BR112016022189B1 - PACKAGING SYSTEM TO MAINTAIN THE PHYSICOCHEMICAL INTEGRITY OF THE CONTENT OF THE PACKAGING SYSTEM - Google Patents

Abstract

PACKAGING SYSTEM AND METHOD FOR INHIBITING THE ENTRY OF MOISTURE. The present invention relates to a packaging system for maintaining the physicochemical integrity of the contents of the packaging system which includes: an inner bag formed of a gas and/or moisture permeable material, an outer bag formed of an impermeable polymer material , a discharge opening providing access to the interior of the outer bag; and a desiccant or gas cleaning material. The first end of the outer bag sealingly surrounds the outer wall of the discharge opening. The second end of the inner bag is sealed shut, and the desiccant or gas cleaning material is disposed within an insulated compartment. The second end of the outer bag is sealed shut to isolate the interior from the environment outside the packaging system.

Description

[001] This application claims priority from Provisional Application Serial Number 61/971,003, filed March 27, 2014, which is incorporated herein in its entirety.

FIELD OF THE INVENTION

[002] The present invention is a packaging system that maintains the physicochemical integrity of its contents, free-flowing characteristics. Specifically, the present invention relates to packaging systems that prevent caking of salts used in the manufacture of biopharmaceuticals (e.g., in cell culture production).

BACKGROUND OF THE INVENTION

[003] Various salts and buffers are used in the manufacturing operations associated with the production of biopharmaceuticals (eg, cell culture production and protein purification). These chemicals are dissolved under sterile conditions to make up a variety of solutions. A common problem with supplying granular solids is that they have a tendency to clog (ie, stick together to form a mass) due to the presence of moisture in the solid. Moisture can come from two sources, externally and internally. Internal moisture is found on the surface of the salt and can be released when there are changes in temperature. External moisture enters the packaging system from the environment outside the packaging system. Solid caking is a major problem in the industry and attempts to solve this problem include adding anti-caking agents and changing the crystal size. However, none of these attempts completely solved the problem. The addition of anti-caking agents to packages containing salts is undesirable because anti-caking agents often include compounds that interfere with the pharmaceutical manufacturing process.

[004] Salts tend to stick together during storage due to migration of free moisture present on the surface of the salt or due to moisture migration from the external environment. The caking mechanism is the result of the formation of small salt bridges between the particles due to a partial dissolution of the contacted salt by the free moisture. Over time the bridges become stronger and when a sufficient amount of moisture is present the product can become a solid unusable mass. Temperature changes in the environment help to release free moisture onto the surfaces of these materials and caking increases the more the temperature changes.

[005] A packaging system that prevents salts from stoning is described in U.S. Patent. Number 6,102,198 to Mallinckrodt, which uses a moisture permeable bag to allow moisture to pass from the salts through the bag into desiccants placed around the bag - or at the bottom, top or sides of the bag. Any free moisture in the salts or that enters from the outside is trapped (ie, absorbed) by the desiccants. However, the system has some disadvantages; the drum is expensive and can be difficult for the user to empty. Therefore, there is a need for new packaging systems that can remove free moisture from their contents and prevent caking until the contents of the package have been completely consumed. The system must maintain uniformity of free-flowing material (free from clogging) through the drum/pack. The location of the desiccant must be selected so that it cannot migrate or depart and contaminate the product. The packaging system must also be designed to provide a direct supply of product into a reactor / mixing vessel through a port and allow spectroscopic analysis (Raman spectroscopy) of the product without opening the inner bag and risking product contamination. . In addition, the packaging system must prevent external moisture from passing water through the walls of the package into the package.

SUMMARY OF THE INVENTION

[006] In accordance with the present invention, a packaging system for inhibiting the ingress of moisture into the contents of the package and a continuous removal of any free moisture in the contents is provided. In a preferred embodiment, the packaging system has a first end and a second end and comprises, consists of or essentially consists of: an inner bag, an outer bag, a discharge opening, a pressure equalizing opening and at least one desiccant or gas cleaning material. The inner bag is formed of a gas and/or moisture permeable material and has an interior, a first end and a second end. The outer bag is formed of a gas and/or moisture impermeable polymeric material (e.g., HDPE, various LDPEs, and other similar polymeric materials) and has a first end and a second end. The outer bag is also transparent to facilitate rapid identification of the contents of the packaging system by Raman spectroscopy (eg a portable Raman spectrometer).

[007] The discharge opening has an outer wall that defines an inner passage that provides access to the interior of the outer bag. The pressure equalizing opening vents air from the interior of the inner bag when the inner bag is being filled and allows a filtered or inert gas to enter the interior when the inner bag is being emptied. The desiccant(s) or gas cleaning material may be a moisture or gas absorbing material that can be safely used with pharmaceuticals.

[008] The inner bag is formed from a layer of a gas and/or moisture permeable material and has a first end, a second end and opposite side edges. The side edges are sealed to the inner side wall of the outer bag of the second end of the outer bag. The first end of the inner bag is secured within the outer bag at an intermediate point to the first and second ends of the outer bag or to the outer wall of the discharge opening to form a second compartment. After the first end of the inner bag is sealed to the outer wall of the discharge opening, the first end of the outer bag sealingly surrounds the first end of the inner bag and the entire outer wall of the discharge opening to form an intermediate space (also referred to herein). as a first compartment) between the inner bag and the side wall of the outer bag. The outer bag may be comprised of two layers and preferably may be formed as a continuous layer for increased product strength by extruding the outer bag with a tube or sleeve.

[009] After the desiccant(s) and/or gas cleaning material are disposed inside the inner bag (also referred to herein as the second compartment), the second end of the inner bag is sealed shut. The lower end of the inner bag containing the desiccant material may be heat sealed or cast along a line extending horizontally and parallel to the second end of the inner bag. The heat seal is located at least 101.6 mm (4 inches) above the bottom opening, preferably a minimum of 127 mm (5 inches) from the bottom opening and more preferably 152.4 mm (6 inches) or more. The function of this seal is to keep the inner bag containing the desiccant away from the discharge opening so that it does not impede the flow of material during emptying operations. After the desiccant material is added to the inner bag, the second ends of the inner and outer bags are sealed shut to isolate the intermediate space from the outside environment for the packaging system. The HDPE coating does not include glidants or blocking agents; however, an anti-static agent can be added to the HDPE coating to ensure that all of the product is delivered and to prevent the product from sticking to walls due to static buildup.

[0010] In a second embodiment, the first end of the inner bag is sealingly secured to the outer wall of the discharge opening and the first end of the outer bag sealingly surrounds the first end of the inner bag and is sealingly secured around the outer wall of the opening. outlet to form an intermediate space (also referred to herein as a compartment or the second compartment) between the inner bag and the outer bag. The desiccant(s) and/or gas cleaning material are arranged in the interspace and the second end of the inner bag is sealed closed. The function of this seal at the lower end of the inner bag is to prevent the inner bag from falling to the bottom of the packaging system and preventing the flow of material through the discharge opening during emptying operations. The second end of the outer bag is then sealed shut to isolate the intermediate space (i.e., first compartment) from the environment outside the packaging system. The HDPE coating does not include a slip agent, or blocking agents, however an anti-static agent is added to the HDPE coating to ensure that all product is delivered and to prevent the product from sticking to walls due to static buildup.

[0011] The discharge opening is used to fill and discharge materials contained inside the inner bag. The first end of the HDPE outer bag forms a seal around the outer wall of the discharge opening. The discharge opening is located at the bottom of the packaging system in the HDPE outer bag. The discharge opening may have a removable cover to close and seal the discharge opening. The removable lid isolates the contents of the packaging system from the outside environment during transport and storage. The packaging system may also include a handle attached to the second end of the packaging system to facilitate user manipulation of the packaging system.

[0012] The pressure equalization opening is located near the second end of the packaging system and has a passageway that extends between the interior of the inner bag and the environment external to the packaging system. The pressure equalizing port passage contains one or more filter materials that contain at least one desiccant and/or gas cleaning materials, which can selectively prevent moisture or certain gases from entering the interior of the inner bag. The pressure equalizing opening may also facilitate the introduction of dry inert gas to coat the material within the inner bag.

[0013] The gas permeable material of the inner bag is preferably formed of continuous, very fine fibers of randomly distributed and non-directional high-density polyethylene. The gas impermeable material of the outer bag preferably includes a low density or high density polyethylene. The gas impermeable material may include at least three layers with an inner layer formed of a gas barrier material. In a preferred embodiment, the gas barrier material of the inner layer is an ethylene/vinyl alcohol copolymer or polychlorotrifluoroethylene.

[0014] In another embodiment, the packaging system has a first end and a second end and comprises, consists of or essentially consists of: a first plastic layer, a second plastic layer, a layer of permeable material disposed between the first and second plastic layers, a discharge port, a pressure equalizing port and at least one desiccant or gas cleaning material. The first and second plastic layers are preferably made of a substantially gas impermeable plastic, more preferably of HDPE and/or LLDPE, and at least one of the layers is transparent. The permeable inner layer is preferably made of an ethylene/vinyl alcohol copolymer or polychlorotrifluoroethylene. The three layers are of substantially the same dimensions and the outer edges are aligned and sealed by a well known method (e.g. heat stamping or ultrasonic welding) to form a bag with a first and second compartment separated by the gas permeable layer.

[0015] The first end of the packaging system is attached to the handle and the pressure equalization opening is located in the first plastic layer near the first end. The discharge opening is located in the first plastic layer near the second end. The first compartment is arranged between the first plastic layer and the permeable layer and contains contents such as salts used in the manufacture of biopharmaceuticals. The desiccant and/or gas cleaning agent(s) are located within the second compartment between the second plastic layer and the gas permeable layer. The second compartment is segregated from the first compartment so that the desiccant and/or cleaning agents are isolated from the contents so that they do not unintentionally leak out with the contents of the first compartment. The pressure equalization opening vents air from the interior of the first compartment when it is being filled and allows a filtered or inert gas to enter the interior when the first compartment is being emptied. Optionally, an opening may be located in the second plastic layer for adding and removing desiccants and/or gas cleaning agents.

[0016] For a long-term storage of the packaging system with the product inside the inner bag, an overstuff is placed over the primary bag and heat-sealed closed. The overhang serves as a moisture barrier and further insulates the product within the packaging system from moisture. The overstuff can be composed of a Mylar®-like material (ie the polyester layer or polyethylene terephthalate (PET) film) that has a very low moisture transmission rate.

BRIEF DESCRIPTION OF THE FIGURES

[0017] Preferred embodiments of the packaging system of the present invention, as well as other objects, features and advantages of this invention, will be apparent from the accompanying drawings in which:

[0018] Figure 1 is a side view of a first embodiment of the packaging system of the present invention.

[0019] Figure 2 is a side view of the embodiment of the packaging system in Figure 1 showing the outer bag and the inner bag.

[0020] Figure 3 is a side view of the embodiment of the packaging system in Figure 1 showing the inner and outer bag.

[0021] Figure 4 is a side view of the embodiment of the packaging system in Figure 1 showing the outer bag with a transparent panel and a window for viewing the contents.

[0022] Figure 5 is a perspective view of the pressure equalization opening and filter system of the packaging system shown in Figure 1.

[0023] Figure 6 is a perspective view of the cover and lock ring for the pressure equalization opening shown in Figure 5.

[0024] Figure 7 is a top view of the snap ring for the pressure equalization opening shown in Figure 5.

[0025] Figure 8 is a side view of the embodiment of the packaging system in Figure 1 showing the handle.

[0026] Figure 9 is a side view of the second embodiment of the packaging system which has two compartments separated by a gas permeable layer secured in the discharge opening.

[0027] Figure 10 is a front view of the packaging system shown in Figure 9 with the handle removed to show the relationship of the three layers that make up the packaging system.

[0028] Figure 11 is a front view of the packaging system shown in Figure 9 enclosed within a pouch.

[0029] Figure 12 is a photograph of the packaging system after testing in a stability chamber.

[0030] Figure 13 is a photograph of a prior art packaging system after testing in a stability chamber.

DETAILED DESCRIPTION OF THE INVENTION

[0031] The present invention is a packaging system that reduces caking of products contained in the packaging system, preferably salts, due to moisture. The package uses a moisture barrier film that prevents external moisture from migrating through the walls of the package and into the inside of the package. Clogging is prevented by removing excess water that covers all particles when they are packed in a bulk pack. The packaging system removes excess moisture in the crystals. In one embodiment, the packaging system includes a gas, vapor, and/or moisture permeable inner bag that contains the product and an outer moisture and/or gas impermeable bag that closes the inner bag and creates an intermediate space between the bag. inner and outer bag. The key to preventing product clogging due to moisture keeping the inner bag at the correct moisture and gas level is to capture any moisture or free gas that may be released by the product (e.g. salts) as a result of temperature changes in the environment. . Moisture is uniformly removed from the product formed into the inner bag using a gas permeable material that transmits moisture (i.e. water vapor) through the wall of the bag into the interspace. The interspace contains materials that absorb moisture, oxygen and/or selected gases (eg HCl). Space can also be filled with an inert gas.

[0032] As used herein, the term "outer bag" refers to the closed structure formed by the outer, impermeable walls of the packaging system. The term is used interchangeably with the term "first compartment".

[0033] As used herein, the term "inner bag" refers to the closed structure within the outer bag of the packaging system that has at least one wall formed of a permeable material and receives the desiccant. The term is used interchangeably with the term "second compartment".

[0034] As used herein, the term "layer" refers to one or more layers of polymeric material that are formed into a single layer structure. The layers can be formed from the same polymer or different polymers. With reference to the permeable layer, the layer or layers may be formed from a polymer or from a woven fabric or synthetic material.

[0035] As used herein, the term "impermeable" refers to a material through which substances, such as liquids or gases, cannot pass or can only pass in very small amounts.

[0036] As used herein, the term "permeable" refers to a material through which substances, such as liquids or gases, can freely pass but substantially prevent the passage of solid materials.

[0037] As used herein, the term "desiccant" refers to a hygroscopic substance that induces or sustains a state of dryness (desiccation) in its vicinity. Desiccants are preferably prepackaged solids that absorb water. In preferred embodiments, the desiccant material is clay, molecular sieves, or silica.

[0038] As used herein, the term "unit" refers to an amount of desiccant, which will absorb a certain percentage of its weight at certain moisture levels. For this description, one "unit" is approximately equal to 28.35 grams (one ounce).

[0039] As used herein, the term "fused" or "fusion" refers to a method of sealing two or more layers of polymeric materials together by applying heat at a temperature above the higher melting point of the two or more polymeric materials. . Ultrasonic welding is a fusion method. When the two or more layers of polymeric materials cool, they are sealed together in the areas where heat has been applied.

[0040] The packaging system must also protect the product and maintain the integrity of the product, for example, by keeping the product sterile, dry, and free of lumps. In addition, some materials are sensitive to oxygen and need to be kept in an inert oxygen-free environment. Another feature of the packaging system is that the product can be supplied directly into the reactor system without contacting the external environment and affecting the integrity of the product. This is preferably accomplished using a discharge port at one end of the packaging system, preferably approximately 101.6 mm (4 inches) in diameter, and a pressure equalizing port located at the other end of the packaging system. The pressure equalization opening allows filtered air or an inert gas to enter the packaging system as product is removed to prevent a vacuum from forming and ensure a continuous flow of product.

[0041] In a preferred embodiment, the packaging system has an inner bag surrounded by an outer bag. The inner bag has a first end which is connected to a discharge opening and an inner wall formed of a gas permeable material which extends from the discharge opening to a sealed second end. The first end of the outer bag is joined to the first end of the inner bag around the discharge opening and a surrounding outer wall extends coextensively with the inner wall to form an intermediate space around the inner bag. A desiccant or other moisture absorbing material (gas or oxygen absorbing materials may also be added) is placed into the interspace and then the second end of the outer bag is sealed over the second end of the inner bag. The second end of the packaging system (ie, the second ends of the inner and outer bags) may be attached to a handle which can be used to carry, hang or secure the packaging system and its contents during use or storage.

[0042] A pressure equalizing opening may be located near the second end of the packaging system to provide a passage between the interior of the inner bag and the external environment. The pressure equalizing port may be connected to a source of inert gas, such as nitrogen, at a low pressure to maintain an "inert gas blanket" between the contents of the inner bag and the external environment. Alternatively, the pressure equalizing port can be connected to a filter system that allows the interior of the inner bag to "breathe" air from the outside environment. The filter system may be formed of a cylindrical tube and may contain one or more filters that filter out moisture, oxygen and/or other gases that could potentially contaminate the product within the packaging system. Preferably, the filter material includes at least one desiccant or gas cleaning material. The end of the filter opposite the pressure equalizing opening may be sealed with a locking cap, which is used when the packaging system is being shipped or stored. When the contents of the packaging system are being removed through the discharge opening, the cover on the filter system is removed so that outside air can enter the filter system and pass through the pressure equalization opening to facilitate delivery of the packaging system content.

[0043] The packaging system includes an inner bag formed from a layer of porous, moisture-permeable material, such as a fabric or Tyvek®, and an outer bag formed from a non-porous layer, for example, any of several different polyethylenes. The layer of porous material allows water vapor to pass through in order to prevent moisture from accumulating inside the inner bag that contains the product. Fabric is typically produced by weaving or knitting textile fibers, such as wool, cotton or a fiber or yarn made from polymeric materials. Tyvek® is the preferred material for the porous layer and is manufactured by E.I. Du Pont De Nemours and Company, Wilmington Delaware. Tyvek® is formed using continuous, very fine fibers of high density polyethylene, preferably 100 percent high density polyethylene, which are randomly distributed and non-directional. These fibers are first spun at high speed, then laid as a sheet on a moving bed before being bonded together by heat and pressure - without the use of binders, sizers or fillers. By varying both the deposition rate and bonding conditions the high speed spun layer can be manufactured to form soft structured or hard structured Tyvek®.

[0044] A portion of the inner bag wall may be transparent so that the contents of the inner bag can be seen through the transparent or semi-transparent outer bag wall. The transparent portion of the inner bag wall need not be gas permeable and may be formed by a panel or a window. Such windows or panels are commonly used in the packaging industry so that the contents can be seen and one skilled in the art would be familiar with the methods used to form such transparent portions.

[0045] The packaging system has an outer bag with an outer bag structure, also referred to here as the outer film structure. Specifically, the present invention relates to outer film structures made from polyethylene copolymers; although polypropylene films can also be used. For the purposes of this description, the terms "polyethylene film" or "polyethylene layer" are intended to include any of the types of polyethylene that are described below, as well as multilayer films that contain two or more types of polyethylene, for example, a layer of high density polyethylene and a layer of low density polyethylene.

[0046] Polyethylene is the name for a polymer whose basic structure is characterized by the chain --CH2 CH2)n. Polyethylene homopolymer is generally described as being a solid which has a partially amorphous phase and a partially crystalline phase with a density between 0.915 to 0.970 g/cm 3 . The relative crystallinity of polyethylene is known to affect its physical properties. The amorphous phase imparts flexibility and high impact strength while the crystalline phase imparts a high softening temperature and stiffness.

[0047] Unsubstituted polyethylene is generally referred to as high density homopolymer and has a crystallinity of 70 to 90 percent with a density of between approximately 0.96 to 0.97 g/cm 3 . The most commercially used polyethylenes are not unsubstituted homopolymers but instead have C2 -C8 alkyl groups attached to the backbone. These substituted polyethylenes are also known as branched-chain polyethylenes. Also, commercially available polyethylenes often include other substituent groups produced by copolymerization. Branching with alkyl groups generally reduces crystallinity, density and melting point. Polyethylene density is recognized to be closely connected to crystallinity. The physical properties of commercially available polyethylenes are also affected by average molecular weight and molecular weight distribution, branch length and types of substituents.

[0048] One skilled in the art generally refers to several broad categories of polymers and copolymers as "polyethylene". The placement of a specific polymer in one of these "polyethylene" categories is often based on the density of the "polyethylene" and often by additional reference to the process by which it was made as the process often determines the degree of branching, crystallinity and density. In general, the nomenclature used is not specific to a compound but rather refers to a range of compositions. This range often includes both homopolymers and copolymers.

[0049] For example, "high density" polyethylene (HDPE) is commonly used in the art to refer to both (a) homopolymers of densities between approximately 0.960 to 0.970 g/cm3 and (b) copolymers of ethylene and an alpha-olefin (usually 1-butene or 1-hexene), which have densities between 0.940 and 0.958 g/cm 3 . HDPE includes polymers made with Ziegler or Phillips type catalysts and is also said to include high molecular weight "polyethylenes". In contrast HDPE, whose polymer chain has some branching, are "ultra high molecular weight polyethylenes" which are essentially unbranched especially polymers that have a much higher molecular weight than high molecular weight HDPE.

[0050] Hereinafter, the term "polyethylene" will be used (unless otherwise indicated) to refer to ethylene homopolymers as well as copolymers of ethylene with alpha-olefins and the term will be used without regard to the presence or absence of substituent branching groups.

[0051] Another broad grouping of polyethylene is "low density, high pressure polyethylene" (LDPE). The polyethylene industry began in the 1930s as a result of the discovery of a commercial process to produce LDPE by researchers at Imperial Chemical Industries, Ltd. LDPE is used to name branched homopolymers that have densities between 0.915 and 0.930 g/cm3 as well as copolymers that contain polar groups resulting from copolymerization, for example with vinyl acetate or ethyl acrylate. LDPEs typically contain long branches off the main chain (often called "backbone") with alkyl substituents of 2 to 8 carbon atoms.

[0052] In the 1970s, a new group of polyethylene was commercialized -- Linear Low Density Polyethylene (LLDPE). Only copolymers of ethylene with alpha olefins are in this group, LLDPEs are presently recognized by those skilled in the art as having densities of 0.915 to 0.940 g/cm 3 . The alpha-olefin used is usually 1-butene, 1-hexene, or 1-octene and Ziegler-type catalysts are usually employed (although Phillips catalysts are also used to produce LLDPE that have densities at the higher end of the range).

[0053] In the 1980s, yet another group of polyethylene came to prominence -- Very Low Density Polyethylene (VLDPE), which is also called "Ultra Low Density Polyethylene" (ULDPE). This grouping like the LLDPEs comprises only copolymers of ethylene with alpha-olefins, usually 1-butene, 1-hexene or 1-octene and are recognized by those skilled in the art as having a degree of structure linearity with short branches rather than long branches. characteristic side branches of LDPE. However, VLDPEs have lower densities than LLDPEs. The densities of VLDPEs are recognized by those skilled in the art to range between 0.860 and 0.915 g/cm 3 .

[0054] Various types of polyethylene resins have long been used to produce films that have different properties. These polyethylenes have been used alone, in blends and with copolymers in both monolayer and multilayer films for packaging applications for such food products. In the food industry, greater use of centralized food processing in conjunction with increased handling and long-distance transport has increased the demand for packaging films that have superior properties.

[0055] In the packaging industry, films are known to use coextruded, extrusion coated or laminated films which use such compositions as LLDPE, nylon, polyester, vinylidene chloride copolymer (PVDC), ethylene vinyl acetate copolymer (EVA) ) and ionomers.

[0056] It is generally known that the selection of films for pharmaceutical packaging includes consideration of one or more criteria such as puncture resistance, cost, sealability, rigidity, strength, printability, durability, barrier properties, machinability, optical properties such as haze and gloss, flex-crack strength and government approval for contact with pharmaceuticals. The type of polyethylene selected for use in the present invention and the thickness of the film (or layer for a multilayer film) will depend on these considerations, as will the size of the inner and outer bags and the estimated weight of the product.

[0057] The outer bag is made of a plastic film which may be transparent or semi-transparent and may have one or more layers formed by well-known extrusion, co-extrusion and/or lamination processes. Preferably, at least one of the film layers is a structural layer and includes polyethylene, more preferably high or low density polyethylene. The structural layer(s) are intended to provide strength and impact resistance, to support the articles within the inner bag and to prevent the outer bag from breaking. When the film includes multiple layers, the film may have a gas barrier layer that prevents oxygen from passing through the film. The preferred construction for a multilayer film includes a gas barrier layer disposed between two structural layers of polyethylene. The gas barrier layer can be made of ethylene/vinyl alcohol copolymer (EVOH) and polychlorotrifluoroethylene (PCTFE or PTFCE). Other materials used in gas barrier layers of films for the food industry may also be used and are well known to those skilled in the art.

[0058] Multilayer films may also have one or more ethylene polymer-based adhesive layers disposed between the gas barrier layer and the outer structural layers. In addition, the outer bag structure may have an outer heat seal layer that includes an ethylene copolymer, such as ethylene vinyl acetate copolymer, for bonding opposite sides of the outer bag together and for bonding the inner bag to the bag. external.

[0059] The inner and outer bags are joined together along the edges on at least three sides by a fusion bond. The fusion bond may be formed by ultrasonic welding of the layers to each other at their registered edges using a Branson ultrasonic welder (Branson Products, Inc., Danbury, Conn.) or other suitable ultrasonic welding tool. The bonded layers of the inner bag and the outer bag are joined at their edges on three sides to define an inner volume enclosed within the inner bag for containing an article of product therein, for example, a pharmaceutical product and an intermediate space between the inner bag. inner bag and outer bag and one side open. The interspace may contain a desiccant to absorb moisture or other materials to absorb oxygen, carbon dioxide or other gases that may be discharged by the product contained in the inner bag.

[0060] After the inner and outer bags are formed with the first ends connected at the discharge opening and the inner and outer bags defining an intermediate space, a desiccant or oxygen cleaning agent, such as sodium sulfite (Na2SO3), can be placed within the intervening space. The inner and outer bags are then sealed at the second ends to isolate the in-between space from the outside environment. However, the gas permeable wall of the inner bag allows gases and water vapor to pass from the interior of the inner bag into the space between. Thus, the intermediate space is isolated from gases in the external environment but is accessible to any gases that may form inside the inner bag.

[0061] The packaging system is now described with reference to the accompanying drawings, Figures 1-8, to further describe the features. Figure 1 shows the packaging system 10 which includes: an inner bag 12, an outer bag 14 with an intermediate compartment or space 13 therebetween, a discharge opening 16 with a lid 18 and a locking ring 20 and a handle 22 A desiccant 24 is disposed within the interspace 13 between the inner and outer bags 12, 14. Also shown is a pressure equalizing opening 26 connected to a filter system 28 with a lid 30 and a locking ring 32.

[0062] Figure 2 shows a side view of the packaging system 10 in which the bottom of the inner bag 12 is attached to the inner surface of the outer bag 14 intermediate the first and second ends of the outer bag 14. Preferably the point where the bottom of the inner bag 12 attaches to the inner surface of the outer bag 14 is at least 101.6 mm (4 inches) from the discharge opening 16, more preferably 127 mm (5 inches) and even more preferably 152.4 mm (6 inches). inches) or more. Figure 3 shows the inner bag 12 with the lower end secured inside the outer bag 14 and the other end open. Between the inner and outer bags 12, 14 is the intermediate space 13 which receives the desiccant 24 (Figure 1) and any gas cleaning materials. Figure 4 is similar to Figure 3 and this shows an embodiment in which the inner bag 12 is formed by a section 12a of gas permeable material, a panel 12b and a window 12c. Typically, the gas permeable material that forms the inner bag 12 is non-transparent and prevents the contents from being seen through the transparent outer bag 14. The panel 12b and window 12c are transparent and may be formed from materials that are not permeable to the air. gas. Methods for forming transparent openings in otherwise non-transparent plastic bags are well known to those skilled in the art.

[0063] Figure 5 shows the pressure equalizing port 26 and the filter system 28. The filter system 28 may include one or more desiccants and/or gas cleaning filter materials 34, 36, 38 that filter out moisture. and unwanted gases to prevent them from entering the interior of the inner bag 12. The lid 30 and the locking ring 32 as shown in Figures 6 and 7 are attached to the filter system 28 when the packaging system 10 is transported or stored. Figure 8 shows the handle that is attached to the packaging system 10 opposite the discharge opening 16 (Figure 1).

[0064] Figures 9 and 10 show a second embodiment of the packaging system 110 that includes: a first outer plastic layer 112 and second outer plastic layer 114 disposed on each side of a gas and moisture permeable layer 115 to form a first compartment 111 and a second compartment 115. Handle 122 is attached to the first end and a discharge opening 116 is located near the second end. One or more desiccant packs 124 are disposed within the second compartment 113 between the gas permeable layer 115 and the second plastic layer 114. Also shown is a pressure equalizing opening 126 connected to a filter system 128. gas 115 separates desiccant 124 from product 125 within packaging system 110 but allows moisture and gases to pass through.

[0065] Figure 11 shows an embodiment similar to the second embodiment shown in Figures 9 and 10 in which the bag system 110 includes an overhang 150. The outer bag 112 is placed within the overhang 150 for additional protection from gas and/or moisture. contaminating the contents of the outer bag 112 and for physical protection from damage that may occur during transport. overhang 150 may be made of Mylar® or a polymer material such as LDPE or HDPE. A seal 152 on top of the overhang 150 isolates the contents from the external environment.

EXAMPLES EXAMPLE 1

[0066] A model test bag was produced by heat sealing a multilayer bag, which included an inner layer made of Tyvek® that provides a vapor transmission wall disposed between two outer layers made of substantially gas impermeable HDPE and moisture. The top edges of the three layers were register-aligned and the inner Tyvek® layer extended to a point midway between the first and second ends of the two outer layers. The bottom and two side perimeter edges of the outer HDPE layers were sealed together to form a first compartment and the perimeter edges over the bottom and two sides of the Tyvek ® layer were sealed to the outer first HDPE layer to form a second compartment. One kg of the test salt was placed inside the first compartment at the top end of the bag on one side of the Tyvek® layer and the desiccant material was placed on the other side (five 1/6 Desicare clay type desiccants) of the Tyvek® layer. inside the second compartment. The perimeter edges of the three layers on the top side of the bag were sealed to close the system and isolate the product on one side of the Tyvek® wall from the desiccant on the other side so that the test salt was in contact with the water transmission wall. steam. Model salts such as sodium acetate trihydrate, sodium chloride, potassium nitrate, dextrose and mannitol were placed in individual bags. The bags were monitored and after 90 days it was determined that the packaging system prevents the test salts from stoning.

EXAMPLE 2

[0067] A laboratory study was performed to demonstrate the ability of the packaging system to maintain materials in a free-flowing state. In addition, tests were performed to compare the packaging system with a prior art single use bag. The new packaging system bag was filled with 11.3 kg of free flowing sodium chloride and the end cap, clip and clip were placed over the bag. Another standard single-use bag without the desiccant compartment (ie Flowmor™ technology) was filled with the same amount of free-flowing sodium chloride and sealed in the same way. Both bags were placed side by side inside a stability chamber at 40°C and 75% RH. Both bags were tested after 32 days; the sodium chloride inside the packaging system (see photograph in Figure 12) was free flowing and free of caking. The material inside the prior art bag (see photograph in Figure 13) was stoned and not free flowing.

EXAMPLE 3

[0068] Studies were performed under conditions of high humidity (40°C, 90% RH) in the bags to study the rates of infusion of moisture into the bag wall. A bag was placed inside the stability chamber with eight units of heavy desiccant (approximately 226.8 grams (8 oz)); the lid and clip were placed over the bag and sealed. The desiccant, after 96 hours, gained 6.5 grams of water, which showed that the desiccant would be used in up to 30 days in its water vapor transmission rate. The bag was then placed inside a Mylar® bag (or any suitable bag with a low moisture vapor transmission rate) and heat sealed. The vapor transmission rate was significantly increased and test results showed an expected shelf life of over 400 days.

EXAMPLE 4

[0069] The purpose of this study was to test the ability of the bags to deliver a cohesive powder that has flow characteristics in small amounts. The first test material was L-Glutamine; 240.0 g of material was added to the bag. The bag was sealed with an end cap, clip, and clip. The powder was then supplied to a heavy container. The amount supplied was 238.0 g, giving 99% material recovery. The study was repeated with a large amount of material, 9.1 kg of sodium chloride, recovered 9.1 kg close to 100% recovery.

[0070] Thus, while preferred embodiments of the present invention have been described, those skilled in the art will appreciate that other embodiments may be made without departing from the spirit of the invention, and it is intended to include all such additional modifications and changes as come within true scope of the claims presented herein.

Claims (18)

1. Packaging system (10) for maintaining the physicochemical integrity of the contents of the packaging system (10), the packaging system (10) having a first end and a second end, comprising: an outer bag (14) having a first compartment (13) and formed of a polymer material impermeable to gas and/or moisture, and having an interior, a side wall, a first end and a second end; a discharge opening (16) having an outer wall defining an inner passage, wherein the inner passage provides access to the interior of the outer bag (14); a pressure equalizing opening (26) located proximate the second end of the packaging system (10) and having a passageway extending between the interior of the outer bag (14) and the external environment of the packaging system (10), and wherein the pressure equalizing opening passage (26) contains one or more filter materials (28) comprising at least one desiccant or gas cleaning material; an inner bag (12) formed of a layer of a material permeable to gas and/or moisture and having a first end, a second end and opposing side edges, the side edges being sealed to the side wall inside the bag outer bag (14) of the second end of the outer bag (14), and wherein the first end of the inner bag (12) is secured within the outer bag (14) at a point midway between the first and second ends of the outer bag (14) ) or on the outer wall of the discharge opening (16) to form a second compartment; and at least one desiccant or gas cleaning material; characterized in that: the first end of the outer bag (14) is sealed around the outer wall of the discharge opening (16), wherein the at least one desiccant or gas cleaning material is disposed within the inner bag (12) and the second end of the inner bag (12) is sealed closed, wherein the second end of the outer bag (14) is sealed closed to isolate the interior from an environment external to the packaging system (10). 2. Packaging system (10) according to claim 1, characterized in that it still comprises a handle attached to the second end of the packaging system (10). 3. Packaging system (10) according to claim 1, characterized in that the layer of material permeable to gas and/or moisture is formed of continuous and very fine fibers of high density polyethylene randomly distributed and non-directional. 4. Packaging system (10) according to claim 1, characterized in that the gas and/or moisture impermeable material of the outer bag (14) comprises a low-density or high-density polyethylene. 5. Packaging system (10) according to claim 4, characterized in that the gas impermeable material comprises at least three layers with an intermediate layer formed from a gas barrier material. 6. Packaging system (10) according to claim 5, characterized in that the gas barrier material of the intermediate layer is an ethylene/vinyl alcohol copolymer or polychlorotrifluoroethylene. 7. Packaging system (10) according to claim 1, characterized in that the discharge opening (16) has a removable cover to close the discharge opening (16) and sealingly insulate the interior of the outer bag (14) from the external environment. 8. Packaging system (10) according to claim 1, characterized in that the side edges of the inner bag (12) are fused to the side wall inside the outer bag (14). 9. Packaging system (10) according to claim 1, characterized in that it further comprises an overhang having an outer wall comprising a gas and/or moisture impermeable material, a first open end, a sealed second end and an inner, wherein the outer bag (14) is placed into the overcrow through the first end and the first end of the overcrow is sealed. 10. Packaging system (10) according to claim 9, characterized in that the overstuff comprises two or more layers and one of the two or more layers is a gas and/or moisture barrier layer. 11. Packaging system (10) according to claim 1, characterized in that the inner bag (12) has a perimeter edge that extends along the first end, the second end and two or more sides that are contiguous to the first and second ends, wherein the outer bag (14) has a perimeter edge that extends along the first end, the second end and two or more sides that adjoin the first and second ends, wherein the perimeter edge along the along at least one of the first or second ends or one of the adjoining sides of the inner bag (12) is fused at the perimeter edge along at least one of the first or second ends or one of the adjoining sides of the outer bag (14). 12. Packaging system (10) according to claim 1, characterized in that the desiccant clay, molecular sieves or silica, and wherein the ratio of desiccant to contents of the packaging system (10) is at least 0, 4 units of desiccant per kilogram of content. 13. Packaging system (10) according to claim 1, characterized in that the inner bag (12) is made of a fabric or a layer formed using continuous and very fine fibers of high density polyethylene that are randomly distributed and non-directional. 14. Packaging system (10) according to claim 1, characterized in that the packaged material includes inorganic salts, organic compounds, amino acids and buffering materials. 15. Packaging system (10) according to claim 1, characterized in that the side wall is in the form of a tube or first and second sheets, wherein the tube has a continuous outer side wall, wherein the first and the second sheets have perimetric edges, wherein the perimetric edges are in registration and sealingly secured, and wherein the outer bag (14) has first and second ends and inner and outer surfaces. 16. Packaging system (10) according to claim 15, characterized in that the side wall comprises multiple layers of polymeric material. 17. Packaging system (10) according to claim 16, characterized in that at least one multi-layer layer is a moisture barrier layer. 18. Packaging system (10) according to claim 15, characterized in that the side wall comprises a low-density or high-density polyethylene, and the gas and/or moisture permeable layer is formed of continuous fibers and very thin, randomly distributed, non-directional, high-density polyethylene or fabric.

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