Closure for pharmaceutical formulations, method for manufacturing same, and rotary deposition apparatus for manufacturing same

Abstract

A closure for a pharmaceutical formulation, a method for manufacturing a closure for a pharmaceutical formulation, and a rotary deposition apparatus for manufacturing a closure for a pharmaceutical formulation are provided. The closure for a pharmaceutical formulation includes a polymeric closure body and at least one barrier layer over the polymeric closure body. Further, the at least one barrier layer includes an adhesion promoting layer material within at least a portion of a thickness of the at least one barrier layer proximate a surface of the polymeric closure body, and the adhesion promoting layer material includes SiOxCy: H. Further, the at least one barrier layer includes a barrier layer material within at least a portion of a surface of a thickness of the at least one barrier layer remote from the polymeric closure body, and the barrier layer material is selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

Description

Technical Field

[0001] Embodiments of the present disclosure relate to a closure for a pharmaceutical formulation, a method for manufacturing a closure for a pharmaceutical formulation, and a spin deposition apparatus for manufacturing a closure for a pharmaceutical formulation. Background Art

[0002] Recently, the development of new pharmaceutical agents (including monoclonal antibodies, cell and gene therapies, vaccines, and recombinant proteins and peptides) and the corresponding marketing authorizations have increased rapidly. In this regard, one of the most notable examples in recent years is the development and subsequent market launch of the COVID-19 vaccine.

[0003] Protecting such drug formulations from undesirable interactions with the surrounding environment and maintaining the efficacy of drug formulations during shelf life is one of the most pressing challenges in the pharmaceutical industry.

[0004] Pharmaceutical preparations, in particular biopharmaceuticals, are mainly provided as liquids or lyophilized formulations in container systems, such as glass containers closed with polymer closures, which are also referred to as parental closures or closures for pharmaceutical preparations. Synthetic rubber closures are the first choice for parental closures because of their higher purity and remarkable material properties, in particular their elasticity. The elasticity leads to a closer contact with the glass container and thus ensures the integrity and sterility of the contained pharmaceutical preparation. In addition, rubber has sufficient resealing ability to allow repeated punctures with a needle. Therefore, closures for pharmaceutical preparations can exist in the form of stoppers, plungers and needle shields.

[0005] In order to achieve the necessary material properties of the closure for pharmaceutical preparations, additives such as plasticizers, fillers, antioxidants and pigments must be added during the manufacture of the closure for pharmaceutical preparations. These substances are not covalently bound to the polymer chains of the closure for pharmaceutical preparations, and therefore during the shelf life of the pharmaceutical preparation, these substances may migrate from the closure into the pharmaceutical preparation itself. The migration of substances (also referred to as extractables or leachables) should be minimized, because such migration may have a negative impact on the safety, stability and efficacy of the pharmaceutical preparation.

[0006] In view of the above, there is a need for closures for pharmaceutical preparations having improved barrier properties against migration of substances (e.g., extractables or leachables) and also having water vapor and oxygen barrier properties, which also help to maintain the desired properties of the pharmaceutical preparation for a longer period of time. In addition, there is a need for methods for manufacturing such closures for pharmaceutical preparations that are relatively easy and cost-effective to perform and provide such closures for pharmaceutical preparations having the above-mentioned properties. In addition, there is a need for equipment for manufacturing such closures for pharmaceutical preparations that allows these closures for pharmaceutical preparations to be manufactured on an industrial scale and at a high level of productivity. Summary of the invention

[0007] In view of the above, a closure for a pharmaceutical preparation, a method for manufacturing a closure for a pharmaceutical preparation, and a rotary deposition apparatus for manufacturing a closure for a pharmaceutical preparation are provided. Other aspects, advantages, and features of the disclosure are apparent from the claims, description, and drawings.

[0008] According to one aspect of the present disclosure, a closure for a pharmaceutical preparation is provided. The closure for a pharmaceutical preparation comprises a polymer closure body and at least one barrier layer, wherein the at least one barrier layer is above the polymer closure body. In addition, at least one barrier layer comprises an adhesion promoting layer material, wherein the adhesion promoting layer material is within at least a portion of the thickness of the at least one barrier layer close to the surface of the polymer closure body, and the adhesion promoting layer material comprises SiOxCy:H. In addition, at least one barrier layer comprises a barrier layer material, wherein the barrier layer material is within at least a portion of the thickness of the at least one barrier layer away from the surface of the polymer closure body, and the barrier layer material is selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

[0009] According to one aspect of the present disclosure, a method for manufacturing a closure for a pharmaceutical preparation is provided. The method includes: providing at least one polymer closure body; and forming at least one barrier layer above the at least one polymer closure body. In addition, forming at least one barrier layer above the at least one polymer closure body includes sequentially depositing an adhesion promoting layer material and depositing at least one barrier layer material. In addition, at least one barrier layer includes an adhesion promoting layer material, and the adhesion promoting layer material is within at least a portion of the thickness of at least one barrier layer close to the surface of at least one polymer closure body, and the adhesion promoting layer material includes SiOxCy:H. In addition, at least one barrier layer includes at least one barrier layer material, and the at least one barrier layer material is within at least a portion of the thickness of at least one barrier layer away from the surface of at least one polymer closure body, and the barrier layer material is selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

[0010] According to one aspect of the present disclosure, a rotary deposition apparatus for manufacturing a closure for a pharmaceutical formulation is provided. The rotary deposition apparatus comprises: a vacuum chamber; a rotary container located within the vacuum chamber and configured to hold at least one polymer closure body inside; and at least one deposition source connected to the vacuum chamber, located outside the vacuum chamber and configured to deposit at least one barrier layer on the polymer closure body. In addition, the rotary container comprises a perforated wall configured to allow deposition of at least one barrier layer on the polymer closure body. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to be able to understand in detail the manner in which the above-mentioned features of the present disclosure are achieved, a more specific description of the present disclosure briefly summarized above may be made by reference to the embodiments. The accompanying drawings relate to the embodiments of the present disclosure and are described below:

[0012] Figure 1 shows an example of a closure for a pharmaceutical preparation and a corresponding schematic cross-sectional view of a portion of a closure for a pharmaceutical preparation according to an embodiment described herein;

[0013] Figures 2 to 5 shows a schematic cross-sectional view of a portion of a closure for a pharmaceutical preparation according to an embodiment described herein;

[0014] Figure 6 A flow chart showing a method for manufacturing a closure for a pharmaceutical preparation according to an embodiment described herein;

[0015] Figure 7 and Figure 8 shows a schematic diagram of a rotary deposition apparatus for manufacturing a closure for a pharmaceutical formulation according to an embodiment described herein; and

[0016] Fig. 9 A schematic diagram of a rotating container of a rotary deposition apparatus for manufacturing closures for pharmaceutical formulations according to embodiments described herein is shown. DETAILED DESCRIPTION

[0017] Reference will now be made in detail to various embodiments of the present disclosure, one or more examples of which are illustrated in the accompanying drawings. In the following description of the drawings, the same reference numerals denote the same features. Typically, only the differences with respect to a single embodiment are described. Each example is provided as an explanation of the present disclosure, but this is not meant to limit the present disclosure. In addition, features depicted or described as part of one embodiment may be used on other embodiments or used in conjunction with other embodiments to produce yet another embodiment. This specification is intended to include such modifications and changes.

[0018] The rapid growth in the development and, thus, marketing authorization of pharmaceutical preparations, including monoclonal antibodies, cell and gene therapies, vaccines, and recombinant proteins and peptides, requires further improvements in the production of container systems for pharmaceutical preparations to meet the high demand for such container systems.

[0019] Protecting drug formulations from undesired interactions with the surrounding environment and maintaining their efficacy during shelf life constitutes one of the most pressing challenges in the pharmaceutical industry.

[0020] Pharmaceutical preparations, in particular biopharmaceuticals, are mainly provided as liquids or lyophilized formulations in container systems, such as glass containers closed with polymer closures, also referred to as parent closures or closures for pharmaceutical preparations. Closures for pharmaceutical preparations, in particular synthetic rubber closures, are often chosen because of their higher purity and remarkable material properties, in particular their elasticity. The elasticity results in a closer contact with the glass container and thus ensures the integrity and sterility of the contained pharmaceutical preparation.

[0021] Since such container systems are sterile before being placed on the market, maintaining the seal integrity itself is critical to maintaining the sterility of the drug preparation until the drug preparation is administered to the patient. Therefore, closures for drug preparations may exist as stoppers, plungers, and needle shields in container systems for drug preparations.

[0022] In order to achieve the necessary material properties of the closure for pharmaceutical preparations, additives such as plasticizers, fillers, antioxidants and pigments must be added during the manufacture of the closure for pharmaceutical preparations. These substances are not covalently bound to the polymer chains of the closure for pharmaceutical preparations, and therefore during the shelf life of the pharmaceutical preparation, these substances may migrate from the closure for pharmaceutical preparations into the pharmaceutical preparation. The migration of such substances (also referred to as extractables or leachables) should be minimized, because the migration may affect the safety, stability and efficacy of the pharmaceutical preparation.

[0023] Since migration from closures for pharmaceutical preparations may lead to such disadvantages, it is desirable for closures for pharmaceutical preparations to have improved performance, particularly barrier properties to extractables or leachables. In addition, it is also desirable for closures for pharmaceutical preparations to exhibit water vapor and oxygen barrier properties, which also help to maintain the desired properties of the pharmaceutical preparation for a longer period of time.

[0024] In view of the above, in addition to improving the production of container systems for pharmaceutical preparations to meet the high demand for such container systems on the market, there is a need to further improve the barrier properties of closures for pharmaceutical preparations, such as the barrier properties against extractables or leachables, water vapor and oxygen.

[0025] Furthermore, there is a need for methods for manufacturing such closures for pharmaceutical preparations which are relatively easy and cost-effective to carry out and which provide such closures for pharmaceutical preparations having the above-mentioned properties. Furthermore, there is a need for equipment for manufacturing such closures for pharmaceutical preparations which allows manufacturing such closures for pharmaceutical preparations on an industrial scale and at a high level of productivity.

[0026] The present disclosure satisfies the above needs by providing a closure for a pharmaceutical preparation, a method for manufacturing a closure for a pharmaceutical preparation, and a rotary deposition apparatus for manufacturing a closure for a pharmaceutical preparation. In particular, since the closure for a pharmaceutical preparation of the present disclosure includes at least one barrier layer, the at least one barrier layer includes: an adhesion promoting layer material, the adhesion promoting layer material includes SiOxCy; and a barrier layer material, the barrier layer material is selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof, the closure for a pharmaceutical preparation of the present disclosure exhibits improved barrier properties, for example, barrier properties against extractables or leachables, water vapor, and oxygen.

[0027] Furthermore, due to the location of the adhesion promoting layer material and the barrier layer material within the at least one barrier layer, the at least one barrier layer exhibits an appropriate balance between flexural rigidity and crack initiation strain (i.e., fracture toughness), and thus the at least one barrier layer is able to withstand significant levels of mechanical strain and match the mechanical properties of the polymer closure body. In particular, the adhesion promoting layer material provides an intermediate region between the barrier layer material and the polymer closure body, which acts as a mechanical buffer for mechanical strain.

[0028] Furthermore, the method for manufacturing a closure for pharmaceutical preparations of the present disclosure allows for reduced production costs and time due to the simplicity of depositing at least one barrier layer on the polymeric closure body, and allows for adjusting the barrier properties of the closure for pharmaceutical preparations by depositing further barrier layers having different barrier layer materials.

[0029] Furthermore, the rotary deposition apparatus for manufacturing a closure for a pharmaceutical preparation of the present disclosure allows the manufacture of closures for pharmaceutical preparations on an industrial scale, i.e., at a mass production level and at a high productivity level. In addition, since the rotary deposition apparatus comprises a rotary container, in which a polymeric closure body or a plurality of polymeric closure bodies are rotated during the manufacture of the closure for the pharmaceutical preparation, the deposition of at least one barrier layer over the polymeric closure body is uniform over the entire polymeric closure body. Furthermore, due to the combination of the rotary container and at least one deposition source, at least one barrier layer is deposited even on the most inaccessible parts of the surface of the polymeric closure body or a plurality of polymeric closure bodies.

[0030] Before describing various embodiments of the present disclosure in more detail, some aspects regarding some terms and expressions used herein are explained.

[0031] The term "pharmaceutical preparation" as used herein refers in particular to a medicament in the form of a finished dosage form of a pharmaceutical preparation, e.g. intended for human or veterinary medicine and in particular for the treatment of a disease or injury. The term "pharmaceutical preparation" as used herein may in particular also include materials for the preparation and / or formulation of a finished dosage form of a medicament, e.g. intended for human or veterinary medicine and in particular for the treatment of a disease or injury.

[0032] In particular, the term "drug" as used herein includes vaccines, antibodies, cells, genes, blood factors, proteins, recombinant proteins, peptides and hormones, such as intended for human or veterinary medicine and in particular for the treatment of disease or injury. In particular, the term "drug" as used herein may also refer to any natural or artificially prepared chemical, such as intended for human or veterinary medicine and in particular for the treatment of disease or injury.

[0033] In particular, the term "polymer closure body" may be understood as a seal made of a polymer for closing any type of container, such as a vial, bottle or syringe made of glass or plastic for pharmaceutical preparations. In particular, the term "polymer closure body" may refer to a stopper, plunger and / or needle shield made of a polymer for closing any type of container, such as a vial, bottle or syringe made of glass or plastic for pharmaceutical preparations.

[0034] The term "elastomer" or "elastomeric" refers in particular to a natural or synthetic polymer having elastic properties, i.e. capable of undergoing a large degree of elastic deformation. Examples of polymers, in particular synthetic rubbers, used or comprised in a polymer closure body or polymer closure bodies, in particular synthetic rubber closure bodies, are copolymers of styrene and butadiene, polyisoprene and halogenated copolymers of isobutylene and isoprene, such as bromobutyl rubber or chlorobutyl rubber.

[0035] The term "barrier layer" may be understood in particular as a layer made of a barrier material, in particular formed on a substrate, such as formed on a polymer closure body, and more particularly formed on a synthetic rubber closure body. The term "barrier layer" may be understood in particular as a layer made of a barrier material, in particular formed on a substrate surface, such as formed on a surface of a polymer closure body, and more particularly formed on a surface of a synthetic rubber closure body. In particular, the term "barrier layer" may also be understood as a layer made of a barrier material, said layer comprising barrier properties, such as preventing the migration of extractables or leachables from a polymer closure body, in particular a synthetic rubber closure body, to water vapor and oxygen.

[0036] In particular, the term "extractables" as used herein refers to organic and / or inorganic chemicals released from a polymeric closure body, in particular a synthetic rubber closure body, under laboratory conditions, i.e. under the influence of accelerated or excessive temperature, solvents or surface exposure. In particular, the term "leachables" as used herein refers to organic and / or inorganic chemicals released from a polymeric closure body, in particular a synthetic rubber closure body, during storage of a pharmaceutical formulation under normal temperature and / or pressure conditions in which the pharmaceutical formulation is stored.

[0037] In particular, the term "gradient chemical composition" as used herein refers to a chemical composition that changes gradually, for example over the thickness of a layer, in particular in a vertical direction relative to the surface of the polymer closure body.

[0038] When referring to the terms "on", "above" or "subsequently", such as at least one barrier layer above the polymeric closure body or a second barrier layer above the first barrier layer, it is understood that the terms "on", "above" or "subsequently" are used to define the order of layers, where the starting point is the substrate, i.e. the polymeric closure body. The order is independent of whether the closure for a pharmaceutical formulation (e.g., including at least one barrier layer) is depicted upside down.

[0039] Figure 1 An example of a closure 100 for a pharmaceutical preparation and a corresponding schematic cross-sectional view of a portion of a closure 100 for a pharmaceutical preparation according to embodiments described herein are shown.

[0040] Although various embodiments of the present disclosure are described with reference to the closure 100 for pharmaceutical preparations for simplicity, the various embodiments with reference to the closure 100 for pharmaceutical preparations of the present disclosure may also be applicable to or reference other closures for pharmaceutical preparations described in the present disclosure.

[0041] According to some embodiments that may be combined with other embodiments described herein, a closure 100 for a drug formulation includes a polymeric closure body 110. In addition, the closure 100 for a drug formulation includes at least one barrier layer 160, the at least one barrier layer being above the polymeric closure body 110. In addition, the at least one barrier layer 160 includes an adhesion promoting layer material, the adhesion promoting layer material being within at least a portion of the thickness of the at least one barrier layer 160 (particularly in a perpendicular direction relative to the surface of the polymeric closure body 110) close to the surface of the polymeric closure body 110. In addition, the adhesion promoting layer material includes SiOxCy:H. In some embodiments, the at least one barrier layer 160 may have a sufficiently high degradation temperature to remain stable during subsequent processing (e.g., sterilization of the closure 100 for a drug formulation, which may involve extreme temperatures).

[0042] In addition, at least one barrier layer 160 includes a barrier material that is away from the surface of the polymer enclosure body 110 within at least a portion of the thickness of the at least one barrier layer 160 (particularly in a perpendicular direction relative to the surface of the polymer enclosure body 110). In addition, the barrier material is selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

[0043] Due to the presence of the adhesion promoting layer material and the barrier layer material in the closure 100 for drug preparations as described above, the closure 100 for drug preparations of the present disclosure exhibits improved barrier properties, such as barrier properties against extractables or leachables, water vapor, and oxygen.

[0044] Furthermore, due to the location of the adhesion promoting layer material and the barrier layer material within the at least one barrier layer 160 as described above, the at least one barrier layer 160 exhibits an appropriate balance between bending stiffness and crack initiation strain (i.e., fracture toughness), and thus the at least one barrier layer 160 is able to withstand significant levels of mechanical strain and match the mechanical properties of the polymer closure body 110. In particular, the adhesion promoting layer material provides an intermediate region between the barrier layer material and the polymer closure body 110, which acts as a mechanical buffer for the mechanical strain.

[0045] In some embodiments, the polymer closure body 110 may include at least one polymer selected from the group consisting of: copolymers of styrene and butadiene, polyisoprene, halogenated copolymers of isobutylene and isoprene (such as bromobutyl rubber or chlorobutyl rubber), and combinations thereof. In some embodiments, the polymer closure body 110 may be a synthetic rubber closure body. In some embodiments, the polymer closure body 110 may have a three-dimensional shape or structure. In some embodiments, the polymer closure body 110 may be a stopper, a plunger, or a needle shield.

[0046] In some embodiments, at least one barrier layer 160 may have a thickness of 500 nm or less, in particular, 480 nm or less, and more in particular, 460 nm or less; and / or at least one barrier layer 160 may have a thickness of 120 nm or more, in particular, 140 nm or more, and more in particular, 160 nm or more. In some embodiments, at least one barrier layer 160 may have a thickness of 120 nm or more and 500 nm or less, in particular, 140 nm or more and 480 nm or less, and more in particular, 160 nm or more and 460 nm or less.

[0047] In some embodiments, at least one barrier layer 160 may have a thickness less than 10 -1 g / m 2 / day water vapor transmission rate, especially less than 10 -2 g / m 2 / day water vapor transmission rate and more particularly 10 -3 g / m 2 Water vapor transmission rate (WVTR) can be measured according to ISO 2528:2017.

[0048] In some embodiments, at least one barrier layer 160 may have a relative humidity of less than 10°C and 0%. -1 ml / m 2 / day oxygen transmission rate, especially less than 10-2 ml / m 2 / day oxygen transmission rate and more particularly 10 -3 ml / m 2 Oxygen transmission rate per day. The oxygen transmission rate can be measured according to ISO 15105-1:2007.

[0049] In some embodiments, at least one barrier layer 160 may include barrier properties that prevent the migration of extractables, particularly leachables, from the polymer closure body 110. In some embodiments, the extractables, particularly leachables, may include at least one chemical from the group consisting of phthalates, trialkylbenzene-1,2,4-tricarboxylates, and combinations thereof.

[0050] In some embodiments, the at least one barrier layer 160 can be disposed or deposited directly over the polymer closure body 110. In some embodiments, no other layers or films are present between the polymer closure body 110 and the at least one barrier layer 160.

[0051] In some embodiments, the barrier material may include SiO2, and the at least one barrier layer 160 may include a first barrier layer above the polymer enclosure body 110, the first barrier layer having a gradient chemical composition across the thickness of the first barrier layer, particularly in a vertical direction relative to the surface of the polymer enclosure body 110, such as Figure 1 exemplarily shown in FIG.

[0052] Therefore, if Figure 1 As shown in an exemplary manner in FIG. 1 , at least one barrier layer 160 may correspond to a first barrier layer having a gradient chemical composition, wherein the gradient chemical composition is represented in an exemplary manner by a color transition across the thickness of the first barrier layer, in particular in a vertical direction relative to the surface of the polymer closure body. Figure 1 As shown in an exemplary manner, Figure 1 The dark portion of the first barrier layer in the graph corresponds to a portion of the thickness of the first barrier layer close to the surface of the polymer enclosure body 110, and the colorless portion of the first barrier layer corresponds to a portion of the thickness of the first barrier layer away from the surface of the polymer enclosure body 110.

[0053] In some embodiments, the gradient chemical composition may include a first chemical composition corresponding to an adhesion promoting layer material within at least a portion of the thickness of the first barrier layer (particularly in a direction perpendicular to the surface of the polymer enclosure body 110) close to the surface of the polymer enclosure body 110. In some embodiments, the gradient chemical composition may further include a second chemical composition corresponding to a barrier layer material within at least a portion of the thickness of the first barrier layer (particularly in a direction perpendicular to the surface of the polymer enclosure body 110) away from the surface of the polymer enclosure body 110.

[0054] In some embodiments, the surface of the polymer closure body 110 may be treated (by providing (e.g., depositing) at least one barrier layer on the surface) to improve adhesion. Useful surface treatments may include discharge (e.g., plasma, glow discharge, corona discharge, dielectric barrier discharge, or atmospheric pressure discharge) in the presence of a suitable reactive or non-reactive atmosphere; chemical pretreatment; or flame pretreatment.

[0055] Figure 2 2 shows a schematic cross-sectional view of a portion of a closure 200 for a pharmaceutical preparation according to other embodiments described herein. Figure 2 For simplicity, similar Figure 1 A depiction of the entire closure 200 for pharmaceutical preparations of the closure 100 for pharmaceutical preparations in FIG.

[0056] According to some embodiments that can be combined with other embodiments described herein, a closure 200 for drug formulations includes a polymeric closure body 210. In addition, the closure 200 for drug formulations includes at least one barrier layer 260, the at least one barrier layer being above the polymeric closure body 210. In addition, the at least one barrier layer 260 includes an adhesion promoting layer material, the adhesion promoting layer material being close to the surface of the polymeric closure body 210 within at least a portion of the thickness of the at least one barrier layer 260 (particularly in a perpendicular direction relative to the surface of the polymeric closure body 210).

[0057] In addition, at least one barrier layer 260 includes a barrier layer material that is away from the surface of the polymer closure body 210 within at least a portion of the thickness of the at least one barrier layer 260 (particularly in a perpendicular direction relative to the surface of the polymer closure body 210).

[0058] In addition, if Figure 2As shown in an exemplary manner in FIG. 1 , at least one barrier layer 260 may include an adhesion promoting layer 215 overlying the polymer closure body 210. Additionally, at least one barrier layer 260 may include a first barrier layer 220 overlying the adhesion promoting layer 215. In this particular example, the adhesion promoting layer 215 may include an adhesion promoting layer material.

[0059] According to some embodiments, which can be combined with other embodiments described herein, the first barrier layer 220 may include a barrier layer material.

[0060] In some embodiments, the adhesion promoting layer 215 can be disposed or deposited directly over the polymer closure body 210. In some embodiments, the first barrier layer 220 can be disposed or deposited directly over the adhesion promoting layer 215. In some embodiments, no other layers or films are present between the polymer closure body 210 and the adhesion promoting layer 215. In some embodiments, no other layers or films are present between the adhesion promoting layer 215 and the first barrier layer 220.

[0061] According to some embodiments that can be combined with other embodiments described herein, the adhesion promoting layer 215 can have a thickness equal to or less than 350 nm, in particular a thickness equal to or less than 330 nm, and more particularly a thickness equal to or less than 310 nm. In some embodiments, the adhesion promoting layer 215 can have a thickness equal to or greater than 100 nm, in particular a thickness equal to or greater than 120 nm, and more particularly a thickness equal to or greater than 140 nm. In some embodiments, the adhesion promoting layer 215 can have a thickness of 100 nm or more and 350 nm or less, in particular a thickness of 120 nm or more and 330 nm or less, and more particularly a thickness of 140 nm or more and 310 nm or less.

[0062] According to some embodiments that can be combined with other embodiments described herein, the first barrier layer 220 may have a thickness equal to or less than 150 nm, particularly equal to or less than 130 nm, and more particularly equal to or less than 110 nm. In some embodiments, the first barrier layer 220 may have a thickness equal to or greater than 20 nm, particularly equal to or greater than 40 nm, and more particularly equal to or greater than 60 nm. In some embodiments, the first barrier layer 220 may have a thickness of 20 nm or more and 150 nm or less, particularly 40 nm or more and 130 nm or less, and more particularly 60 nm or more and 110 nm or less.

[0063] Figures 3 to 5 1 shows a schematic cross-sectional view of a portion of a closure 300, 400, 500 for a pharmaceutical preparation according to an embodiment described herein. Figure 2For simplicity, the descriptions are omitted. Figure 1 100 for a closure for a pharmaceutical preparation is depicted as a whole closure 300 , 400 , 500 for a pharmaceutical preparation.

[0064] According to some embodiments that can be combined with other embodiments described herein, the closure 300, 400, 500 for drug formulations includes a polymeric closure body 310, 410, 510. In addition, the closure 300, 400, 500 for drug formulations includes at least one barrier layer 360, 460, 560, which is above the polymeric closure body 310, 410, 510. In addition, at least one barrier layer 360, 460, 560 includes an adhesion promoting layer material, which is close to the surface of the polymeric closure body 310, 410, 510 within at least a portion of the thickness of the at least one barrier layer 360, 460, 560 (particularly in a perpendicular direction relative to the surface of the polymeric closure body 310, 410, 510).

[0065] In addition, at least one barrier layer 360, 460, 560 includes a barrier layer material that is within at least a portion of the thickness of at least one barrier layer 360, 460, 560 away from the surface of the polymer closure body 310, 410, 510 (particularly in a perpendicular direction relative to the surface of the polymer closure body 310, 410, 510).

[0066] In addition, if Figure 3 As shown in an exemplary manner in FIG. 1 , at least one barrier layer 360 may include an adhesion promoting layer 315, which is above the polymer closure body 310. In addition, at least one barrier layer 360 may include a first barrier layer 320, which is above the adhesion promoting layer 315. In addition, at least one barrier layer 360 may include a second barrier layer 330, which is above the first barrier layer 320. In this particular example, the adhesion promoting layer 315 may include an adhesion promoting layer material.

[0067] According to some embodiments, which can be combined with other embodiments described herein, the second barrier layer 330 may include a barrier material. In addition, the first barrier layer 320 and the second barrier layer 330 may include different barrier materials selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof. As an example, the first barrier layer 320 and the second barrier layer 330 may be in the following order: SixNy / SixCy.

[0068] In some embodiments, the second barrier layer 330 can be disposed or deposited directly over the first barrier layer 320. In some embodiments, no other layers or films exist between the first barrier layer 320 and the second barrier layer 330.

[0069] According to some embodiments that can be combined with other embodiments described herein, the second barrier layer 330 may have a thickness equal to or less than 150 nm, particularly equal to or less than 130 nm, and more particularly equal to or less than 110 nm. In some embodiments, the second barrier layer 330 may have a thickness equal to or greater than 20 nm, particularly equal to or greater than 40 nm, and more particularly equal to or greater than 60 nm. In some embodiments, the second barrier layer 330 may have a thickness of 20 nm or more and 150 nm or less, particularly 40 nm or more and 130 nm or less, and more particularly 60 nm or more and 110 nm or less.

[0070] exist Figure 4 In the embodiment, the closure 400 for the pharmaceutical preparation is similar to Figure 3 The closure 300 for a pharmaceutical preparation is different in that at least one barrier layer 460 includes other barrier layers, such as a third barrier layer 440.

[0071] In addition, if Figure 4 4, at least one barrier layer 460 may include an adhesion promoting layer 415 overlying the polymer closure body 410. Additionally, at least one barrier layer 460 may include a first barrier layer 420 overlying the adhesion promoting layer 415. Additionally, at least one barrier layer 460 may include a second barrier layer 430 overlying the first barrier layer 420. Additionally, at least one barrier layer 460 may include a third barrier layer 440 overlying the second barrier layer 430. In this particular example, the adhesion promoting layer 415 may include an adhesion promoting layer material.

[0072] According to some embodiments that can be combined with other embodiments described herein, the third barrier layer 440 may include a barrier material. In addition, the first barrier layer 420, the second barrier layer 430, and the third barrier layer 440 may include different barrier materials selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof. As an example, the first barrier layer 420, the second barrier layer 430, and the third barrier layer 440 may be in the following order: SixNy / SixCy / SixOyNz.

[0073] In some embodiments, the second barrier layer 430 may be disposed or deposited directly on the first barrier layer 420. In some embodiments, the third barrier layer 440 may be disposed or deposited directly on the second barrier layer 430. In some embodiments, no other layers or films exist between the first barrier layer 420, the second barrier layer 430, and the third barrier layer 440.

[0074] According to some embodiments that can be combined with other embodiments described herein, the third barrier layer 440 may have a thickness equal to or less than 150 nm, in particular a thickness equal to or less than 130 nm, and more particularly a thickness equal to or less than 110 nm. In some embodiments, the third barrier layer 440 may have a thickness equal to or greater than 20 nm, in particular a thickness equal to or greater than 40 nm, and more particularly a thickness equal to or greater than 60 nm. In some embodiments, the third barrier layer 440 may have a thickness of 20 nm or more and 150 nm or less, in particular a thickness of 40 nm or more and 130 nm or less, and more particularly a thickness of 60 nm or more and 110 nm or less.

[0075] exist Figure 5 In the embodiment, the closure 500 for the pharmaceutical preparation is similar to Figure 4 The closure 400 for a pharmaceutical preparation is different in that at least one barrier layer 560 includes other barrier layers, such as a fourth barrier layer 550.

[0076] In addition, if Figure 5 , at least one barrier layer 560 may include an adhesion promoting layer 515, which is above the polymer closure body 510. In addition, at least one barrier layer 560 may include a first barrier layer 520, which is above the adhesion promoting layer 515. In addition, at least one barrier layer 560 may include a second barrier layer 530, which is above the first barrier layer 520. In addition, at least one barrier layer 560 may include a third barrier layer 540, which is above the second barrier layer 530. In addition, at least one barrier layer 560 may include a fourth barrier layer 550, which is above the third barrier layer 540. In this particular example, the adhesion promoting layer 515 may include an adhesion promoting layer material.

[0077] According to some embodiments that can be combined with other embodiments described herein, the fourth barrier layer 550 may include a barrier material. In addition, the first barrier layer 520, the second barrier layer 530, the third barrier layer 540 and / or the fourth barrier layer 550 may include different barrier materials selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof. As an example, the first barrier layer 520, the second barrier layer 530, the third barrier layer 540 and the fourth barrier layer 550 may be in the following order: SixNy / SixCy / SixOyNz / SixOyCz.

[0078] In some embodiments, the second barrier layer 530 may be disposed or deposited directly on the first barrier layer 520. In some embodiments, the third barrier layer 540 may be disposed or deposited directly on the second barrier layer 530. In some embodiments, the fourth barrier layer 550 may be disposed or deposited directly on the third barrier layer 540. In some embodiments, no other layers or films exist between the first barrier layer 520, the second barrier layer 530, the third barrier layer 540, and the fourth barrier layer 550.

[0079] According to some embodiments that can be combined with other embodiments described herein, the fourth barrier layer 550 may have a thickness equal to or less than 150 nm, particularly equal to or less than 130 nm, and more particularly equal to or less than 110 nm. In some embodiments, the fourth barrier layer 550 may have a thickness equal to or greater than 20 nm, particularly equal to or greater than 40 nm, and more particularly equal to or greater than 60 nm. In some embodiments, the fourth barrier layer 550 may have a thickness of 20 nm or more and 150 nm or less, particularly 40 nm or more and 130 nm or less, and more particularly 60 nm or more and 110 nm or less.

[0080] According to some embodiments that may be combined with other embodiments described herein, at least one barrier layer 560 may include a second barrier layer 530 above the first barrier layer 520; may specifically include the second barrier layer 530 above the first barrier layer 520 and a third barrier layer 540 above the second barrier layer 530; and may more specifically include the second barrier layer 530 above the first barrier layer 520, the third barrier layer 540 above the second barrier layer 530, and a fourth barrier layer 550 above the third barrier layer 540.

[0081] According to some embodiments, which can be combined with other embodiments described herein, the at least one barrier layer 560 can include other barrier layers, particularly a fifth barrier layer, more particularly a fifth barrier layer and a sixth barrier layer, above the fourth barrier layer 550. However, it should be understood that the present disclosure is not limited to six barrier layers, and any suitable number of barrier layers can be used for the at least one barrier layer 560.

[0082] According to one aspect of the present disclosure and as Figure 6 As shown, a method 600 for manufacturing a closure for a drug formulation is provided. The method 600 includes providing at least one polymer closure body (step 610). The method 600 further includes forming at least one barrier layer over the at least one polymer closure body (step 620).

[0083] Thus, forming at least one barrier layer above at least one polymer closure body comprises sequentially depositing an adhesion promoting layer material and depositing at least one barrier layer material. In addition, the adhesion promoting layer material comprises SiOxCy:H. In addition, the barrier layer material is selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2 and combinations thereof. In particular, the term "sequentially" together with the term "comprising" in the sentence "forming at least one barrier layer above at least one polymer closure body comprises sequentially depositing an adhesion promoting layer material and depositing at least one barrier layer material" can be understood as following a series of events in time (e.g., depositing an adhesion promoting layer material and then depositing at least one barrier layer material), without excluding other temporal sequences of events (e.g., depositing an adhesion promoting layer material and depositing at least one barrier layer material at the same time; for example, other sequences between depositing an adhesion promoting layer material and thereafter depositing at least one barrier layer material).

[0084] Due to the simplicity of depositing at least one barrier layer on the polymeric closure body, the method 600 of the present disclosure for manufacturing a closure for a pharmaceutical preparation allows for reducing production costs and reducing production time, and allows for adjusting the barrier properties of the closure for a pharmaceutical preparation by depositing other barrier layers with different barrier layer materials. In addition, the method 600 of the present disclosure for manufacturing a closure for a pharmaceutical preparation allows for forming at least one barrier layer over at least one polymeric closure body, even if the polymeric closure body has a three-dimensional shape or structure, in particular including portions of the surface of the polymeric closure body that are difficult to access.

[0085] In some embodiments, providing at least one polymeric closure body may include treating a surface of the at least one polymeric closure body (e.g., forming or depositing at least one barrier layer on the surface) by applying an electrical discharge (e.g., plasma, glow discharge, corona discharge, dielectric barrier discharge, or atmospheric pressure discharge), chemical pretreatment, or flame pretreatment in the presence of a suitable reactive or non-reactive atmosphere.

[0086] In some embodiments, forming at least one barrier layer, depositing an adhesion promoting layer material, and / or depositing at least one barrier layer material over at least one polymeric closure body may be performed by physical vapor deposition or chemical vapor deposition (eg, sputtering or evaporation).

[0087] According to some embodiments, depositing the adhesion promoting layer material may include depositing the adhesion promoting layer material above at least one polymer closure body. According to some embodiments, depositing the adhesion promoting layer material may include forming an adhesion promoting layer, in particular, above at least one polymer closure body. In some embodiments, depositing at least one barrier layer material may include depositing at least one barrier layer material above the adhesion promoting layer material. In some embodiments, depositing at least one barrier layer material may include depositing a first barrier layer material, in particular, above the adhesion promoting layer material and more particularly above the adhesion promoting layer. In some embodiments, depositing the first barrier layer material may include forming a first barrier layer.

[0088] In some embodiments, depositing at least one barrier layer may further include depositing a second barrier layer material, particularly over the first barrier layer material and more particularly over the first barrier layer. In some embodiments, depositing the second barrier layer material may include forming a second barrier layer. In some embodiments, depositing at least one barrier layer may further include depositing a third barrier layer material, particularly over the second barrier layer material and more particularly over the second barrier layer. In some embodiments, depositing the third barrier layer material may include forming a third barrier layer.

[0089] In some embodiments, depositing at least one barrier layer may further include depositing a fourth barrier layer material, particularly over the third barrier layer material and more particularly over the third barrier layer. In some embodiments, depositing the fourth barrier layer material may include forming a fourth barrier layer. In some embodiments, the first barrier layer material, the second barrier layer material, the third barrier layer material, and / or the fourth barrier layer material may include different barrier layer materials selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

[0090] In some embodiments, depositing the adhesion promoting layer material may include introducing at least one adhesion promoting layer precursor into the plasma. In some embodiments, depositing the first barrier layer material may include introducing at least one first barrier layer precursor into the plasma. In some embodiments, depositing the second barrier layer material may include introducing at least one second barrier layer precursor into the plasma.

[0091] In some embodiments, depositing the third barrier material may include introducing at least one third barrier material precursor into the plasma. In some embodiments, depositing the fourth barrier material may include introducing at least one fourth barrier material precursor into the plasma. Examples of the first barrier material precursor, the second barrier material precursor, the third barrier material precursor, and the fourth barrier material precursor may include silane, siloxane, hexamethyldisilazane (HMDSN), O2, N2O, NH3, aluminum chloride (AlCl3), trimethylaluminum (TMA), aluminum triisopropoxide (AIP), titanium isopropoxide (Ti{OCH(CH3)2}4), titanium butoxide (C 16 H 36 O4Ti), titanium(IV) acetylacetonate (Ti(C5H7O2)4). Examples of siloxanes are hexamethyldisiloxane (HMDSO), tetramethyldisiloxane (TMDSO), and tetraethylorthosilicate (TEOS).

[0092] In some embodiments, the first barrier layer material and the second barrier layer material may include different barrier layer materials selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof. In some embodiments, the first barrier layer material, the second barrier layer material, and the third barrier layer material may include different barrier layer materials selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof. In some embodiments, the first barrier layer material, the second barrier layer material, the third barrier layer material, and the fourth barrier layer material may include different barrier layer materials selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

[0093] According to some embodiments, the barrier layer material may include SiO2, and forming at least one barrier layer over at least one polymer closure body may further include simultaneously depositing an adhesion promoting layer material incrementally and at least one barrier layer material incrementally, in particular a first barrier layer material incrementally.

[0094] In some embodiments, the incremental deposition of the adhesion promoting layer material and the incremental deposition of at least one barrier layer material, in particular the incremental deposition of the first barrier layer material, can be performed by gradually modifying at least one plasma-related process parameter while depositing the adhesion promoting layer material and / or gradually changing the amount or chemical composition of at least one barrier layer material precursor, in particular the first barrier layer material precursor, while depositing the adhesion promoting layer material.

[0095] Examples of at least one barrier layer material precursor are silane, siloxane, hexamethyldisilazane (HMDSN), O2, N2O, NH3, aluminum chloride (AlCl3), trimethylaluminum (TMA), aluminum triisopropoxide (AIP), titanium isopropoxide (Ti{OCH(CH3)2}4), titanium butoxide (C 16 H 36 O4Ti), titanium (IV) acetylacetonate (Ti(C5H7O2)4). Examples of siloxanes are hexamethyldisiloxane (HMDSO), tetramethyldisiloxane (TMDSO) and tetraethylorthosilicate (TEOS). Thus, the decreasing deposition of the adhesion promoting layer material and the increasing deposition of at least one barrier layer material, in particular the increasing deposition of the first barrier layer material, can form a gradient chemical composition over the thickness of the first barrier layer.

[0096] In some embodiments, at least one plasma-related process parameter may include at least one parameter selected from the group consisting of: plasma power, carrier flow rate, temperature, bubbler flow rate, dilution flow rate, or vertical position of the plasma head relative to the polymer enclosure body. Examples of equipment that can be used for this are a classic bubbler or a hybrid volatile liquid delivery system.

[0097] Figure 7 and Figure 8 Schematic diagrams of spin deposition apparatuses 700 and 800 for manufacturing closures for pharmaceutical formulations are shown according to embodiments described herein.

[0098] The rotary deposition apparatus 700 and 800 for manufacturing a closure for a pharmaceutical preparation comprises a vacuum chamber 710, 810. In addition, the rotary deposition apparatus 700 and 800 comprises a rotary container 720, 820, which is located within the vacuum chamber 710, 810 and is configured to hold at least one polymer closure body inside. In addition, the rotary deposition apparatus 700 and 800 comprises at least one deposition source 730, 830a, 830b, which is connected to the vacuum chamber 710, 810.

[0099] In addition, at least one deposition source 730, 830a, 830b connected to the vacuum chamber 710, 810 is located outside the vacuum chamber 710, 810. Due to the location of the at least one deposition source 730, 830a, 830b, rapid cleaning, repair and replacement of parts of the at least one deposition source 730, 830a, 830b (for example, rapid cleaning of shielding and replacement of antenna tubes of the at least one deposition source 730, 830a, 830b) are possible.

[0100] In addition, at least one deposition source 730, 830a, 830b connected to the vacuum chamber 710, 810 is configured to form at least one barrier layer on at least one polymer enclosure body, for example, deposit an adhesion promoting layer material and / or deposit at least one barrier layer material. In addition, the rotating container 720, 820 includes a perforated wall, which is configured to allow the formation of at least one barrier layer on at least one polymer enclosure body, for example, depositing an adhesion promoting layer material on at least one polymer enclosure body and / or depositing at least one barrier layer material on at least one polymer enclosure body.

[0101] The spin deposition apparatus for manufacturing closures for pharmaceutical preparations of the present disclosure allows for manufacturing closures for pharmaceutical preparations on an industrial scale, ie in a high-volume manufacturing process and at a high productivity level.

[0102] like Figure 7 As shown in an exemplary manner in FIG. 7 , the rotary deposition apparatus 700 may include one deposition source 730 connected to the vacuum chamber 710. Therefore, the rotary deposition apparatus 700 including one deposition source 730 connected to the vacuum chamber 710 may form a gradient chemical composition over the thickness of the first barrier layer as described above, because it is possible to obtain such a gradient chemical composition using only one deposition source.

[0103] like Figure 8 As shown in an exemplary manner in FIG. 8 , the rotary deposition apparatus 800 may include two deposition sources 830a, 830b connected to the vacuum chamber 810. Therefore, the rotary deposition apparatus 800 including the two deposition sources 830a, 830b connected to the vacuum chamber 810 may form at least one barrier layer including more than one barrier layer material as described above.

[0104] In some embodiments, the perforated wall may be symmetrical relative to the axis of rotation of the rotating container 720, 820. In some embodiments, the rotating container 720, 820 may have a cylindrical shape, a spherical shape or a cubic shape. In some embodiments, the rotating container 720, 820 may be configured to rotate clockwise and / or counterclockwise. Since the rotary deposition apparatus includes a rotating container, the rotating container rotates a polymer closure body or a plurality of polymer closure bodies in the rotating container during the manufacture of the closure for the pharmaceutical preparation, so the deposition of at least one barrier layer above the polymer closure body is uniform over the entire polymer closure body. In addition, due to the combination of the rotating container and at least one deposition source, at least one barrier layer is deposited even on the most inaccessible part of the surface of the polymer closure body.

[0105] In some embodiments, the rotating container 720, 820 may be detachable. Therefore, the rotating container 720, 820 may be easily cleaned after a certain period of time. In some embodiments, at least one deposition source 730, 830a, 830b may include a high-density plasma chemical vapor deposition device, including an inductively coupled plasma device or a microwave induced plasma device.

[0106] Fig. 9 A schematic diagram of a rotating container 900 of a rotating deposition apparatus for manufacturing closures for pharmaceutical formulations is shown according to embodiments described herein.

[0107] In some embodiments, the perforated area of ​​the perforated wall 920 can be at least 75%, particularly at least 80%, and more particularly at least 85% relative to the non-perforated area of ​​the perforated wall 920. In some embodiments, the perforated wall 920 can include circular, triangular, or square through-holes 930.

[0108] While the foregoing is directed to embodiments of the present disclosure, other and further embodiments of the present disclosure may be devised without departing from the basic scope of the present disclosure, and the scope of the present disclosure is determined by the claims that follow.

Claims

1. A closure for a pharmaceutical preparation, the closure comprising: a polymer closure body; and at least one barrier layer, said at least one barrier layer being over said polymeric closure body, wherein the at least one barrier layer comprises: an adhesion promoting layer material within at least a portion of the thickness of the at least one barrier layer proximate to the surface of the polymer closure body, the adhesion promoting layer material comprising SiOxCy:H, and A barrier layer material, wherein the barrier layer material is within at least a portion of the thickness of the at least one barrier layer away from the surface of the polymer closure body, the barrier layer material being selected from the group consisting of: SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2, and combinations thereof.

2. A closure for a pharmaceutical formulation according to claim 1, wherein the barrier material comprises SiO2, and the at least one barrier layer comprises a first barrier layer above the polymeric closure body, the first barrier layer having a gradient chemical composition across the thickness of the first barrier layer, and the gradient chemical composition comprises: a first chemical composition corresponding to the adhesion promoting layer material within at least a portion of the thickness of the first barrier layer proximate a surface of the polymeric closure body, and A second chemical composition corresponding to the barrier layer material within at least a portion of the thickness of the first barrier layer distal from the surface of the polymeric closure body.

3. The closure for a pharmaceutical preparation according to claim 1, wherein the at least one barrier layer comprises: an adhesion promoting layer overlying the polymer closure body; and a first barrier layer, the first barrier layer being above the adhesion promoting layer, The adhesion promoting layer comprises the adhesion promoting layer material, and the first barrier layer comprises the barrier layer material.

4. A closure for pharmaceutical preparations according to any one of claims 2 and 3, wherein the at least one barrier layer further comprises a second barrier layer above the first barrier layer, in particular a second barrier layer above the first barrier layer and a third barrier layer above the second barrier layer, and more particularly a second barrier layer above the first barrier layer, a third barrier layer above the second barrier layer and a fourth barrier layer above the third barrier layer.

5. A closure for pharmaceutical preparations according to any one of the preceding claims, wherein the at least one barrier layer has a thickness equal to or less than 500 nm, in particular equal to or less than 480 nm and more in particular equal to or less than 460 nm; and / or the at least one barrier layer has a thickness equal to or greater than 120 nm, in particular equal to or greater than 140 nm and more in particular equal to or greater than 160 nm.

6. A closure for a pharmaceutical preparation according to any one of the preceding claims, wherein the at least one barrier layer has a thickness of less than 10 -1 g / m 2 / day water vapor transmission rate, especially less than 10 -2 g / m 2 / day water vapor transmission rate and more particularly 10 -3 g / m 2 / day water vapor transmission rate.

7. A closure for a pharmaceutical preparation according to any one of the preceding claims, wherein at least one barrier layer has a relative humidity of less than 10 -1 ml / m 2 / day oxygen transmission rate, especially less than 10 -2 ml / m 2 / day oxygen transmission rate and more particularly 10 -3 ml / m 2 / day oxygen transmission rate.

8. A closure for a pharmaceutical formulation according to any one of the preceding claims, wherein the polymeric closure body is a synthetic rubber closure body and the synthetic rubber closure body comprises at least one polymer selected from the group consisting of copolymers of styrene and butadiene, polyisoprene, halogenated copolymers of isobutylene and isoprene, such as bromobutyl rubber or chlorobutyl rubber, and combinations thereof.

9. A method for manufacturing a closure for a pharmaceutical preparation, the method comprising: providing at least one polymeric closure body; as well as forming at least one barrier layer over the at least one polymer closure body, Wherein forming at least one barrier layer above the at least one polymer closure body comprises sequentially depositing an adhesion promoting layer material and depositing at least one barrier layer material, wherein the adhesion promoting layer material comprises SiOxCy:H, and the barrier layer material is selected from the group consisting of SixNy, SixCy, SixOyNz, SixOyCz, SiO2, AlxOy, AlOxNy, TiO2 and combinations thereof.

10. A method for manufacturing a closure for a pharmaceutical formulation according to claim 9, wherein the barrier layer material comprises SiO2, and forming at least one barrier layer over the at least one polymer closure body further comprises simultaneously depositing the adhesion promoting layer material incrementally and depositing the at least one barrier layer material incrementally, in particular depositing the first barrier layer material incrementally.

11. The method for manufacturing a closure for a pharmaceutical preparation according to claim 10, wherein simultaneously depositing the adhesion promoting layer material incrementally and depositing the at least one barrier layer material incrementally, in particular depositing the first barrier layer material incrementally, comprises: gradually modifying at least one plasma-related process parameter while depositing the adhesion promoting layer material, and / or The amount or chemical composition of at least one barrier layer material precursor, in particular a first barrier layer material precursor, is gradually varied while depositing the adhesion promoting layer material.

12. A rotary deposition apparatus for manufacturing a closure for a pharmaceutical preparation, the rotary deposition apparatus comprising: Vacuum chamber; a rotating container located within the vacuum chamber and configured to retain at least one polymeric closure body therein; and at least one deposition source connected to the vacuum chamber, the at least one deposition source being located outside the vacuum chamber and configured to form at least one barrier layer on the at least one polymer enclosure body, Wherein the rotating container comprises a perforated wall configured to allow the at least one barrier layer to be formed on the at least one polymeric closure body.

13. The rotary deposition apparatus according to claim 12, wherein the perforated area of ​​the perforated wall relative to the non-perforated area of ​​the perforated wall is at least 75%, in particular at least 80%, more in particular at least 85%.

14. The rotary deposition apparatus according to any one of claims 12 and 13, wherein the perforated wall is centrally symmetric with respect to the axis of rotation of the rotary container.

15. The rotary deposition apparatus according to any one of claims 12 to 14, wherein the at least one deposition source comprises a high density plasma chemical vapor deposition apparatus comprising an inductively coupled plasma apparatus or a microwave induced plasma apparatus.

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