between 1 nm and 100 nm thick, alternatively between 1 nm and 80 nm thick, alternatively between 1 nm and 60 nm thick, alternatively between 1 nm and 50 nm thick, alternatively between 1 nm and 40 nm thick, alternatively between 1 nm and 30 nm thick, alternatively between 1 nm and 20 nm thick, alternatively between 1 nm and 10 nm thick, alternatively between 1 nm and 5 nm thick, alternatively between 10 nm and 500 nm thick, alternatively between 10 nm and 400 nm thick, alternatively between 10 nm and 300 nm thick, alternatively between 10 nm and 200 nm thick, alternatively between 10 nm and 100 nm thick. , alternatively 10nm to 80nm thick, alternatively 10nm to 60nm thick, alternatively 10nm to 50nm thick, alternatively 10nm to 40nm thick, alternatively 10nm to 30nm thick, alternatively 10nm to 20nm thick, alternatively 1nm to 10nm thick, alternatively 1nm to 5nm thick, alternatively 50nm to 500nm thick, alternatively 50nm to 400nm thick, alternatively 50nm to 300nm thick, alternatively 50nm to 200nm thick, alternatively 50nm to 100nm thick, alternatively 50nm to 80nm thick, alternatively 50nm to 60nm thick, alternatively 100nm to 500nm thick, alternatively 100nm to 400nm thick, alternatively 100nm to 300nm thick, alternatively 100nm to 200nm thick.

[0069] Optionally, in either embodiment, the water barrier coating or layer 300 is in direct contact with the wall 214 .

[0070] Optionally, in either embodiment, the water barrier coating or layer 300 is in direct contact with the inner surface 278 of the wall 214 .

[0071] Optionally, in either embodiment, the water barrier coating or layer 300 is in direct contact with the exterior surface 216 of the wall 214 .

[0072] Optionally, in either embodiment, a water barrier coating or layer 300 is in direct contact with the exterior surface 216 of the wall 214 and another, the same or different, water barrier coating or layer 300 is in direct contact with the interior surface of the wall 214 .

[0073] Optionally, in any embodiment, the container 210 including the water barrier coating or layer 300 has a water vapor transmission barrier improvement factor (BIF) greater than 1, optionally between 2 and 8, optionally between 4 and 8, and optionally between 6 and 8, compared to a comparable container 210 without the water barrier coating or layer 300.

[0074] Optionally, in any embodiment, the water vapor transmission rate (WVTR) of the container 210 is lower than that of a comparable container 210 without the water barrier coating or layer 300 .

[0075] Optionally, in any embodiment, the water vapor transmission barrier improvement factor (BIF) for at least one of water, dimethyl sulfoxide (DMSO), ethanol, or any combination of two or more thereof, compared to a comparable container 210 without the water barrier coating or layer 300 is greater than 1, optionally between 2 and 20, optionally between 4 and 20, optionally between 6 and 20, optionally between 8 and 20, optionally between 2 and 10, optionally between 4 and 10, optionally between 6 and 10, optionally between 8 and 10, optionally between 2 and 5, optionally between 4 and 5, optionally between 1.5 and 10, optionally between 1.5 and 8, optionally between 1.5 and 6, optionally between 1.5 and 4, optionally between 1.5 and 2.

[0076] The water barrier coating or layer of the present invention is deposited by PECVD using a coating machine, which may be the coating machine described above with respect to FIG.

[0077] The coating precursor includes a fluorocarbon, a hydrocarbon, or a hydrofluorocarbon. The fluorocarbon can be a fluorinated compound, for example, a saturated or unsaturated linear or cyclic aliphatic fluorocarbon precursor having 1-10, optionally 1-6, optionally 2-6 carbon atoms and 4-20 fluorine atoms per molecule. Some specific examples of suitable fluorinated compounds include fluorinated gases, such as hexafluoropropylene (C3F6), octafluorocyclobutane (C4F8), tetrafluoroethylene (C2F4), or hexafluoroethane (C2F6), optionally hexafluoropropylene (C3F6) or octafluorocyclobutane (C4F8), or fluorinated liquids, such as perfluoro-2-methyl-2-pentene (C6F12) or perfluorohexane (C6F14), or any combination thereof. The hydrocarbons can be lower alkanes having 1-4 carbon atoms, alkenes or alkynes having 2-4 carbon atoms, such as acetylene (C2H2) or methane (CH4), optionally acetylene (C2H2).The hydrofluorocarbons can be saturated or unsaturated, have 1-6 carbon atoms, at least one hydrogen atom, and at least one fluorine atom per molecule, or any combination, composition, or blend of any two or more of the above materials.

[0078] The water barrier coating or layer of the present invention is deposited by PECVD using a coating machine, which may optionally be the coating machine described above in connection with FIG.

[0079] For water barrier coatings deposited using fluorocarbons as precursors, typical coating process conditions are as follows: Power supply frequency: 13.56MHz Precursor: Hexafluoropropylene (C3F6) or Octafluorocyclobutane (C4F8) Gas flow rate: 5 to 10 sccm ○ Carrier gas flow rate: 2~10sccm Base pressure: 20 to 300 mTorr Coating pressure: 80-900mTorr Coating time: 5 to 30 seconds

[0080] For water barrier coatings deposited using hydrocarbons as precursors, typical coating process conditions are as follows: Power supply frequency: 13.56MHz Precursor: Acetylene (C2H2) Gas flow rate: 1 to 10 sccm ○ Carrier gas flow rate: 2~5sccm Base pressure: 20 to 300 mTorr Coating pressure: 80-900mTorr Coating time: 5 to 30 seconds

[0081] Optionally, the inlet can be stationary or movable during the process.

[0082] The water barrier coating can be characterized by FT-IR, water contact angle, and XPS.

[0083] Bonding Coating or Layer The tie coating or layer 289 has at least two functions. One function of the tie coating or layer 289 is to improve the adhesion of the barrier coating or layer 288 to a substrate, particularly a thermoplastic substrate, although the tie layer can be used to improve adhesion to a glass substrate or other coating or layer. For example, a tie coating or layer, also called an adhesion layer or coating, can be deposited on a substrate and a barrier layer can be deposited on the adhesion layer to improve the adhesion of the barrier layer or coating to the substrate.

[0084] Other functions of the tie coating or layer 289 have been discovered, namely, that the tie coating or layer 289 deposited under the barrier coating or layer 288 can improve the function of the pH protective coating or layer 286 deposited on the barrier coating or layer 288.

[0085] The bond coating or layer 289 can be composed of, comprised of, or consist essentially of SiOxCy, where x is between 0.5 and 2.4, and y is between 0.6 and 3. Alternatively, the atomic ratios can be expressed as the chemical formula SiwOxCy. The atomic ratios of Si, O, and C in the bond coating or layer 289 are as follows, as some options: Si 100:O 50-150:C 90-200 (i.e., w=1, x=0.5-1.5, y=0.9-2), Si 100:O 70-130:C 90-200 (i.e., w=1, x=0.7-1.3, y=0.9-2), Si 100:O 80-120:C 90-150 (i.e., w=1, x=0.8-1.2, y=0.9-1.5), Si 100:O 90-120:C 90-140 (i.e., w=1, x=0.9-1.2, y=0.9-1.4), or Si 100:O 92-107:C 116-133 (i.e., w=1, x=0.92-1.07, y=1.16-1.33),

[0086] The atomic ratios can be determined by XPS. Thus, taking into account H atoms not measured by XPS, the bond coating or layer 289 in one embodiment may have the formula SiwOxCyHz (or its equivalent SiOxCy), where w is 1, x is about 0.5 to about 2.4, y is about 0.6 to about 3, and z is about 2 to about 9. Typically, the bond coating or layer 289 thus contains 36% to 41% carbon normalized to 100% carbon plus oxygen plus silicon.

[0087] Optionally, the tie coating or layer can be similar or the same in composition as the pH protective coating or layer 286 described elsewhere herein, although this is not a requirement.

[0088] Bond coating or layer 289, in any embodiment, is contemplated to be generally between 5 nm and 100 nm thick, preferably between 5 and 20 nm thick, particularly when deposited by chemical vapor deposition. These thicknesses are not critical. Typically, but not necessarily, bond coating or layer 289 is relatively thin, since its function is to modify the surface properties of the substrate.

[0089] Barrier Layer A barrier coating or layer 288 can optionally be deposited by plasma enhanced chemical vapor deposition (PECVD) or other chemical vapor deposition process on the container of a pharmaceutical package, particularly a thermoplastic package, to prevent oxygen, carbon dioxide, or other gases from entering the container and / or to prevent leaching of pharmaceutical materials into or through the wall of the package.

[0090] The barrier coating or layer for any embodiment defined herein (unless otherwise specified in a particular example) is optionally a coating or layer deposited by PECVD as described in U.S. Pat. No. 7,985,188, International Patent Application No. PCT / US2014 / 023813, or International Patent Application No. PCT / US16 / 47622. The barrier layer may optionally be characterized as a "SiOx" coating, comprising silicon, oxygen, and optionally other elements, where x, i.e., the ratio of oxygen atoms to silicon atoms, is about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. These alternative definitions of x apply to any use of the term SiOx herein. The barrier coating or layer is deposited, for example, on the interior of a pharmaceutical package or other container, such as a cell culture flask, a cell culture Erlenmeyer flask, a cell culture vessel, a roller bottle, a ribbed roller bottle, a sample collection tube, a syringe barrel, a vial, or other type of container.

[0091] The barrier coating 288 comprises or consists essentially of SiOx, where x is between 1.5 and 2.9, has a thickness between 2 and 1000 nm, the SiOx barrier coating 288 having an inner surface facing the interior space 212 and an outer surface 222 facing the wall 214 product surface 254, and the barrier coating 288 is effective in reducing the ingress of atmospheric gases into the interior space 212 as compared to an uncoated container 250. One suitable barrier composition, for example, is one where x is 2.3. For example, a barrier coating or layer such as 288 in any embodiment can be deposited to a thickness of at least 2 nm, or at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm. The barrier coating or layer may be up to 1000 nm, or up to 900 nm, or up to 800 nm, or up to 700 nm, or up to 600 nm, or up to 500 nm, or up to 400 nm, or up to 300 nm, or up to 200 nm, or up to 100 nm, or up to 90 nm, or up to 80 nm, or up to 70 nm, or up to 60 nm, or up to 50 nm, or up to 40 nm, or up to 30 nm, or up to 20 nm, or up to 10 nm, or up to 5 nm thick. Ranges of 20-200 nm, optionally 20-30 nm, are contemplated. Specific thickness ranges consisting of any one of the minimum thicknesses listed above plus one or more of the maximum thicknesses listed above are expressly contemplated.

[0092] The thickness of the SiOx or other barrier coating or layer can be measured, for example, by transmission electron microscopy (TEM) and its composition can be measured by X-ray photoelectron spectroscopy (XPS). The primer coatings or layers described herein can be deposited on a variety of pharmaceutical packages or other containers, for example made of plastic or glass, such as plastic tubes, vials, and syringes.

[0093] A barrier coating or layer 288 of SiOx, where x is between 1.5 and 2.9, is deposited by plasma enhanced chemical vapor deposition (PECVD) directly or indirectly (e.g., a tie coating or layer 289 can be interposed therebetween) on the thermoplastic wall 214 such that in the filled pharmaceutical package or other container 210, the barrier coating or layer 288 is positioned between the interior or inner surface of the thermoplastic wall 214 and the fluid contained within the interior space.

[0094] A barrier coating or layer 288 of SiOx is supported by the thermoplastic wall 214. The barrier coating or layer 288 described elsewhere herein or in U.S. Pat. No. 7,985,188, International Patent Application No. PCT / US2014 / 023813, or International Patent Application No. PCT / US16 / 47622 may be used in any of the embodiments.

[0095] It has been found that certain barrier coatings or layers 288, such as SiOx as defined herein, are characterized by a measurable decrease in the barrier improvement factor in less than six months as a result of attack by the relatively high pH contents of the coating container as described elsewhere herein, particularly when the barrier coating or layer is in direct contact with the contents. This problem can be addressed using the pH protective coatings or layers discussed herein.

[0096] The SiOx barrier coating or layer 288 can also function as a primer coating or layer, as discussed elsewhere herein.

[0097] pH protective coating or layer The inventors have discovered that SiOx barrier layers or coatings are corroded or dissolved by certain fluids, for example aqueous compositions with a pH greater than about 5. Because coatings deposited by vapor-phase chemical deposition are very thin, and can be tens to hundreds of nanometers thick, even relatively slow corrosion can cause the effectiveness of the barrier layer to disappear or become less effective before the desired useful shelf life of the product package. This is particularly problematic for fluid pharmaceutical compositions, many of which have a pH in the range of approximately 7, or more broadly 5 to 9, similar to the pH of blood and other human or animal bodily fluids. The higher the pH of the pharmaceutical preparation, the more rapidly it corrodes or dissolves the SiOx coating. Optionally, this problem can be addressed by protecting the barrier coating or layer 288, or other pH-sensitive materials, with a pH protective coating or layer 286.

[0098] Optionally, the pH protective coating or layer 286 can be composed of, comprised of, or consist essentially of SiwOxCyHz (or equivalently SiOxCy) or SiwNxCyHz or equivalently Si(NH)xCy), respectively, as defined above. The atomic ratio of Si:O:C or Si:N:C can be determined by XPS (X-ray Photoelectron Spectroscopy). Thus, taking into account H atoms, the pH protective coating or layer, in one embodiment, can have a chemical formula of SiwOxCyHz, e.g., equivalently SiOxCy, where x is 1, x is about 0.5 to about 2.4, y is about to about 3, and z is about 2 to about 9.

[0099] Typically expressed as the chemical formula SiwOxCy, the atomic ratios of Si, O, and C are as follows, with some options: Si 100:O 50-150:C 90-200 (i.e. w=1, x=0.5-1.5, y=0.9-2), Si 100:O 70-130:C 90-200 (i.e. w=1, x=0.7-1.3, y=0.9-2), Si 100:O 80-120:C 90-150 (i.e. w=1, x=0.8-1.2, y=0.9-1.5), Si 100:O 90-120:C 90-140 (i.e. w=1, x=0.9-1.2, y=0.9-1.4), Si 100:O 92-107:C 116-133 (i.e. w=1, x=0.92-1.07, y=1.16-1.33), or Si 100: 80~130:C 90~150

[0100] Alternatively, the pH protective coating or layer can have an atomic concentration of less than 50% carbon and greater than 25% silicon normalized to 100% carbon, oxygen, and silicon as determined by X-ray photoelectron spectroscopy (XPS). Alternatively, the atomic concentrations are 25-45% carbon, 25-65% silicon, and 10-35% oxygen.

[0101] Alternatively, the atomic concentrations are 30-40% carbon, 32-52% silicon, and 20-27% oxygen.Alternatively, the atomic concentrations are 33-37% carbon, 37-47% silicon, and 22-26% oxygen.

[0102] The thickness of the pH protective coating or layer can be, for example: 10nm~1000nm, Alternatively, 10nm to 1000nm; Alternatively, 10nm to 900nm; Alternatively 10nm to 800nm, Alternatively, 10nm to 700nm; Alternatively, 10nm to 600nm; Alternatively, 10nm to 500nm; Alternatively, 10nm to 400nm; Alternatively, 10nm to 300nm; Alternatively, 10nm to 200nm; Alternatively, 10nm to 100nm; Alternatively, 10nm to 50nm; Alternatively, 20nm to 1000nm; Alternatively, 50nm to 1000nm; Alternatively, 10nm to 1000nm; Alternatively 50nm to 800nm, Alternatively, 100nm to 700nm; Alternatively 300nm~600nm.

[0103] Optionally, the protective layer can have an atomic concentration of carbon, normalized to 100% carbon, oxygen, and silicon, as determined using X-ray photoelectron spectroscopy (XPS), greater than the atomic concentration of carbon in the atomic formula of the organosilicon precursor. For example, embodiments are contemplated in which the atomic concentration of carbon is increased by 1 to 80 atomic percent, alternatively 10 to 70 atomic percent, alternatively 20 to 60 atomic percent, alternatively 30 to 50 atomic percent, alternatively 35 to 45 atomic percent, or alternatively 37 to 41 atomic percent.

[0104] Optionally, the carbon to oxygen atomic ratio of the pH protective coating or layer can be increased compared to the organosilicon precursor, and / or the oxygen to silicon atomic ratio can be decreased compared to the organosilicon precursor.

[0105] Optionally, the atomic concentration of silicon in the pH protective coating or layer, as characterized using X-ray photoelectron spectroscopy (XPS), normalized to 100% carbon, oxygen, and silicon, can be lower than the atomic concentration of silicon in the atomic formula for the feed gas. For example, embodiments are contemplated in which the atomic concentration of silicon is reduced by 1 to 80 atomic percent, alternatively 10 to 70 atomic percent, alternatively 20 to 60 atomic percent, alternatively 30 to 55 atomic percent, alternatively 40 to 50 atomic percent, or alternatively 42 to 46 atomic percent.

[0106] Alternatively, in any embodiment, a pH protective coating or layer is contemplated that is characterized by a sum formula that can increase the atomic ratio C:O and / or decrease the atomic ratio Si:O as compared to the sum formula of the organosilicon precursor.

[0107] The pH protective coating or layer 286 is generally positioned between the barrier coating or layer 288 and the fluid in the finished product. The pH protective coating or layer 286 is supported by the thermoplastic wall 214.

[0108] The pH protective coating or layer 286 is optionally effective in keeping the barrier coating or layer 288 at least substantially undissolved as a result of attack by the fluid 218 for at least six months.

[0109] The concentration of the pH protective coating or layer can be 1.25-1.65 g / cm3, alternatively 1.35-1.55 g / cm3, alternatively 1.4-1.5 g / cm3, alternatively 1.4-1.5 g / cm3, alternatively 1.44-1.48 g / cm3, as determined using X-ray reflectometry (XRR). Optionally, the organosilicon compound can be octamethylcyclotetrasiloxane, and the pH protective coating or layer can have a concentration that can be higher than that of a pH protective coating or layer fabricated from HMDSO as the organosilicon compound under the same PECVD reaction conditions.

[0110] The pH protective coating or layer may optionally prevent or reduce precipitation of compounds or components of a composition in contact with the pH protective coating or layer, and in particular may prevent or reduce insulin precipitation or blood clotting, as compared to uncoated surfaces and / or barrier coated surfaces using HMDSO as a precursor.

[0111] The pH protective coating or layer can optionally have an RMS surface roughness value (as measured by AFM) of from about 5 to about 9, optionally from about 6 to about 8, optionally from about 6.4 to about 7.8. The pH protective coating or layer can have an Ra surface roughness value as measured by AFM of from about 4 to about 6, optionally from about 4.6 to about 5.8. The pH protective coating or layer can have an Rmax surface roughness value as measured by AFM of from about 70 to about 160, optionally from about 84 to about 142, optionally from about 90 to about 130.

[0112] The contact angle (with distilled water) of the pH protected inner surface can optionally be between 90° and 110°, optionally between 80° and 120°, optionally between 70° and 130°, as measured using goniometer goniometer measurements of a water drop on the pH protected surface according to ASTM D7334-08 “Standard Practice for Surface Wettability of Coatings, Substrates and Pigments by Advancing Contact Angle Measurement”.

[0113] The passivation layer or pH protective coating or layer 286 optionally exhibits an O parameter measured at attenuated total reflectance (ATR) of less than 0.4, measured as follows:

number

[0114] The O parameter is defined in U.S. Patent No. 8,067,070, which claims a wide range of O parameter values ​​from 0.4 to 0.9. This can be measured from physical analysis of a graph of FTIR amplitude versus wavenumber to obtain the numerator and denominator of the above expression, as shown in FIG. 6, which is the same as FIG. 5 of U.S. Patent No. 8,067,070, except that it is annotated to show the interpolation of the wavenumber and absorbance scales to arrive at an absorbance of 0.0424 at 1253 cm-1 and a maximum absorbance of 0.08 between 1000 and 1100 cm-1, resulting in an O parameter of 0.53. The O parameter can also be measured from digital wavenumber versus absorbance data.

[0115] US Patent No. 8,067,070 asserts that the claimed range of O parameters provides superior pH protective coatings or layers based on experiments using only HMDSO and HMDSN, both of which are non-cyclic siloxanes. Surprisingly, the inventors have found that when the PECVD precursor is a cyclic siloxane, such as OMCTS, O parameters outside the range claimed in US Patent No. 8,067,070 provide much better results with the use of OMCTS than those obtained with HMDSO in US Patent No. 8,067,070.

[0116] Alternatively, in this embodiment, the value of the O parameter is between 0.1 and 0.39, or between 0.15 and 0.37, or between 0.17 and 0.35.

[0117] Yet another aspect of the present invention is the composite material as described above, wherein the passivation layer exhibits an N-parameter at attenuated total reflectance (ATR) of less than 0.7, measured as follows:

number

[0118] The N-parameter is also described in U.S. Pat. No. 8,067,070 and is measured similarly to the O-parameter, except that the intensity at two specific wave numbers is used, and neither of these wave numbers is a range. U.S. Pat. No. 8,078,070 claims a passivation layer having an N-parameter between 0.7 and 1.6. Again, the inventors have produced better coatings using a pH protective coating or layer 286 with an N-parameter below 0.7, as discussed above. Alternatively, the value of the N-parameter is at least 0.3, or between 0.4 and 0.6, or at least 0.53.

[0119] The rate of corrosion, dissolution, or leaching (different names for related concepts) of the pH protective coating or layer 286 when in direct contact with the fluid 218 is slower than the rate of corrosion of the barrier coating or layer 288 when in direct contact with the fluid 218 .

[0120] In any embodiment, a thickness of the pH protective coating or layer from 50 to 500 nm is contemplated, with a preferred range of 100 to 200 nm.

[0121] The pH protective coating or layer 286 is effective to separate the fluid 218 from the barrier coating or layer 288 for a sufficient period of time to allow the barrier coating to function as a barrier during the useful shelf-life of the pharmaceutical package or other container 210 .

[0122] The inventors have further realized that certain pH protective coatings or layers of SiOxCy or Si(NH)xCy formed from polysiloxane precursors, where the pH protective coating or layer has a substantial organic component, do not corrode rapidly when exposed to fluids, and in fact corrode or dissolve more slowly when the fluid has a higher pH in the range of 5-9. For example, at pH 8, the dissolution rate of a pH protective coating or layer made of octamethylcyclotetrasiloxane, i.e., OMCTS, is very slow. Thus, these SiOxCy or Si(NH)xCy pH protective coatings or layers can be used to cover a barrier layer of SiOx, preserving the benefits of the barrier layer by protecting it from fluids in pharmaceutical packaging. A protective layer is deposited on at least a portion of the SiOx layer to protect the SiOx layer from the contents stored in the container that would otherwise come into contact with the SiOx layer.

[0123] SiOxCy or Si(NH)xCy coatings can also be deposited from linear siloxane or linear silazane precursors, such as hexamethyldisiloxane (HMDSO) or tetramethyldisiloxane (TMDSO).

[0124] Optionally, the FTIR absorption spectrum of the pH protective coating or layer 286 of any embodiment has a ratio between the maximum amplitude of the Si-O-Si symmetric stretching peak, typically between about 1000 and 1040 cm-1, and the maximum amplitude of the Si-O-Si asymmetric stretching peak, typically between about 1060 and about 1100 cm-1, greater than 0.75. Alternatively, in any embodiment, this ratio can be at least 0.8, or at least 0.9, or at least 1.0, or at least 1.1, or at least 1.2. Alternatively, in any embodiment, this ratio can be at most 1.7, or at most 1.6, or at most 1.5, or at most 1.4, or at most 1.3. As with the alternative embodiments of the invention of Figures 1-7, any minimum ratio specified herein can be combined with any maximum ratio specified herein.

[0125] Optionally, in either embodiment, the pH protective coating or layer 286, in the absence of an agent, has a non-oily appearance, which has been observed in some instances to distinguish an effective pH protective coating or layer from a lubricious layer, which in some cases has been observed to have an oily (i.e., shiny) appearance.

[0126] Optionally, with respect to the pH protective coating or layer 286 in any embodiment, the total silicon content of the pH protective coating or layer and the barrier coating, when dissolved in a test composition at pH 8 from the container, is less than 66 ppm, or less than 60 ppm, or less than 50 ppm, or less than 40 ppm, or less than 30 ppm, or less than 20 ppm.

[0127] Protocol involving multiple layers coated in the same device Optionally, in any embodiment, the bonding or adhesive coating or layer, the optional barrier coating or layer, the optional pH protective layer, and the optional water barrier coating are deposited in the same apparatus without breaking the vacuum between two or more coating steps, such as between the deposition of the adhesive coating or layer and the barrier coating or layer, or optionally between the barrier coating or layer and the pH protective coating or layer, or optionally between the pH protective coating and the water barrier coating. During the process, a partial vacuum is drawn in the interior space. With the partial vacuum in the interior space remaining unbroken, a bonding coating or layer of SiOxCy is deposited by a bonding PECVD coating process. The bonding PECVD coating process is carried out by supplying gases suitable for forming the coating while applying sufficient power to generate a plasma in the interior space. The gas supply includes a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent. The values ​​of x and y are determined by X-ray photoelectron spectroscopy (XPS). The plasma is then extinguished, with the partial vacuum in the interior space remaining unbroken. As a result, a bond coating or layer of SiOxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3, is produced on the interior surface.

[0128] At a later stage in the process, without breaking the partial vacuum in the interior space, a barrier coating or layer is deposited by a barrier PECVD coating process. The barrier PECVD coating process is performed by supplying a gas while applying sufficient power to generate a plasma in the interior space. The gas supply includes a linear siloxane precursor and oxygen. As a result, a barrier coating or layer of SiOx, with x between 1.5 and 2.9 as characterized using XPS, is produced between the bond coating or layer and the interior space.

[0129] The plasma is then optionally extinguished while leaving the partial vacuum in the interior space uninterrupted.

[0130] Alternatively, a pH protective coating or layer of SiOxCy can then be deposited, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3, each as determined by XPS. The pH protective coating or layer is optionally deposited between the barrier coating or layer and the interior space by a pH protective PECVD coating process, which includes providing a gas including a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent, while applying sufficient power to generate a plasma within the interior space.

[0131] At a later stage in the process, without breaking the partial vacuum, a water barrier coating or layer is deposited by a water barrier coating PECVD process. The water barrier PECVD coating process is performed by supplying a gas while applying sufficient power to generate a plasma. The gas supply includes fluorocarbon and / or hydrocarbon precursors. As a result, a water barrier coating or layer is produced on top of the pH protective coating.

[0132] Optionally, in any embodiment, the PECVD process for depositing a bond coating or layer, a barrier coating or layer, or a pH protective coating or layer, or a water barrier coating, or any combination of two or more thereof, is performed by applying pulsed power (alternatively, the same concept is referred to as "energy" herein) to generate a plasma within the interior space.

[0133] Alternatively, the combined PECVD coating process, or the barrier PECVD coating process, or the pH protective PECVD coating process, or the water barrier coating, or any combination of two or more thereof, can be performed by applying continuous power to generate a plasma within the interior space.

[0134] Optionally, a magnetic field can be applied in the vicinity of the container while electromagnetic energy is applied, for example, throughout the deposition step. The magnetic field is applied under conditions effective to reduce the standard deviation of the average thickness of the gas barrier coating on the generally cylindrical inner surface. Application of the magnetic field may improve the uniformity of the coating. Related apparatus and methods can be found in WO2014085348A2, WO2014085348A2, which are incorporated herein by reference in their entireties.

[0135] Three-layer coating parameters Examples of specific coating parameters that have been used to date for 1 mL containers and 5 mL vials are shown in PECVD Tri-Layer Process Specific Parameters Tables 2 (1 mL vials) and 3 (5 mL vials).

[0136] [Table 2]

[0137] [Table 3]

[0138] The O and N parameters for the pH protective coating or layer deposited on the 1 mL container mentioned above are 0.34 and 0.55, respectively.

[0139] The O and N parameters for a pH protective coating or layer deposited in a 5 mL container are 0.24 and 0.63, respectively.

[0140] To carry out the process, a container 210 is provided that consists essentially of a thermoplastic polymeric material and includes a wall 214 that defines an interior space 212. Optionally, in any embodiment, the wall comprises polyester, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyolefin, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polypropylene (PP), or polycarbonate, preferably COP. Optionally, in any embodiment, the volume of the container interior space is between 2 and 12 mL, optionally between 3 and 5 mL, and optionally between 8 and 10 mL.

[0141] The wall 214 has an inner surface facing the interior space and an outer surface.

[0142] A partial vacuum is drawn on the interior space. While leaving the partial vacuum unbroken within the interior space, a bonded coating or layer 289 of SiOxCy is deposited by a bonded PECVD process, which includes supplying a gas containing a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent, while applying sufficient power (alternatively, the same concept is referred to herein as "energy") to generate a plasma within the interior space. The values ​​of x and y are determined by X-ray photoelectron spectroscopy (XPS).

[0143] The plasma is then extinguished, without breaking the partial vacuum in the interior space, which has the effect of stopping the deposition of a bond coating or layer of SiOxCy. Optionally, in any embodiment, the supply of gases employed in the bond PECVD coating process can be stopped after the plasma used in the bond PECVD coating process is extinguished and before the barrier PECVD coating process is initiated. As a result, a bond coating or layer of SiOxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3, is produced on the interior surface.

[0144] At a later stage in the process, without breaking the partial vacuum within the interior space, a barrier coating or layer 288 is deposited by a barrier PECVD coating process, which involves supplying a linear siloxane precursor and a gas containing oxygen while applying sufficient power (alternatively, the same concept is referred to as "energy" herein) to generate a plasma within the interior space.

[0145] Optionally, in any of the embodiments, the power provided to generate a plasma within the interior space to deposit a barrier coating or layer in a 1-Up coater is between 30 and 80 Watts, optionally between 40 and 80 Watts, optionally between 50 and 80 Watts, optionally between 55 and 65 Watts, and in a 4-Up coater, optionally between 175 and 200 Watts, optionally between 180 and 190 Watts.

[0146] Optionally, in any embodiment, the plasma generated to deposit the barrier coating or layer is applied for a period of from 12 to 20 seconds, optionally from 15 to 20 seconds.

[0147] Optionally, in any embodiment, the barrier coating or layer is deposited using a siloxane precursor feed rate of 0.5-2 sccm, optionally 0.7-1.3 sccm, optionally of HMDSO.

[0148] Optionally, in any embodiment, the barrier coating or layer is deposited using a pressure of 0.5 to 3.5 Torr, optionally 1 to 2.5 Torr.

[0149] Optionally, after depositing the barrier coating or layer, the plasma is extinguished without breaking the partial vacuum in the interior space, which has the effect of stopping deposition of the barrier coating or layer. Optionally, in any embodiment, the supply of gases employed in the barrier PECVD coating process can be stopped after the plasma used in the barrier PECVD coating process is extinguished, and before the optional pH-protected PECVD coating process, if used, is started. As a result of the barrier coating, a barrier coating or layer of SiOx, with x between 1.5 and 2.9, as characterized using XPS, is produced between the bond coating or layer and the interior space.

[0150] Then, optionally, while the partial vacuum in the interior space is not broken, a pH protective coating or layer 286 of SiOxCy is later deposited by a pH protective PECVD process, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3, each as determined by XPS. The pH protective coating or layer is optionally deposited between the barrier coating or layer and the interior space by a pH protective PECVD coating process. The pH protective PECVD coating process includes supplying a gas including a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent, while applying sufficient power (alternatively, the same concept is referred to herein as "energy") to generate a plasma in the interior space.

[0151] Surprisingly, as a result of this processing, a coated vessel 210 produced by this process has a lower gas permeation rate constant into the interior space than a comparable vessel 210 produced by the same process, with the exception that the partial vacuum in the interior space is broken between the deposition of the bond coating or layer and the deposition of the barrier coating or layer.

[0152] Surprisingly, as a result of this processing, a coated vessel 210 produced by this process has a lower gas permeation rate constant into the interior space than a comparable vessel 210 produced by the same process, with the exception that the partial vacuum in the interior space is broken between the deposition of the bond coating or layer and the deposition of the barrier coating or layer.

[0153] Alternatively, a coated vessel produced by this process, including the optional steps, has a lower gas transmission rate constant into the interior space than a comparable vessel produced by the same process, except that the partial vacuum in the interior space is broken between the deposition of the bonding coating or layer and the deposition of the barrier coating or layer, and the partial vacuum in the interior space is broken between the deposition of the barrier coating or layer and the pH protective coating or layer. Optionally, in any embodiment, the oxygen transmission rate constant (OPRC) of the coated vessel 210 is between 0.002 and 0.1, optionally between 0.01 and 0.1, optionally between 0.14 and 0.05, optionally between 0.002 and 0.02, optionally between 0.003 and 0.12 μmol / day / cm2 / atm.

[0154] Another example of this process is coating a 6 mL COP vial. A three-layer coating as described in this embodiment of the invention is applied by adjusting the flow of a single organosilicon monomer (e.g., HMDSO) and oxygen between each layer and varying the PECVD generation power (without breaking the vacuum between any two layers).

[0155] A 6mL COP vial is placed in the vessel holder, sealed, and a vacuum is pulled on the vessel. The vial is used to facilitate storage while containing the fluid as described below. If a blood sample collection tube is used, proportional results are assumed. After pulling a vacuum, the precursor, oxygen, and argon gas supplies are introduced, and then at the end of the "plasma delay", the 13.56MHz continuous (i.e., not pulsed) RF power is turned on to form the bond coating or layer. The power is then turned off, the gas flow is adjusted, and after the plasma delay, the power is turned on for the second layer, i.e., the SiOx barrier coating or layer. This is then repeated for the third layer, after which the gas is turned off, the vacuum seal is opened, and the vessel is removed from the vessel holder. The layers are deposited in the following order: a bond layer, then a barrier layer, then a pH protection layer. An example of the process settings is as shown in the table below.

[0156] [Table 4]

[0157] In many applications, the thermoplastic walls of the container need to provide a barrier to both water vapor and atmospheric gases, including oxygen / nitrogen gases. However, creating a barrier for water vapor on a polymer substrate is different than creating a barrier for oxygen or nitrogen.

[0158] The water vapor barrier coatings of the present invention, made using fluorocarbon / hydrocarbon precursors, differ from SiOx and SiOxCy coatings, which are primarily O2 / N2 barriers, but are much less effective as water vapor barriers: SiOx is more frequently used for O2 gas barrier coatings.

[0159] Water molecules are polar molecules, whereas atmospheric gas permeants such as oxygen and nitrogen molecules are non-polar. Polar molecules such as water molecules attract other polar molecules through dipole-dipole interactions, especially hydrogen bonds. Hydrogen bonds between water molecules and oxygen-containing species in SiOx / SiOxCy coatings make it easier for water molecules to penetrate these coatings. Oxygen and nitrogen molecules are non-polar molecules and do not interact with these types of coatings. This may be the reason why SiOx / SiOxCy coatings are good barriers for O2 but are not effective for water vapor.

[0160] Without being limited to theory, the water vapor barrier coating of the present invention does not contain oxygen atoms that form strong hydrogen bonds with water molecules that facilitate the penetration of water molecules through the coating. The highly non-polar chemical groups in the water vapor barrier coating repel water molecules through hydrophobic interactions that limit its penetration ability. Therefore, compared to SiOx / SiOxCy coatings, the water vapor barrier coating exhibits high water vapor blocking properties.

[0161] The present invention provides a product having a water barrier surface and a product having both water barrier and oxygen barrier properties at the same time. For example, PET has excellent O2 barrier properties but poor water vapor barrier properties. PET blood collection tubes coated with the water vapor barrier coating of the present invention exhibit high water vapor barrier properties.

[0162] Water Vapor Transmission Rate Test Protocol The procedures described herein may be used to assess moisture ingress for any sealable container or package. Tools and Equipment Desiccant (or substance to be evaluated) Crimper / Aluminum Crimp / Plunger / Stopper 〇 Environmental room Vial or syringe 〇 Chemical balance Nitrile gloves · procedure ○ Use a Sharpie permanent marker to mark the container directly. Place a desiccant or the substance to be evaluated in each container. Seal the container Weigh the container on at least a 4-point balance and record the weight as time 0. Place the weighed container in a suitable environmental chamber. 〇 Remove the container from the environmental chamber at the timing specified in the test procedure / protocol / DB. Allow containers to equilibrate at room temperature for at least 10 minutes unless otherwise specified in the protocol / DB / test procedure. Weigh the container and record the weight chronologically Return the container to the environmental chamber Calculate the amount of water in the container by subtracting the final weight from the initial weight of the container and converting it to milligrams. Calculate the moisture ingress rate as the weight divided by the number of days in the environmental chamber. EXAMPLES

[0163] Example 1. Contact angles of polypropylene surfaces coated with water barrier coatings This experiment was conducted to evaluate how the present water barrier coating affects the water contact angle of a polymer surface. Eight polypropylene flat sheet samples were provided. All samples were coated with the water barrier coating according to the protocol described herein. The coating precursor was C4F8 and mixed with Ar gas.

[0164] After coating was completed, water contact angle values ​​were obtained for each sample surface by goniometer angle measurement of a water droplet on the sample surface according to ASTM D7334-08 "Standard Practice for Surface Wettability of Coatings, Substrates and Pigments by Advancing Contact Angle Measurement". The results are shown in the table below and images are displayed in Figure 3. The results show that the water barrier coated surfaces have consistently higher water contact angles than surfaces without the coating.

[0165] In this example, the contact angle of the uncoated polymer surface is <90 degrees, so water wets the surface and spreads on it. The water barrier coating of the water barrier coating increases the contact angle of the surface to an angle of >90 degrees, so water stays as a bead on the coating surface and does not spread on the surface. This can help reduce the water vapor transmission rate of the container.

[0166] [Table 5]

[0167] Example 2. Comparison of FTIR spectra of uncoated and water barrier coated exterior surfaces of polypropylene tubing The polypropylene tube A was coated on its outer surface with the water barrier coating of the present invention according to the method described in the "Water Barrier Coating" section, and the precursor used was C4F8. The other polypropylene tube B was coated on its outer surface with the water barrier coating of the present invention according to the method described in the "Water Barrier Coating" section, and the precursor used was C3F6. After the coating was completed, FTIR spectra were taken of the outer surfaces of the uncoated polypropylene tube (C), the polypropylene tube coated with the water barrier coating using C4F8 as a precursor (A), and the polypropylene tube coated with the water barrier coating using C3F6 as a precursor (B). The three FTIRs are displayed in Figure 4. The FTIR spectra clearly show that the uncoated surface and the surface coated with the water barrier coating of the present invention are clearly different.

[0168] Example 3. FTIR spectrum of the water barrier coating on the inside surface of a 10 mL COP vial A 10 mL COP vial was coated on its inside surface with a water barrier coating of the present invention according to the method described herein, the precursor used was C4F8. The coating parameters were as follows: Power frequency: 13.56MHz Precursor: Octafluorocyclobutane (C4F8) Gas flow rate: 5sccm ○ Carrier gas flow rate: 10sccm Base pressure: 20mTorr Coating pressure: 90mTorr Coating time: 5 seconds

[0169] After coating was completed, an FTIR spectrum was obtained on the coating surface and is shown in Figure 4 with peak values ​​and assignments in Figure 5.

[0170] Example 4. Investigation of the Water Vapor Transmission Rate (WVTR) of Water Vapor Barrier Coating (WVBC) and Additive Effect of Water Vapor Barrier Coating and Three-Layer Coating This experiment was conducted to evaluate the water vapor transmission rate and cumulative effect of water vapor barrier coatings and tri-layer coatings.

[0171] Three sets of containers were provided, each containing 200 COP vials. The first set of vials was coated on its inner surface only with a water vapor barrier coating according to the method described herein, the precursor used was C4F8. The coating parameters were as follows: Power frequency: 13.56MHz Precursor: Octafluorocyclobutane (C4F8) Gas flow rate: 5sccm ○ Carrier gas flow rate: 10sccm Base pressure: 20m Torr Coating pressure: 90mTorr Coating time: 5 seconds

[0172] The second set of vials was not coated. The third set of vials was coated on its interior surface with a water vapor barrier coating and then a tri-layer coating over the water vapor barrier coating using the same methods described herein for the water vapor barrier coating and tri-layer coating.

[0173] After coating was completed, the WVTR was measured for each vial. USP Physical Tests, specifically USP General <671> Vials were tested as a whole product with stoppers attached, according to the section "Containers--Performance Test Methods" and more specifically "Water Vapor Transmission Test Methods for Packaging Systems". The average WVTR and BIF for each set of vials was calculated. The calculated average WVTR and BIF results are shown in the table below and in FIG. 6. The results demonstrate that 1) containers coated with the water vapor barrier coating of the present invention have a lower WVTR than uncoated containers, and 2) containers coated with a water vapor barrier coating and a three-layer coating, with the three-layer coating on top of the water vapor barrier coating, have a lower WVTR than containers coated with only the water vapor barrier coating. The BIF of containers coated with both the water vapor barrier coating and the three-layer coating is better than containers coated with only the water vapor barrier coating. The additive effect between the water vapor barrier coating and the three-layer coating is a surprising finding, since typically the three-layer coating has little effect on the WVTR.

[0174] [Table 6]

Claims

1. A container having a wall defining an interior space of the container, the wall having an inner surface facing the interior space, an outer surface, and a plasma enhanced chemical vapor deposition (PECVD) coating, the PECVD coating comprising: A water barrier coating having a water contact angle of 80 to 180 degrees, the water barrier coating being comprised of a precursor comprising at least one of a saturated or unsaturated linear or cyclic aliphatic fluorocarbon having 1 to 10 carbon atoms and 4 to 20 fluorine atoms per molecule, a saturated or unsaturated hydrocarbon having 1 to 6 carbon atoms, a saturated or unsaturated hydrofluorocarbon having 1 to 6 carbon atoms per molecule, or any combination thereof; SiO with a thickness of 2 to 1000 nm x A gas barrier coating (x is 1.5 to 2.9) and SiO x C y or SiN x C y and x is 0.5 to 2.4 and y is 0.6 to 3 as measured by X-ray photoelectron spectroscopy (XPS), and x is 1.5 to 2.9 as measured by X-ray photoelectron spectroscopy (XPS), the gas barrier coating having an inner surface facing the interior space and an outer surface facing the inner surface of the wall, the gas barrier coating being capable of reducing ingress of atmospheric gases into the interior space; A container comprising:

2. The container of claim 1 , wherein the water barrier coating is between the gas barrier coating and the interior surface of the wall.

3. The SiO x C y or SiN x C y 3. The container of claim 2, wherein the coating comprising is a pH protective coating, the pH protective coating having an inner surface facing the interior space and an outer surface facing the inner surface of the gas barrier coating.

4. The SiO x C y or SiN x C y 3. The container of claim 2, wherein the coating comprising is a bond coating, said bond coating having an inner surface facing said gas barrier coating and an outer surface facing said water barrier coating.

5. The water barrier coating is deposited directly on the wall, and the gas barrier coatings are deposited on the water barrier coatings, the gas barrier coatings being comprised of SiO x 10. The container of claim 1, comprising a gas barrier coating, a pH protective coating, and a bond coating, said bond coating being in direct contact with said water barrier coating, and said SiOx gas barrier coating being between said bond coating and said pH protective coating.

6. A container having a wall defining an interior space of the container, the wall having an inner surface facing the interior space, an outer surface, and a plasma enhanced chemical vapor deposition (PECVD) coating group, the PECVD coating group having a water contact angle of 80 to 180 degrees and composed of a precursor including a saturated or unsaturated fluorocarbon having 1 to 6 carbon atoms, a saturated or unsaturated hydrocarbon having 1 to 6 carbon atoms, a saturated or unsaturated hydrofluorocarbon having 1 to 6 carbon atoms, or a combination of two or more thereof, and a SiO2 having a thickness of 2 to 1000 nm. x A gas barrier coating (x is 1.5 to 2.9) and SiO x C y or SiN x C y and wherein x is 0.5 to 2.4 and y is 0.6 to 3 as measured using XPS, and wherein x is 1.5 to 2.9 as measured using an X-ray photoelectron spectrometer (XPS).

7. 7. The container of claim 6, wherein the water barrier coating comprises an unsaturated fluorocarbon having from 2 to 6 carbon atoms.

8. The container of claim 1 , wherein the water barrier coating is in direct contact with the interior surface of the wall.

9. The container of claim 1 , wherein the water barrier coating is in direct contact with the exterior surface of the wall.

10. The container according to any one of claims 1 to 9, wherein the container comprising the water barrier coating has a Water Vapor Transmission Barrier Improvement Factor (BIF) of greater than 1.

11. 11. The container of claim 1, wherein the container has a water vapor transmission barrier improvement factor (BIF) of greater than 1 for at least one of water, dimethylsulfoxide (DMSO), ethanol, or any combination of two or more thereof.

12. 12. The container of any of claims 1-11, wherein at least a portion of the wall comprises an olefin polymer, polypropylene (PP), polyethylene (PE), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polymethylpentene, polystyrene, hydrogenated polystyrene, polycyclohexylethylene (PCHE), heteroatom substituted hydrocarbon polymer, polyester, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polybutylene terephthalate (PBT), polyvinylidene chloride (PVdC), polyvinyl chloride (PVC), polycarbonate, polylactic acid, epoxy resin, nylon, polyurethane polyacrylonitrile, polyacrylonitrile (PAN), ionomer resin, Surlyn® ionomer resin, or any combination, composition, or blend of any two or more of the foregoing materials.

13. 13. The container according to any of claims 1 to 12, which is a microplate, a centrifuge tube, a well plate, a microwell plate, a vial, a pipette, a bottle, a jar, a syringe, a cartridge, a flask, a cryovial, a blister package, an ampoule, a vacutainer, a specimen tube, a chromatography vial, a cosmetic container, a medical diagnostic straw, a sample vial, an assay tube, a transfer pipette, a reagent container, rigid or flexible tubing, or a Cobas® Liat® system container.

14. The container according to any one of claims 1 to 13, having a cylindrical internal space.

15. 15. The container of claim 14, wherein the interior space has an interior axial length to inside diameter aspect ratio of 1:1 to 20:

1.

16. A container according to any preceding claim, containing a lyophilised drug, a diagnostic reagent or a topical tissue adhesive.

17. A method for manufacturing a container according to any one of claims 1 to 16, comprising the steps of at least partially evacuating an area adjacent to a surface of the wall to form a partially evacuated area; providing a precursor of the water barrier coating to the partially evacuated region and generating a plasma in the partially evacuated region to form a water barrier coating supported by the wall adjacent the evacuated region; before or after the step of providing a precursor for the water barrier coating, providing a precursor gas for a first coating of the gas barrier coatings into the partially evacuated region and generating a plasma in the partially evacuated region to form a coating of the gas barrier coatings supported by the wall adjacent the evacuated region; The method includes:

18. 20. The method of claim 17, further comprising the step of: after delivering a precursor gas for a first coating of the gas barrier coating group, delivering a precursor gas for a second coating of the gas barrier coating group to the partially evacuated region and generating a plasma in the partially evacuated region to form a second coating of the gas barrier coating group supported by the wall adjacent the evacuated region.

19. 19. The method of claim 17 or 18, wherein the vacuum in the evacuated region is not interrupted between at least two of the delivering steps.

20. The method of any of claims 17 to 19, wherein the vacuum in the evacuated region is not interrupted between at least three of the delivering steps.

21. A process for producing a container or surface according to any one of claims 1 to 16.

22. A container processing system for manufacturing the container according to any one of claims 1 to 16.

23. Use of a container according to any one of claims 1 to 16 as a container for a lyophilized drug, a diagnostic reagent, or a topical tissue adhesive.

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