MXPA00004522A - Flexible medical container with selectively enlargeable compartments and method for making same - Google Patents

Abstract

A flexible container (10) is provided for the storage, and administration of medical solutions. The container incorporates a transparent front sheet (12) made from a planar layer of a polymer, and an opposing rear sheet (14). The rear sheet is made from a planar laminate layer. The front, and rear sheets are sealed together along a common peripheral edge (16) to form a volume enclosure (17). The volume enclosure is constructed of materials having high oxygen, and moisture barrier properties which allows the container thermoplastic to be stored for extended periods of time without degrading the contents. The volume enclosure is then inflated with a pressurized gas to permanently stretch the front, and the rear sheets outwardly, and to thereby increase the volume capacity of the container. An alternative embodiment of the container incorporates multiple compartments (22, 23, 24) separated by peeled seals (25, 26) for containing a diluent, and a medicament. The seals are ruptured by manipulations of the container to thereby mix the contents together for delivery through standard IV arrangement to a patient.

Description

FLEXIBLE MEDICINAL CONTAINER WITH SELECTIVELY AGGRANDABLE COMPARTMENTS AND METHOD FOR ITS MANUFACTURE FIELD OF THE INVENTION The present invention relates to flexible sterile containers for storing and administering medical solutions in a sterile environment. More particularly, the present invention relates to flexible medical containers for storing and administering IV solutions and having sides that are permanently stretched to enlarge their storage capacity.

BACKGROUND OF THE INVENTION Usually, sterile containers, various medical solutions are administered intravenously (via IV) to patients. These solutions can include any medical type fluid, such as body fluids and even solutions containing a drug (drug). Common packaging for storage and administration of these solutions includes flexible containers that have a compartment for storing the solution. A port of REF .: 120039 outlet connection is coupled to the compartment for administration and delivery of the solution to the patient through a conventional IV configuration.

Frequently, medical solutions consist of a mixed combination of a liquid diluent, for example, an aqueous solution of dextrose or NaCl, and a liquid medicament. Desirably, the medicament and the diluent are stored separately in the container under aseptic conditions and are not mixed until immediately before use in order to prevent degradation of the final product. The packaging of the diluent and the medicine is usually further complicated by the nature of the drug which may be in liquid form, therefore, being susceptible to hydraulic pressure in the container, as well as degradation under exposure to light or oxygen.

Accordingly, several of these medications that become unstable over time in the solution are typically stored separately in jars, gas-tight containers, or whatever resembles them before use. Before being administered to a patient, medications stored in this manner must be mixed, or diluted in, physiological solutions and diluents are also preserved separately. While the sterility and effectiveness of the medicament can be maintained, separate storage in components is cumbersome and involves the risk of bacteriological contamination during handling, mixing, and subsequent administration to the patient. Accordingly, they have been developed with medicinal containers that include compartments for storing unstable drugs and compartments containing diluting fluids. Immediately before IV administration to the patient, the components are placed in communication with each other so that the contents can be mixed aseptically.

Multi-compartment containers are known, allowing separate storage of diluents and drugs. These containers are disclosed, for example, in the number of the U.S. Patent. 4,608,043 to Larkin, U.S. Patent No. 5,176,634 for Smith et al., And Patent No. E.U.A. 5,462,526 to Barney et al. Patent Numbers of E.U.A. 4,608,043, 5,176,634 and 5,462,526 are expressly incorporated herein in their entirety for reference. The compartments of the containers disclosed in the above patents are separated from one another by brittle or vellable seals. The seals are broken by manipulation of the container so that the contents of the compartments can be mixed so that they form a solution that is delivered to the patient through a conventional IV configuration.

The containers in the market of current solutions are usually made of materials that include PVC plastic. The PVC material is usually somewhat gloomy in its appearance, making it difficult to inspect the contents of a container that is made of this material. As a consequence, inspecting such containers for leaks and moisture contamination is difficult. Inspection is further complicated when multiple compartment containers are used, where there is a need to verify whether a complete mixture of the drug and the diluent has been given prior to administration to a patient. In addition, various hazardous chemicals are used in the manufacture of PVC material that must be disposed of in an environmentally safe manner. PVC containers should be disposed of carefully after use, because PVC emits a toxic gas when it is incinerated and includes a toxic plasticizer that can exude in the surrounding environment if the container is buried in a dump this toxic plasticizer is also able to exude towards IV solutions, making PVC containers unsuitable for use with various types of medicinal fluids, and in particular with drugs in liquid form.

Typically, these flexible containers are manufactured from a pair of opposed planar sheets that are coupled together to form a body or shell. The formation of a body of particular size results from a fixed capacity of volume. Typically, containers are manufactured to maintain uniform volumes. This works well until a non-uniform volume is needed. In this situation, one option is to use only a portion of the solution stored in a large container. However, this option is expensive, uneconomic and dangerous. The user must also be very careful and only use the desired quantity or pre-written content of the fluid contained. In addition, any remaining solution may require specialized disposal.

The containers are also typically manufactured to a predetermined general overall size a few common general sizes. Generally this is because the overall size of the container determines its volume capacity, therefore relatively few predetermined volumes are provided in the containers. In addition, the manufacture, handling and sterilization of these containers requires expensive and highly complex machinery. This machinery is designed, in part, to handle the overall dimensions of the container. Therefore, it is desirable to provide a medical container which has a conventional general external size and which has a pleasing volume capacity relative to the conventional size. It is also desirable that the medicinal container be manufactured using the same machinery and handling equipment as that for containers of conventional size.

As with single-compartment containers, multi-compartment containers are typically constructed at predetermined compartment sizes. The diluent compartment is typically sized to maintain a sufficient amount of diluent to mix with the stored medicament and form a suitable solution. The size of the diluent compartment is also based on a particular dosage or stored amount of the medicinal solution. The volume of the diluent compartment can also be limited by the general external size of the container that must be constructed to fit into the container and handling equipment. However, in some applications it may be desired to increase the amount of diluent. At present this is not possible or requires a second container of diluent. Alternately, some applications may require an additional medication. It is therefore desired to provide a multi-compartment medical container having a conventional general external size with uniform compartment volume capabilities that can be permanently enlarged to increase the volume capacity of at least one of the compartments. It is also desirable that the container be manufactured to a predetermined size and general configuration to facilitate manufacture, sterilization and handling by the same machinery and processes.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides a flexible medicinal container for storing medicinal solutions which is capable of being permanently enlarged to increase its storage capacity. The present invention also provides a flexible medicinal container for storing medicinal solutions and powders which is manufactured to a uniform overall size and optionally enlarged to increase its storage capacity. By providing a flexible container having a front sheet and a back sheet that can be permanently stretched, the volume capacity of the container can be increased to a variety of sizes and shapes. By adding a simple and optional enlarged step to the manufacturing process of the container, the confinement of the volume of some containers can be enlarged while others can be maintained at a generally uniform or non-enlarged capacity. This advantageously allows the present containers to be manufactured, manage, manage substantially using current methods and equipment. In one aspect of the present invention, a flexible container for the storage and combined administration of a medicinal fluid is provided. The flexible container includes a substantially transparent front sheet having a first surface area. The front sheet is constructed from a flexible flat layer of a polymer film. A backsheet having a second surface area that is constructed from a flexible flat layer of a rolled product is disposed opposite to the front sheet. The front sheet and the back sheet are hermetically joined along a common peripheral rim to form a volumetric enclosure. A port is supported along the common peripheral flange and fluidly connected with the volumetric enclosure. At least one front sheet and one back sheet is permanently stretched to increase the storage capacity of the volumetric closure and therefore, of the container.

In another aspect of the present invention, the flexible container includes a substantially transparent front sheet having a first surface area. The front sheet is constructed from a flexible flat layer of a polypropylene-polyethylene copolymer combined with a styrene ethylene-butylene styrene thermoplastic elastomer. A back sheet of similar size having a second surface area is disposed opposite the front sheet. The backsheet is constructed from a flexible flat layer of a laminated product that includes an inner layer of a polypropylene-polyethylene copolymer combined with a styrene-ethylene-butylene thermoplastic styrene elastomer. This inner layer is disposed facing the opposite front sheet. The backsheet also includes an intermediate layer of aluminum foil and an outer thermoplastic layer having a higher melting point of the inner layer. The front layer and the back layer are hermetically joined along a portion of the common portion of the peripheral rim to form a volumetric closure.

A first peelable seal extends between a first side of the common peripheral rim and a second opposite side of the common peripheral rim. This first removable seal joins the front sheet and the back sheet to form a first compartment within the volumetric closure to contain a diluent. A second releasable seal extends between the first and second opposite sides of the common peripheral flange. This second peelable seal joins the front sheet and the back sheet to form a second compartment for containing a medicament and a third outlet compartment. The second compartment is located between the first compartment and the exit compartment.

The outlet connection port is supported along the common peripheral flange. The outlet connection port is fluidly connected to the outlet compartment. A diluent port is also supported along the common peripheral flange. The diluent port is fluidly connected over the first compartment through a break in the seal along the common peripheral flange. A drug port is also supported along the common peripheral rim. A drug port is fluidly connected to the second compartment through a second break in the seal along the common peripheral rim.

In still another aspect of the present invention, a method for forming a flexible container for the storage and combined administration of medicaments and diluents for IV solutions is disclosed. The method includes the steps of providing a substantially transparent front sheet and a flexible and vapor resistant back sheet. The provided face sheet is constructed from a flexible flat layer of a polymer film The backsheet is constructed from flat laminated product and multiple layers.The front sheet and the back sheet are sealed along the length of the sheet. its common peripheral flange to define a volumetric enclosure.

The method also includes the steps of providing first and second sacrificial ports that are supported along a first side of the common peripheral flange and fluidly connected to the volumetric enclosure. The first sacrificial port is separated apart from the second sacrificial port along this first side. The outlet connection port is supported along a second side of the common peripheral flange and is also fluidly connected to the volumetric enclosure.

The volumetric closure is expanded by inflation with a pressurized gas to permanently stretch at least the front sheet thereby increasing the volume capacity of the container. The pressurized gas is then released from the expanded container. The volumetric closure permanently stretched is then filled with a second gas. The sacrificial ports and the outbound connection port are then encapsulated to keep the container in an expanded configuration.

After the container has been permanently expanded, each of the sacrificial ports can be removed. This step includes removing a portion of the first side along the common peripheral flange. The front sheet is hermetically joined to the backsheet along the first side inward of the sacrificial ports to form a continuous permanent seal on the common peripheral rim.

Even in another aspect of the present invention, a method for increasing the capacity of a flexible container for the storage and administration of medicinal fluids is disclosed. The method includes providing a flexible container, such as the container of the present invention. The container provided includes a flexible flat front sheet opposite a flexible flat back sheet along a common plane. The front sheet is hermetically joined to the flexible backsheet along a common peripheral rim to form a volumetric closure. A port is connected to the container and is connected fluidly with the volumetric closure. The method includes the step of expanding the volumetric enclosure to permanently stretch at least the front sheet and therefore increase the volume capacity of the container.

The step of expanding the volumetric enclosure includes providing a multi-piece instrument that is configured to receive the volumetric closure. The instrument includes a lower instrument portion of an opposite upper portion of the instrument. The lower portion of the instrument has a flat lower flange that surrounds a concave lower region. In a similar configuration, the upper portion of the instrument has a concave rear region with a surrounding upper plane flange. The lower and upper planar flanges are generally opposed and configured to capture the common peripheral flange. The container is sandwiched between such portions of the instrument with the backsheet facing the lower concave region and the front sheet facing the upper concave region. The volumetric enclosure is then inflated with pressurized gas to permanently stretch the front and back blades outward and against the respective concave regions of the instrument. The volumetric closure is kept inflated for a sufficient time to overcome a substantial elastic rebound.

In yet another aspect of the present invention, a second method for forming a flexible container for the combined storage and administration of drugs and diluents for IV solutions is disclosed. The method includes providing a flexible and substantially transparent front sheet and constructed from a flat layer of a polymer. A vapor resistant flexible backsheet constructed from a multi-layer flat laminate is also provided. The front sheet and the back sheet are sealed along a portion of a common peripheral rim to define a volumetric closure. The front sheet and the backsheets are heated in a first localized area to fuse them along the first heated localized area and thus form a first peelable seal. The first seal extends between a first side of the common peripheral rim and a second opposite side of the peripheral rim. The first seal removably attaches the front sheet to the back sheet and therefore forms a first compartment within the volumetric closure to contain a. diluent. The front and back sheets are also heated along a second localized area to form a second peelable seal. The second peelable seal extends between the first side and the second opposite side of the common peripheral rim and separably seals the rear face sheets thereby to form a second compartment for containing a medicament. The second compartment is arranged between the first compartment and the exit compartment.

The method also includes providing a first sacrificial port interposed between the front and rear sheets and in communication with the first compartment. A second sacrificial port is also interposed between the front and back blades. However, a second sacrificial port is placed separately from the first sacrificial port and is fluidly connected to the second compartment. An outlet connection port is also interposed between the front and back blades. The outlet connection port is fluidly connected to the outlet compartment. The portion of the volumetric closure that forms the first compartment and then expands to permanently stretch the front sheet and the backsheet thereby increasing the volume capacity of the first compartment.

BRIEF DESCRIPTION OF THE DRAWINGS These and other features, aspects and advantages of the present invention will be more fully understood when considered with respect to the following detailed description, appended claims, and accompanying drawings wherein: Figure 1 is a semi-schematic front view of an exemplary embodiment of a container provided in accordance with the principles of the present invention; Figure 2 is a semi-schematic side cross-sectional view taken along the line 2-2 of Figure 1, showing the flexible flat sheets are formed in the container, with the thickness of the layers in the sheets exaggerated for its clarity; Figure 3 is a fragmentary semi-schematic cross-sectional view taken along line 3-3 of Figure 2 showing the configuration of the flexible sheets of a first embodiment of the container of the present invention; Figure 4 is a semi-schematic fragmentary cross-sectional view of the configuration of the flexible sheets of a first embodiment of the invention which represents an optional, transparent, high-barrier intermediate film; Figure 5 is a semi-schematic side cross-sectional view taken along line 2-2 of Figure 1, showing a first permanently enlarged compartment relative to Figure 2; Figure 6 is a semi-schematic front view of an exemplary embodiment of the container shown during manufacture in accordance with the principles of the present invention; Figure 7 is a schematic plan view of an embodiment of a modular apparatus for manufacturing the container in accordance with the principles of the present invention; Figure 8 is an alternative embodiment of a flexible container in accordance with the principles of the present invention; Figure 9 is a side elevational view of the flexible container of Figure 8; Figure 10 is a side elevational view of the flexible container of Figure 8 shown with the rear end plates permanently enlarged; Figure 11 is a perspective view of one embodiment of an instrument for permanently stretching front and back sheets of the flexible container in accordance with the principles of the present invention; Figure 12 is a perspective view of an upper portion of the instrument of Figure 11, showing the upper cavity; Figure 13 is a perspective view of one embodiment of an actuator housing for use with the instrument of Figure 11; Figure 14 is a semi-schematic perspective view of a handling container provided in accordance with the principles of the present invention, including a rail cartridge and a sealable film cover; Figure 15 is a semi-schematic planar view of the rail cartridge of Figure 14, showing a variety of flexible containers loaded on the rails; Figure 16 is a semi-schematic side elevational view of the loaded rail cartridge of the Figure showing how the flexible containers are held within the rails by the sacrificial ports; Y Figure 17 is a side elevational view of a flexible container of Figure 8 shown with the sacrificial ports removed and the permanent seal completed along the entire common peripheral rim.

DETAILED DESCRIPTION OF THE INVENTION Referring to Figures 1 and 2, schematic front and side cross-sectional views, respectively, of a preferred embodiment of a sterile, flexible container 10 provided in accordance with the practice of the principles of the present invention are shown. Although the container 10 can be seen in any orientation, for the purposes of the explanation, the position of the compartments of the container relative to one another are described with reference to the orientation of Figures 1 and 2. The container 10 is formed from of a generally flat front sheet 12 and a generally flat back or back sheet 14 (shown only in Figure 2). The back and front sheets 12 and 14 can be constructed from a flexible or single layer material or laminated products from multiple layers of flexible material which are described in greater detail below.

The sheets 12 and 14 forming the container 10 can be provided separately and arranged opposite one another along a common plane 15 (Figure 2). The sheets 12 and 14 are then sealed along a common peripheral flange 16 with a permanent seal. Preferably, the sealed peripheral peripheral rim 16 extends around the entire periphery of the container 10 to form a volumetric closure 17. Such peripheral seals may vary in configuration and width. A design seal, such as that depicted on the upper or upper side 18, the lower or lower side 20 of Figure 1, can be used to define grip areas that allow chemical personnel to handle container 10 and allow the container to hold onto, for example, a support platform IV. Alternatively, the back and front sheets 12 and 14 can be formed from a single sheet of film which is subsequently folded over and sealed together by means of a thermal seal extending around the periphery of the folded portions together the sheet of the film. However it is formed, the jointly sealed sheets are referred to herein as the "shell" or "body" of the container.

In the exemplary embodiment, the container 10 is divided into three separate compartments; a first or upper compartment 22, a secondary or intermediate compartment 23 and a lower or outlet compartment 24, each of which is sterile. The upper and intermediate compartments 22 and 23 are separated from each other by a first peelable seal 25, while the intermediate and lower compartments 23 and 24 are separated from one another by a second peelable seal 26. The peelable seals 25 and 26 extend between the first side 27 of the container 10 and a second opposite side 28. The removable seals 25 and 26 extend from the sealed peripheral peripheral bead 16 on the first side 27 to the sealed common peripheral flange 16 on the second side 28. The removable seals 25 and 26 join the lower faces of the front and back sheets 12 and 14 of the localized area or region of the seals.

A 'removable' seal as the term is used here, is a seal which is durable enough to allow normal handling of the container nevertheless peels openly, allowing separation of the front sheet from the back sheet, in the seal region , under hydraulic pressure that is applied when handling the container, therefore allows the mixing and distribution of the contents of the container A removable seal is formed by mixing together partially the polymeric material present in the adjacent lower faces of the front sheets The seal is obtained through a thermal sealing process and to which heat and pressure are applied to a localized area with time, temperatures and pressures that are described in more detail below. Conversely, the seal along the common peripheral flange 16 is significantly stronger than the "peelable" seals 25 and 26 and is not broken by the hydraulic pressures generated to separate the peelable seals.Each of the peelable seals, 25 and 26 , are individually configured to openly detach in a manner that preferentially allows the liquid medicament and liquid diluent to mix first, then allow the mixed components to be distributed.

In a typical use for the container 10 of the present invention, the upper compartment 22 is filled with a liquid diluent in the intermediate compartment 23 is filled with a medicament, typically provided in liquid form. The lower compartment 24 functions as a safety interconnection for an outlet connection port 30 and remains empty until the container is used. The outlet connection port 30 extends downward and comprises a body portion 38 and a nozzle 40 which is configured for attachment to a conventional IV delivery device. A stopper (not shown) is provided to cover the nozzle and maintain its sterility. The plug is removed just prior to the attachment of an IV arrangement to the outlet connection port 30. A variety of ribs 39 can be provided in a separate relationship on the body portion 38 of the outlet connection port 30 to provide a surface easily Attachable and to facilitate the union with an IV arrangement.

The materials used to construct the front and back sheets of the container 10 are selected based on the material to be stored there. Preferably, at least one of the sheets is transparent to allow the contents of the container to be visually inspected and to allow the level of the container solution to be visually verified during administration. The materials suitable for the manufacture of the transparent sheet are polymers and films of multilayer and single layer laminated polymers.

In particular, whether they are constructed of a polymer film of a multilayer or a single layer laminate, the materials comprising the front and back sheets 14 of the container 10 are chosen for their clarity and transparency. Conventional polyvinyl chloride (PVC) container materials are generally somewhat gloomy in appearance, making it difficult to properly observe the interior of the container and determine the levels of any fluid that is contained there or the presence of particulate matter. This is a particularly dangerous situation when medications are administered intravenously. It is imperative that a nurse or clinician be able to say, at a glance, that any similar medication being administered is from a medical container that is free of particulate matter.

Referring now to Figure 3, a fragmentary schematic cross section of a mode of the container 10 is shown. As shown, the front sheet 12 is constructed of a single layer, transparent thermoplastic polymer film 44. The transparent film 44 can be manufactured from a flat layer or sheet comprising a mixture of about 80 percent by weight polypropylene-polyethylene copolymer available from Fina Oil and Chemical Company of Deerpark, Texas, which has a commercial designation of Z9450, and about 20% by weight of a styrene ethylene-butylene styrene thermoplastic elastomer, available from Shell Chemical Corporation under the brand name KRATON having a trade designation of G1652. The thermoplastic elastomer G1652 is a two-phase polymer with polystyrene domains (terminal blocks) in a poly (ethylene-butylene) rubber matrix and is typically provided in the form of a migajon. In practice, the film is made by mixing the granules of the Z9450 co-polymer resin and the G1652 thermoplastic elastomer, in the form of a crumb, in a weight ratio of 80 percent / 20 percent, in a high shear mixer and melting and regranulating the mixture. Combining G1652 granular material in high shear equipment can cause the temperature to rise, therefore care must be taken that the temperature is not allowed to exceed approximately 260 ° C. Subsequently, the transparent film 44 is formed from blended granules in a commercial extrusion apparatus.

The transparent polymer layer 44 comprising the front sheet 12 can be constructed with various thicknesses, depending on the use to which the container is put and the durability that is required for that particular use. Suitable thicknesses for the material comprising the front sheet 12 can range from about 3 to about 15 millimeters, but in the embodiment of the illustrated container, the transparent polymer film 44 comprising the front sheet 12 is preferably approximately 12 millimeters thickness. Although the composite material that is chosen to form transparent polymer film 44 (alternatively may be referred to as the "80:20 film") was chosen based on its clarity and transparency, the film 44 is also particularly suitable for forming both the seals "removable" as the permanent seals, such that the permanent seal along the common peripheral rim 16 of the container 10. As described in greater detail below, the 80:20 film, in accordance with the invention, is capable of accommodating both the low temperature, detachable seal formation processes and the high temperature permanent seal without affecting the integrity of the material or its ability to provide an effective removable or permanent seal.

For certain medical solutions, including certain combinations of diluents and medicaments, the backsheet 14 can be formed with the same single-layer configuration composition as the front sheet 12. Alternatively, the multilayer films, which include layers that are impermeable to humidity and light are therefore able to extend the shelf life of a full container, they are the preferred films for the construction of the backsheet. As illustrated, a laminated back sheet 3 of 3 layers can be employed. Preferably, the back laminate sheet 14 is a flexible planar sheet that is impervious to water vapor and light. This configuration preserves the effectiveness and activity of the solution e.n a single compartment container 10 and the binary components (in unmixed medicament and diluting liquids) with multi-compartment containers and therefore, increase shelf life of the filled container.

In the exemplary embodiment illustrated, the backsheet 14 includes an internal seal or a seal layer A 6 on its inward facing surface. This inner seal layer 46 can be constructed from a blend of 80 percent / 20 weight / weight percent of a polypropylene-polyethylene copolymer and a styrene-ethylene-butylene styrene thermoplastic elastomer having the mixture a thickness of about 3 to 6 mm (the film 80:20). Preferably, the inner seal layer 46 (the film layer 80:20) can be about 6 millimeters thick, which is attached by means of a transparent internal adhesive 48 to an intermediate layer 50. Preferably, this intermediate layer 50 it can be from about 0.7 millimeters to 1.3 millimeters, and more preferably about 1.0 millimeters, of aluminum foil layer with a high barrier. An outer layer 54 is provided on the surface facing away from the backsheet 14 and is bonded to the layer of high-foil aluminum foil 50 by means of a suitable transparent adhesive 52.

The inner layer of adhesive 48 may comprise a modified aliphatic polyurethane polyester adhesive, available from Liofol Company of Cary, North Carolina, under the trade name of TYCEL 7909. The outer layer of adhesive 52 may comprise a modified aromatic polyurethane polyester adhesive , also available from Liofol Company of Cary, North Carolina, under the trade name of TYCEL 7900. The aliphatic adhesive comprising the inner layer of adhesive 48 can also be used for the outer layer of adhesive 52, although in reverse is not the case. The aromatic adhesive, while providing a stronger bond than the aliphatic version, potential to introduce extremely undesirable aromatic compounds in either the liquid diluent or the liquid medicament, through the 80:20 film layer. Accordingly, the aromatic adhesive, when used, is only used when the aluminum foil layer 50 is interposed as a barrier between it and the volume of the container 17 within the container 10.

The aluminum foil layer 50 is suitably constructed from commercially available 1.0 mm aluminum foil, such as ALCAN 1145, available from Alean Rolled Products Company, of Louisville, Kentucky. When the aluminum foil layer 50 remains exposed as the outer layer of the backsheet 14, the heat sealing process, used to form both the seal along the common peripheral flange 16 and the removable transverse seals 25 and 26 may damage the seal. sheet of 50 aluminum foil and degrade its integrity and ability to provide a barrier. The high temperature outer layer 54 is provided to prevent this damage. Preferably, the outer layer 54 is constructed of a relatively high melt polymer that functions as a protective layer of the aluminum film and prevents contact in the intermediate aluminum foil layer 50 and the hot plates of a heat sealing apparatus. In addition, the high temperature layer 54 functions as a thermal seal release layer (also called mold deliberation) because the material does not melt or stick to the heat seal plates at the temperatures used during the process of forming the heat seal. seal. Therefore the pressure and temperature can be applied to the outside of the container without the need for special coatings on the plates. Preferably, the outer layer 54 can have a higher melting temperature than the inner sealing layer 46.

The high temperature outer layer 54 is preferably a polyethylene terephthalate (hereinafter referred to as PET) available from Rhone-Poulanc under the tradename TERPHANE 10.21, having a thickness in the range of about 0.4 to about 0.06 millimeters. In the illustrated embodiment, the thickness dimensions of the components of the multilayer laminated film 14 are preferably approximately 0.48 millimeters for the outer layer of high temperature polyester 54, and approximately 1.0 millimeters for the high aluminum foil layer. impediment 50, and approximately 6.0 millimeters for the film 46 of internal sealing layer 80:20.

It is discovered that preferable material options for the front and back sheets 12 and 14, which result in optimum performance of the peel-off seals 25 and 26, incorporate an interconnect seal layer in each sheet comprising the 80:20 film. Alternatively, the sealing layers of the inner face of the front and back sheets may comprise thermoplastic styrene ethylene-butylene styrene and polypropylene-polyethylene copolymer elastomer mixtures having different relative percentages. The relative percentages that are used depend on the characteristics of the various seals that are contemplated for their use and connection with a particular medical container and the temperature and pressure parameters of the seal formation process. Other types of flexible films may be useful in the construction of the front and back sheets in the shell of the container 10 of the present invention, as well as the sealing layers of the inner face in both sheets, are described in the Patent Numbers of USA 4,803,102, 4,910,085, 5,176,634 and 5,462,526, the complete descriptions which are expressly incorporated herein for reference. In certain uses, particularly with multi-compartment containers, such as the container illustrated in Figures 1-2, additional protection may be desirable. This may especially true when the medicament is susceptible to water vapor contamination or degradation caused by radiation of the visible or UV portion of the spectrum and therefore, requires additional protection over the portion of the front sheet 12 that covers the compartment. intermediate (of the medicament) 23. However, this additional protection can be provided over any number of compartments or even over the entire front sheet 12. Additional protection can be provided to exclude moisture, oxygen, and / or light transmission through the portion of the front sheet 12 comprising the secondary or intermediate compartment 23 and to protect the medicament from degradation.

Such additional protection comprises that the container 10 is stored for substantial periods of time without losing medicinal efficacy.

Referring particularly to Figures 2 and 3, an opaque film 55 having high hindrance properties is used to cover the intermediate compartment 23. The opaque film 55 interposes a barrier to moist vapor and oxygen-free permeability of the medicament compartment. and, in the exemplary embodiment, comprises a multi-layered laminated structure including a high-barrier aluminum foil layer. The use of an opaque foil laminate product helps prevent the medicament contained in the intermediate compartment 23 from degrading due to exposure to invisible light and UV radiation. Therefore, in the illustrated embodiment, the opaque aluminum foil comprising both the protective film 55 and the backsheet 14 includes the intermediate compartment 23 and prevents the penetration of invisible light from the UV spectrum into the intermediate compartment 23 from either direction. The high barrier protective film 55 may be a multi-layer laminate, it is constructed from an inner seal layer 56 on its inward facing surface. In the exemplary embodiment, the sealing layer 56 is a coextrusion-coated soft resin comprising a modified ethylene vinyl acetate polymer available from Dupont Chemical Company under the tradename APPEEL 1181, provided in a thickness of from about 0.2 to about 0.4 millimeters. A layer of aluminum foil, such as ALCAN 1145, from about 0.7 to about 1.3, and preferably from about 1.0 millimeter in thickness attaching to the inner seal layer 56 by means of a suitable transparent adhesive 57. A releasing outer layer of the thermal seal 60 comprising a polyethylene terephthalate (PET) film, such as TERPHAJSTE 10.2, of about 0.48 millimeters in thickness, forms the face-out surface of the high-barrier protective film 55. The term 60 release seal layer is it joins the aluminum foil layer 58 by means of a suitable transparent adhesive 59. The adhesive layers 57 and 59, of the present embodiment, suitably comprise an aliphatic polyester polyurethane adhesive available from Liofol Company under the tradename of TYCEL 7909. Alternatively , the transparent outer adhesive 59 may comprise a modified polyurethane polyester aromatic adhesive, also Also available from the Liofol Company, under the trade name of TYCEL 7900. Due to the dangerous companions that the aromatic compounds drain into either the liquid diluent or the liquid medication, the aromatic adhesive is used only on the outside of the aluminum foil layer 58. The inner layer of adhesive 57 preferably comprises an aliphatic adhesive. Because the inner sealing layer 56 of the high barrier protective film 55 can be a co-extrusion coated resin, it is capable of forming a peelable seal, over a wide temperature range when applied to several different materials. Materials to which a coextrusion coated resin can be formed into a releasable seal include acrylonitrile-butadiene-styrene (ABS), high density polyethylene (HDPE), high impact polystyrene (HIPS), polypropylene (PP), polystyrene (PS), polyvinylchloride (PVC), and the 80:20 film comprising the front sheet 12 of the container. The high barrier protective film 55 can therefore be removably (detachably or detachably) attached to the outer surface of the front sheet 12 covering the intermediate or medicament compartment 23.

Preferably, the high barrier protective film 55 is removable (removable or detachable) from the container 10 before use, to allow a visual examination of the condition of the medicament in the medication compartment 23. In the exemplary embodiment, it is best seen in connection with Figure 1, a protective film 55 includes an extendable tab 62 that can be gripped in order to detach the protective film 55 from the transparent front film 12. The contents of the drug compartment 23 are therefore arranged for easy inspection visual.

The high barrier protective film 55 can be sealed and adhered to only a portion of the front sheet 12. Preferably, those portions of the high barrier protective film 55 if not sealed to the adjacent material of the front sheet 12 define an arrangement or regular pattern of generally circular raised dimples 51 that are the tactile residue of a thermal seal bar in which a rectangular array of pits has been cut. When the heat seal bar is pressed onto the surface of the high barrier protective film 55, a heat seal is provided only on the surface of contact regions of the heat seal bar and not in the regions where the material of the bar It has been removed (the holes). Since pressure is also applied during the process along with heat, the high barrier protective film 55 takes a reverse print of the thermal sealing head, thereby giving rise to the textured surface with high dimples. The dimples 51 allow the high barrier protective film 55 to be suitably sealed to the underlying material (the front sheet) of the medical container but, at the same time, provides for easy removal of the film 55 without application of undue force. If the protective layer 55 as a whole is thermally sealed in the front sheet 12, a relatively strong bond is created in an amount of force greater than the desired one required to completely detach it. By reducing the adhered surface area of the seal, a smaller force (proportional to the sealing area) is required to remove the opaque opaque barrier. It is apparent from the foregoing description that the amount of force required to remove the aluminum release strip is inversely proportional to the number of dimples (51 of Figure 1) that are formed in the film 55. Depending on the use that is put on In the medical container, a high-barrier protective layer more or less easily removable can be easily constructed only by increasing or decreasing the number of dimples that form in the layer during the thermal sealing process. It should be noted, however, that the high impediment film 55 has its total periphery, with the exception of the tongue 62, thermally sealed to the underlying material of the container. Thus forming a total peripheral seal around the high impediment film 55 ensures that the impeding properties of the film extend completely throughout the drug compartment 23.

In practical use, the filled container 10 can be stored for a period of time in view of an eventual need. Typically, before dispensing, a pharmacist or other user removes the high impediment aluminum foil layer 55 from the front sheet 12 of the container 10 in order to visually verify the integrity of the contents. If the container 10 is not put into use at the moment, it is returned to storage and dispensed again to the next demand. Removal of the high barrier release film 55 leaves the contents of the container, or particularly, of the drugs in the intermediate compartment 23 susceptible to degradation by moisture, light and permeable oxygen. It is desirable that filled containers 10 in accordance with the present invention be capable of being stored for periods of up to 30 days before use without the medical solution or medicament being severely degraded by exposure to moisture and free oxygen after which The high barrier protective film has been removed from the medication compartment. Accordingly, and as illustrated in Figure 4, an intermediate high-barrier laminated transparent film 64 is optionally interposed between the protective film containing the high-barrier aluminum paper 55 and the 80:20 material of the front sheet 12 of the container . Preferably, this intermediate laminated film 64 is disposed on the portion of the front sheet 12 covering the intermediate compartment 23. In this configuration, the high barrier transparent intermediate film 64 covers and protects the contents of the intermediate compartment 23 after which the protective film is peelable High impediment 55 is removed from container 10. Intermediate high barrier 64 transparent film exhibits barrier properties that protect medical solutions and medications from at least steam moisture and oxygen permeation for a substantial period which, depending on the The specific activity of the medication, can be as long as 30 days. In other words, the high barrier opaque protective film 55 in combination with the high hindrance transparent intermediate film 64 can be used to form a high barrier protective coating on the intermediate compartment 23. With regard to the characterization of the protective coating as a coating of 'high' impediment, there is the degree to which the protective coating is impervious to various penetrating gases Polymers are categorized by the degree to which they restrict the passage of penetrating gases, for example, oxygen or vapor moisture.

The categories range from 'high' impairment (low permeability) to 'low' impairment (high permeability).

The category in which the polymer is classified may vary according to the penetrating gas. As used herein, the term "high" -imperiment, when referring to vapor permeability, means a film with a permeability of less than about 1.5 g / mm / m2 / 24 hr / atm, at 30 ° C, 100 RH percent As used herein, the term "high" -impediment when referring to oxygen permeability, means a film with a permeability less than about 50 cc / mm / m2 / 24 hr / atm, at 25 ° C, 100 percent RH The high barrier interim transparent film 64 may include a high barrier three layer laminate structure which is significantly resistant to the permeability of free oxygen and water vapor to thereby protect the contents of the medicament compartment and increase the shelf life of a binary container. In an illustrated embodiment, the intermediate film layer of the laminate 64 includes an outer layer 66 of silica deposited polyethylene terephthalate (also called SiOx or PET coated polyester, coated by SiOx) available from Mitsubishi Kasei under the tradename TECH BARRIER H. The sealant layer 56 of the high hindrance protective film 55 is contacted with the outer layer 66 of the intermediate laminated film 64. An intermediate layer 68 comprising a polyvinylalcohol (PVA) film (coated with SiOx) deposited with silica available of Mitsubishi Kasei under the trade name of TECH BARRIER S joins the outer layer 66. On its inwardly facing surface, the high-barrier transparent intermediate film 64 suitably comprises an inner sealing layer 69 which is formed of a polypropylene-polyethylene copolymer. The copolymer can be blended with a styrene ethylene-butylene styrene thermoplastic elastomer in various proportions, but a 100 percent polyethylene-polyethylene copolymer layer is preferred. The individual layers of laminated intermediate film 64 are adhesively bonded to one another. For clarity, these adhesive layers are not shown here, but comprise a modified aliphatic polyester polyurethane laminate available from the Liofol Company under the tradename of TYCEL 7909. The inner seal layer 69 is securely fixed to the outer surface of the front sheet 12 by a permanent and appropriate ultrasonic or thermal seal, a pressure adhesive seal, or the like. The high barrier interim transparent laminated film 64 is dimensioned, horizontally and vertically, to cover the entire surface area of the medicament compartment also extends to cover the detachable and permanent seals that form adjacent to the medication compartment.

Similar to the flexible and thermoplastic materials comprising the front sheet 12, the three layer laminate structure of the intermediate layer 64 is substantially optically clear and transparent to allow inspection of the contents of the drug compartment 23. Therefore, unlike the Polyvinyl chloride (PVC), and other similar materials, are quite hazy (translucent), the intermediate layer 64 of the present invention is visually transparent while conferring considerable protection against moisture and degradation of free oxygen. In particular, the impeding properties of the clear laminal intermediate film of high hindrance 64 are substantially greater than those of conventional films, such as low density polyethylene (LDPE), medium density polyethylene (MDPE), linear polyethylene of low density (LLDPE), ethylene-vinylacetate (EVA) copolymers, or mixtures of these polymers, in areas important for container operation, for example permeability to moisture and oxygen. The permeability and oxygen of the intermediate layer 64 is approximately 10 cc / mm / m2 / 24 hr / atm. Conversely, the oxygen permeability of the EVA, LDPE and MDPE copolymers, respectively, are approximately 2500 (EVA 5 percent), 8300 (LDPE), and 8500 (MDPE) cc / mm / m2 / 24 hr / atm. The oxygen permeability of LLDPE is approximately the same or slightly higher than for LDPE. Therefore, the oxygen permeability of the high barrier interim transparent layer 64 is orders of magnitude less than the oxygen permeability of the polymers typically used to build binary medicinal containers. In other words, the impeding properties of the high hindrance intermediate layer 64 are improved by several orders of magnitude over the impeding properties of the polymers typically used to build these containers.

Due to the impeding properties of the intermediate laminated film, the protective film 55 containing the peelable aluminum foil can be removed by a pharmacist in order to carry out a visual inspection of the contents of the container before administration, and the container it can be stored for a reasonable additional period of time without the danger of drug degradation induced by oxygen or moisture. Once the aluminum foil protective layer is removed, it is desirable that the container have a shelf life of about 30 days. After the removal of the aluminum foil layer, the precise shelf life of the container that includes the clear film of high impediment laminate 64 necessarily depends on the sensitivity to moisture or oxygen of the drug that is contained in the intermediate compartment 23. Drugs with a relatively low sensitivity to moisture are able to retain their effectiveness for periods substantially greater than 30 days by virtue of being protected by the laminated clear film of high impediment 64. In addition, drugs with an extreme sensitivity to moisture, that is, those that normally begin to lose their effectiveness to exposure to water vapor by removing the aluminum foil layer, can be stored for periods of up to 2 weeks' without losing effectiveness because the properties of deterrent to the humidity of the clear high impediment film that lie on top of the intermediate compartment 23.

Although the intermediate film 64 has been described in the exemplary embodiment as being fixed to the outer surface of the medicament compartment, it is apparent to one skilled in the art that the intermediate layer can be sized to cover both the intermediate and primary compartments if desired . The intermediate film 64 can also be used to cover the entire front sheet 12. The manner of linking the intermediate layer 64 to the external surface of the container can also vary without deviating from the spirit of the scope of the invention. The intermediate layer 64 can permanently secure the outer surface of the container by a suitable adhesive, and as by a permanent ultrasonic or thermal seal. Alternatively, the intermediate film 64 can be provided removably on the surface of the container by adjusting the temperature and pressure characteristics of a thermal seal in order to make the seal detachable. In this case, the film 64 can detach the container 10 as is the case with the opaque laminate film of high hindrance 55.

It is mentioned that in the exemplary embodiment, the medicament is described as being in the form of a liquid. The medication can also be in the form of a colloid, crystalloid, liquid concentrate, emulsion, or whatever it looks like. In addition, the medicament can be provided as a dry powder such as antibiotic compounds or antiemetic compounds, with non-limiting examples of these being; cefizolin, cefuroxime, cefotaxime, cefoxitin, ampicillin, nafcillin, erythromycin, ceftriaxone, metoclopramide and ticar / clav. Intermediate compartment 23 does not need to be filled with a drug, per se. Other medical compounds such as freeze-dried fractions of blood, blood factor VIII, factor IX, prothrombin complex, and the like, are particularly suitable for dispensing from a container in accordance with the invention. While the container of the present invention has been described with multiple compartments and particularly with a single drug and diluent compartment, the single compartment containers can be provided in accordance with the present invention as described in greater detail below. In addition, containers that have multiple compartments filled with different diluents and / or different medicaments may also be provided in accordance with the present invention.

While the preferred materials for the high barrier intermediate clear film 64 may include both an oxygen barrier layer and a moisture barrier layer, alternative materials may be used to provide a cover for the drug compartment that is adaptable for various particular uses. For example, one of the high impediment layers can be omitted by giving an intermediate high impediment film that includes only one layer of moisture barrier or only one layer of oxygen barrier. Moreover, the high hindrance intermediate film 64 may include a moisture barrier layer, as described above, in combination with a thermal seal release layer that is constructed from a high melting temperature material that also exhibits some properties of impediment to oxygen.

Preferably, the flexible container 10 can be manufactured to a particular size in general or to a few sizes. This limits the need to duplicate machinery or alternatively multiple operations and mechanisms of machinery. As discussed previously, a general single size of the container, such as the rectangular dimensions on the common peripheral flange 16, facilitates the handling of the container as well as the administration of the medicinal solutions contained therein. In particular, this allows the manufacture, handling, sterilization and marking of the containers 10 so that it is carried out with similar or identical machineries and procedures and eliminates the need for multiple operations and machining. However, restricting the overall size of container 10 limits the volume of medicinal solution that each compartment can hold.

In order to increase the capacity of the container 10, and in accordance with the principles of the present invention, at least one of the front sheets 12 and subsequent sheets 14 is stretched or otherwise stretched. The capacity of the volume of the container 10 is permanently enlarged, which allows the manufacture of a unique container design to store and administer a greater variety and combination of medical solutions and medicines. Since the enlarged containers remain unchanged from conventionally sized containers, there is no need to machine to manufacture these specially sized bags. This is especially advantageous where smaller quantities of containers may be needed otherwise they are not manufactured due to the costs.

Referring to Figure 5, a container of the conventional size 10 is shown with each of the front sheets 12 and back sheets 14 permanently stretched to increase the capacity of the first compartment 22. More particularly, the front sheet 12 and the back sheet 14 , each one includes a respective surface area 70. These respective surface areas 70 oppose one another along a common plane 71 which is generally defined along the common peripheral flange 16. The front sheet 12 and the sheet 14 have been enlarged by a permanent stretch in the respective surface areas 70.

In the embodiment illustrated, only the first compartment 22 has been enlarged. This configuration can be particularly useful when an amount greater than the conventional diluent is desired for use with a conventional amount of medicament. The front sheet 12 is further stretched or stretched further in relation to the back sheet 14. This is particularly true where the back sheet 14 includes an aluminum or otherwise less expandable layer.

MANUFACTURE AND ASSEMBLY OF THE CONTAINER Referring now to Figure 6, a method of manufacturing and assembling the flexible container 10 is described in accordance with the practice and principles of the invention. The front sheet 12 and the back sheet 14 are disposed opposite one another. The inward facing layer of the front sheet 12 comprises a film 80:20, which is brought into contact with the 80:20 film layer facing inwardly of the back sheet 14. Other interconnected films can be used and be inside. of the scope and contemplation of the present invention.

The composition of the front and back sheets 12 and 14 of the container 10, allow the creation of a seal along the common peripheral flange 16 and the removable seals 25 and 26 using thermal sealing techniques. Dies or hot rods are used at different temperatures, pressures and application times to bring the interconnected portions of the materials and laminates used at temperatures near or above their melting points to allow the migration of the material through interconnection to it 'to form a union of strength and desired characteristics.

Either for a single-layer film or multi-layer laminated film, comprising the front sheet 12 and the laminated aluminum foil product comprising the back sheet 14, a method for manufacturing the container 10 is described. The method comprises cutting the front and back sheets of the container to the desired vertical dimensions of the container, but enlarged in the horizontal dimension. If the container 10 is constructed with a single-layer front sheet 12, the protective layer 55 containing the high-barrier aluminum paper (of Figure 3) and the high-barrier transparent intermediate layer (64 of Figure 4), which they comprise the high impediment covers for the second compartment 23 are cut to size, placed on the area that will become the intermediate or medicament compartment, and which is sequentially attached to the front sheet 12 of the container. In accordance with the invention, the high barrier transparent intermediate layer 64 is first laminated on the surface of the front sheet 12 followed by the protective layer 55 containing the aluminum foil.

Specifically, the high-barrier transparent intermediate layer 64 placed over the second compartment 23 is held in place by a pair of rods or similar devices while being laminated on the surface of the front sheet 12. The portion of the layer 64 in contact with the rods is, therefore, not accessible for, for example, the thermal sealing head, resulting in a small portion of the film not sealing on the surface of the front sheet. The residue of the use of the rods to ensure the high barrier intermediate transparent layer in position to an unsealed area having a rod contact imprint. The contact surface of the rod is finally circular and results in two unsealed circulated regions 41 which remain visible due to the inverse imprint caused by the pressure applied during the sealing process. After lamination of the intermediate layer 64, the aluminum foil layer 55 is applied on the surface thereof, using a die with thermal seal design as described above.

After the fixing of the aluminum foil layer 55 and the high impediment transparent layer, the front and back sheets 12 and 14 can be coupled together and permanently sealed together along the common peripheral flange 16. The connection port outlet 30 may include a rim 34 that is inserted into its desired end position between the front and rear sheets 12 and 14 is fluidly connected to the outlet compartment 24. The outlet connection port 30 may be injection molded and may have a composition of 40 percent FINA Z9450 polyethylene-polypropylene copolymer and 60 percent shell Kraton G1652 styrene ethylene-butylene styrene thermoplastic delastomer. After the insertion of the outlet connection port 30 along the common peripheral flange 16, a hot die is used to create a permanent seal between the piping of the outlet connection port 34 and the underside 20 of the front sheets and rear 12 and 14 adjacent to trim 34.

Removable seals 25 and 26, and any additional removable seals, which divide the compartments and the container 10 are then made using, for example, double hot bars comprising a front bar in alignment with a rear bar forcing the front and rear sheets 12 and 14 between them to form the seals 25 and 26 For example, the front bar can be contacted with the previously combined high-barrier protective film 55, intermediate films 64, and front sheet 12. This front bar is maintained at a temperature (in the range of about 118 ° C to about 129.5 ° C) and may optionally include a thin rubber coating to ensure uniform application of pressure. The double bars are pressed into contact with the front and back sheets with a pressure in the range of about 230 psi to about 340 psi and are maintained at that temperature and pressure for a period of time from about 1.5 to about 2.5 seconds. The removable seals 25 and 26 can also be made individually with a single double-bar conformation, or simultaneously with a double-bar twin conformation. Any additional removable seal can be easily accommodated by a triple double bar conformation.

After the formation of the release seals 25 and 26, the front and back sheets 12 and 14 are coupled together and sealed by a permanent peripheral thermal seal extending along the common peripheral flange 16. This permanent seal is separated from the embossed rim of the first side 27 of the container and provides openings between the front and rear sheets 12 and 14. In other words, the permanent seal is continuous along the upper vertical side 18, the second side 28 and the lower vertical side 20 is breaks along the first side 27 to allow access of the first and second compartments 22 and 23. The permanent seal does not affect the fluid connection of outlet connection port 30 with the outlet compartment 24.

A first sacrificial port 72 can be inserted between the front and back sheets 12 and 14 and fluidly connected to the first compartment 22. A similar configuration, a second sacrificial port 74 can be inserted between the front and rear sheets 12 and 14 and connect fluidly with the second compartment 22. Preferably, each of the sacrificial ports 72 are placed and supported along the common peripheral flange 16 of the first side 27 within the openings in the permanent thermal seal. The sacrificial ports can be supported by the common peripheral flange 16 in a configuration similar to that of the outlet connection port 30. Therefore, each of the sacrificial ports 72 and 74 includes sharp rims of mount 76 that are interposed and sealed between the front and back sheets 12 and 14 along the common peripheral rim 16 of the first side 27. The sacrificial ports 72 and 74 can be injection molded. Preferably, the sacrificial ports 72 and 74 are constructed from a cheap thermoplastic material, since they will be removed and thrown at a later stage in the process. In a particularity, the sacrificial ports 72 and 74 can be constructed of a 're-grinding' material of 80:20 film, simple polypropylene or any other similar material.

The sacrificial ports 72 and 74 are an important feature of the present invention and provide a means to aseptically fill a single-compartment container with a medicinal solution or a multi-compartment container with liquid diluents in the first compartment 22 and a medicament. or something similar in the second compartment 23. In addition, the sacrificial ports 72 and 74 are provided with structure to allow the ports and, therefore, the flexible medical container 10 to be held and manipulated by automated robotic machinery.

As shown, each sacrificial port 72 and 74 includes a lower rim 78 and a separate upper rim 80. Each of the trims 78 and 80 may generally be rectangular or otherwise formed to facilitate handling. In particular, each of the trims 78 and 80 can be configured in a particular manner for operation with support and handling equipment. An internal bore through each of the sacrificial ports 72 and 74 provides communication with each of the respective compartments 22 and 23.

A cap or cap 82 generally cylindrical is provided for each of the sacrificial ports 72 and 74. The caps 82 can be constructed having an outer diameter that is slightly larger than the inner bore of each of the sacrificial ports 72 and 74, of Such that when the plug 82 is inserted, the interconnection between the external diameter of the lid and the internal diameter of the port provides a hermetic seal. This friction seal is required to prevent particles from entering the container 10 before filling and to prevent powdered medicaments or liquid diluents that leak out after the container has been aseptically filled. Preferably, each of the covers 82 may have a beveled bottom edge, such as to engage a similar bevel in each of the sacrificial ports 72 and 74 respectively.

In addition to the piping 78 and 80 in the ports, a pair of vertically spaced piping is also provided in the lid 82. An illustrated exemplary embodiment, a generally circumferential top piping 84 defines the top portion of the cover 82. The upper piping allows for an "removal" mechanism for crimping the lower portion of the upper edging 110 and providing a means of removing the layer vertically out of its respective port barrel 72 and 74. A lower edging 86 may also be provided on the cover 82. The lower edging 86 limits the depth of penetration of the lid 82 during insertion into the barrel of the port 72 and 74 when it is re-seated after a filling operation The lower border 86 may be fully circumferential or alternatively may be implemented as a partial edging which defines a simple lateral extension from the body of the lid 82. The upper and lower piping 84 and 86 are separated from one another , along the body of the lid 82. These manufacturing steps form the flexible container 10 described to have a conventional configuration with non-enlarged compartments 22 and 23. As discussed previously, the first compartment 22 can be enlarged to implement the volume of storage available for a diluent. In a similar manner, the second compartment and the outlet compartment 23 and 24 can also be enlarged. This may include permanently stretching at least one of the front sheets 12 or the back sheets 14 by inflating the respective compartment 22, 23 and 24 with a pressurized gas as described in greater detail below.

APPARATUS FOR MANUFACTURING THE CONTAINER In accordance with the practice of the principles of the present invention, a method and apparatus for manufacturing the container 10 of Figure 6, in connection with Figure 7 is now described. As is apparent from the following description of an apparatus for the manufacture of a container, both the apparatus and the procedure are adapted to suit the manufacture of medical containers with front and back sheets comprising either single-layer or multi-layer laminated peripherals. Furthermore, it is evident from the following description that the number, shape, configuration and location of the various seals of the container 10 of Figure 6 can easily be changed, or indeed even omitted, due to the modular configuration of the components of the container. apparatus.

Figure 7 is a semi-schematic plan view in an exemplary embodiment of a machinery for manufacturing a container 88 provided in accordance with the present invention, showing the arrangement and placement of various stamp-forming stations and the arrangement and configuration of the stamps. rolls containers of the primary supply of the film lattice.

The bulk material for the front and back sheets of the container (12 and 14 of Figure 2, for example) is fed to the container manufacturing machinery 88 in the form of respective rolls of bulk film framework 90 and 92. , which are assembled in the roll stations for supply of web material at the entrance end of the container's manufacturing machinery 88. The web material of, for example, front sheet supply roll 90 slides through a station jump 94 that works to keep the interlaced material at an adequate tension while the interlaced material is pulled through the remaining stations of the manufacturing machinery 88.

After jump station 94, the web material is transported in a vacuum by feed wheels after a first clearing station of the web material 96 then through a series of optional impediment film application stations 98 and 100, arranged in series along the course of the framework material. If the container 10 is being constructed in the manner briefly described, i.e., including a single layer front sheet 12, a high barrier interim transparent film (64 of Figure 4) a protective layer 55 containing high impediment aluminum paper, the high hindrance covers the second compartment 23 is cut first to the size, then it is placed on the portion of the surface area 70 which will be returned to the second compartment, then sequentially fixed to the front sheet 12 of the container 10 at the impeding peripheral application stations 98 and 100 respectively. In accordance with the invention, the high-barrier transparent intermediate layer is first laminated on the surface 70 of the front sheet 12 at the application station 98 and the protective layer 55 containing the aluminum foil is coated therein at the application station 100. .

Similarly, the lattice material forming the backsheet of the container slides from its bulk frame supply roll 92 through a corresponding hop station 102, which is conveyed by vacuum feeding wheels through a corresponding station. of clearance of the framework 104.

When the continuous peripheral edges of the lattice materials 90 of the front and rear sheets 90 and 92 leave their respective preparation stages, they are fed into register with each other so that the 80:20 surfaces of each continuous flat film measure towards the 80:20 flat surface of the other movie. Once both continuous film webs 90 and 92 are put in register, the web material is continuously indexed and moved longitudinally through the seal core 106 of the manufacturing apparatus 88. The first (diluent) and second (drug) Sacrificial ports 72 and 74 are located along the sandwich of the truss material and are placed between the film webs of the back and front sheet, various seals are formed sequentially in the sandwich material of the truss to thereby join the truss materials into jointly form and substantially manufacture the container 10 in a suitable intermediate stage to expand and fill aseptically, as best illustrated in Figure 6. In accordance with the practice of the principles of the present invention, the manufacturing core 106 of the seal machinery comprises a variety of sealing braids and port insertion stations, formed in series along the course of travel of the sandwich container of the material framing ^ of the film. The first of this station is a charging station for joint ports 108, wherein a particular port, or an outlet connecting port 30 is inserted in its proper proportion between the front and rear sheets 12 and 14. A heated press, which includes a shaped die, is compressed on the framework material to create a seal between the edging of the outlet connection port 34 and the possible lower flange of the front and rear sheets adjacent to the edging, at the fixed station of the port seal 110 .

The fixed port, or outlet 30, comprises a plastic material and is injection molded from a composition of 40 percent FINA Z9450 of polypropylene copolymer and 60 percent of Shell Kraton G1652 styrene ethylene-butylene styrene thermoplastic delastomer. Due to the similarities between the composition of the material of the fixed port 30 and the material of the inner seal forming surfaces of the front and back sheet, it can be seen that the front and back sheets can be sealed to the border of the fixed port 34 using a substantially similar thermal sealing regime,. like the one used for the formation of permanent seals, and peripheral seals, which are described in greater detail below.

After the insertion and sealing of the fixed port 30 to the material of the container, the sandwich of the film framework is then indexed to a sacrificial port insertion station 112, where the sacrificial ports (72 and 74 in Figure 6) are insert between the front and back sheets, at positions along the first side of the container and connect with the locations that will become the first and second compartments 22 and 23. The sacrificial ports 72 and 74 are preferably injection molded from of a 100 percent polypropylene material but can also be manufactured from a material having a composition similar to the composition of the outlet port 30. In a manner similar to the outlet connection port 30, the front sheets and later are sealed to the sacrificial ports 72 and 74 along the bevelled piping 76, which are provided for such a purpose.

After the insertion of the sacrificial ports 72 and 74, the film material of the front and back sheet is coupled together by a permanent heat seal along a portion of the common peripheral flange 16 extending through which the upper part 18, the lower part 20, and a continuous side 28 of the finished container will become. Along the opposite side 27 of the container 10, the permanent thermal seal is provided parallel to, but spaced apart from, the peripheral sandwich flange 16 of interlaced film material, and is formed in an interrupted fashion along the desired flange of the film. Container finished just inside the common peripheral flange 16.

After formation of the perimeter seal of the perimeter sealing station 114, the material of the container is indexed to a first sealing station of the sacrificial port for the medicament 116. The material of the front and back sheet is sealed to the bevelled border 76 of the second sacrificial port 74 by compressing the material of the front and back sheet into the bevelled edge of the port by means of a pair of concave heat sealing dies. As is the case with the fixed port die, the heat seal die of the second medical sealing station or station 116 is formed in a conformational manner such that when the two halves of the sealing die are compressed together, they form a generally elliptical having a shape which is the image reflected in a mirror of the convex sealing and beveled surface of the second sacrificial port.

Then, the web material is indexed to a second, optional sealing station of the sacrificial port compartment 118, wherein the material of the front and back sheet of the container is compressed and thermally sealed to the bevelled border 76 from the sacrificial port of the first compartment 72. .

It is appreciated that the order of sealing of the sacrificial ports to the container is purely arbitrary and that the second sacrificial port sealing station 116 can easily follow the first sacrificial port sealing station 118 and vice versa. In addition, the sealing stations for sealing the sacrificial ports 72 and 74 to the container 10 may precede the perimeter sealing station 114. In addition, another optional sealing station, peelable seal forming station 120 which is depicted in Figure 7. following the insertion station 1 of the sacrificial port 110 preceding the perimeter sealing station 114, it is optionally provided to form peelable seals between the first side 27 and the second opposite side 28 of the container 10. The peelable seals are divided into two and subdivide 'container 10 into a diversity of compartments. Alternatively, the optional removable seal station 120 can be configured to proceed to the sacrificial port insertion station 112, only by relocating the peelable seal station along the path of the web material. It is evident that a variety of removable sealing stations can be provided, the container has to be manufactured with multiple compartments.

It is evident to someone skilled in the art that the sequential, but independent, diversity of sealing stations can be configured to operate automatically while the web material of the film is indexed to its respective stations. Alternatively, the sealing stations may be present in the container manufacturing machinery, but loaned inactive, in such a way that their particular seals are not formed in a specific production run. In particular, a container can be manufactured without any of the removable seals as will be described in greater detail below. After the application of the sacrificial port seals, the container's lattice material is indexed to an adjusted zone sealing station 122, which applies a permanent thermal seal to the meterial of the container that contacts and overlaps some of the interrupted seal stations. permanent along the common peripheral rim and extends to the rim of the film material of the container.

After the steps of the thermal sealing process, the container can be indexed through a hanging support piercing station 124 or something similar, which forms a hanging cutout in the upper center of the container. After stations 126 and 128 the containers are separated by cutting the web material at the lower end 20 (126) and then a top trimming station 128 cuts the material from the container at the upper end 18, after which the container is discharge of the manufacturing machinery 88 and the construction of the container is substantially complete.

It is obvious to someone skilled in the art that the number and configuration of compartments comprising the container is terminated only by the number and location of various thermal seals used to form the container. In addition, depending on the number of containers that are contemplated for the final product, an appropriate number of sacrificial ports are provided and placed along their respective truss rims. It is understood that the modular manufacturing process according to the present invention is adaptable to manufacture medical containers having a single primary compartment, or multiple compartment containers having any number of compartments, merely by providing additional removable seals and additional sacrificial ports in which fill the compartments. For each configuration of compartments and sacrificial ports, the zone seal cut-out press in the sealing station of the cut-out zone 122 can be properly reconfigured by removing one face of the press and replacing it with another, it is configured to provide one, three, four or whatever appears in channels or openings to connect a variety of sacrificial ports to a variety of compartments.

Similarly, it is clear to someone skilled in the art that the composition of the front and back sheets of the container can be changed to adequately replace the rolls of supply of web material for the film of the front and back sheets and with others suitable materials In particular, both the supply rolls of the front and back sheets can be of a single layer 80:20 so that the finished container is transparent on both sides. Due to the modular nature of the manufacturing apparatus, the application station of impediment for clearance at the aluminum foil application station can both become inoperable, such as the station for forming peelable seals, and therefore forming the machinery of making the container to provide a single compartment container that is completely transparent, which may comprise a variety of outlet connection ports, such as medicinal ports and separate fixed ports.

Accordingly, the container manufacturing machinery in accordance with the present invention is suitable for manufacturing a wide variety of medical containers, and having a wide variety of sizes, and a variety of sealing configurations and port locations. All containers thus manufactured will be seen as suitable for expansion so that they can expand their capacity and then for their aseptic filling in accordance with the principles of the present invention as well as suitable for use in combination with a terminal sterilization process, if such a thing is desired FORMATION OF THE SEAL The peelable seals 25 and 26 formed during the manufacturing process described above are straight line seals having a thin, rectangular shape. While they appear similar to conventional straight-line seals, the removable seals of this embodiment are improved in that they exhibit a more predictable rupture characteristic across the production lots, that is, they exhibit a characteristic of uniform resistance to the pressure of handling.

Without being limited by theory, it is believed that seal detachibility is achieved by limiting the time, pressure and temperature necessary to fuse the interconnection between the inner layers and the front and back blades having a lower melting temperature than the inner layers. intermediate and external layers of the posterior lamina. The depth of the structural alteration in the inner layers in the fusion zone is limited, therefore confers a removable character to the seal while providing sufficient strength to prevent a break in the normal handling of the container.

Preferably, the driving force for the container 10 of the present invention is closely controlled to provide container integrity under extreme driving conditions, although it is easy to activate for all users. This activation effort is characterized by a rupture pressure that is preferably about 1,800 more / less 0.450 kilos per centimeter (psi). However, this pressure can be increased slightly to accommodate the larger volumes associated with the enlarged containers described herein.

In order to achieve such uniformity in the breaking pressure of a generally rectangular seal, it has been determined that the critical parameter to be controlled is the temperature. The uniform response to breaking pressure can be achieved by controlling the sealing temperature within plus / minus -16.66 ° C. Commercially available heat sealing production apparatuses are not able to control variability in thermal seal temperature within this desired range. However, the thermal sealing time is able to be controlled very precisely. Consequently, the time is chosen as the control parameter and adjusted to compensate for the variation in the thermal seal temperature. The time and pressure of the sealing head is monitored to ensure that they are within the acceptable ranges described above and the thermal sealing time is adjusted accordingly. While the contact pressure is preferably in the range of about 230 psi to about 340 psi, it is recognized by someone skilled in the art that the pressure in the lower range of (approximately 230 psi) is provided for its convenience to locate the parameters of a thermal seal production machinery. As long as the pressure exerted by the heat seal bars in the material of the container is sufficient to force the layers of the seal material in contact over the surface gravity of the desired seal, a releasable seal is formed given an appropriate temperature and time. In fact, it has been experimentally determined that variations in temperature and time of heat sealing beyond those contemplated by the present invention result in seals that not only fail to exhibit desirable characteristic of uniform strength, but also fail to break completely at length of the seal. Incomplete rupture of the seal usually results in a residual diluent, for example, remaining trapped in 90 degree corners where the detachable dies come in contact with the permanent peripheral seals of the container. Accordingly, the diluent / drug mixture ratio may not be as expected, and the administration of the drug may be at a higher concentration than desired.

Examples of specific time, temperature and pressure settings forming peelable seals, in the 80:20 film of the illustrated embodiments, which have a burst pressure of approximately 4 +/- 1 psi include: pressure 235 psi, temperature = 125 ° C, and time = 1.9 seconds; and pressure = 235 psi, temperature = 128.3 ° C, time = 1.75 seconds.

The highest temperatures and pressures and associated times are used to provide the permanent peripheral thermal seals and the seal of the outlet connection port, which produce effects of alteration of the structure in a greater proportion to, or depth of, the sealing layers. Such seals can be formed by thermal sealing at a temperature of 143.3 ° C and a pressure of up to 200 psi for about 2 seconds. Those skilled in the art recognize that various techniques for forming both the permanent and available seals can be used in the construction of the container of the present invention. In particular, it is evident that by controlling the sealing temperature to a greater degree (within about +/- 16.66 ° C) they also allow the formation of peelable seals having a uniform breaking pressure. In addition, the stamp is chosen as the control parameter for the formation of stamps since it is capable of being precisely controlled. The precise control of temperature, pressure or both give the same result.

AGGREGATING THE COMPARTMENTS After the container 10 reaches the manufacturing stage exemplified in Figure 6, its volumetric capacity can be enlarged according to the principles of the present invention. In particular, any of the compartments 22, 23 and 24 can be expanded or otherwise enlarged to increase their volumetric capacity. For example, the first compartment 22 may be permanently expanded in order to increase the amount of diluent stored. This can be particularly advantageous where a lower dose of medicine is desired or where a higher concentration drug is used.

The first compartment 22 can expand by stretching either the front sheet 12, the back sheet 14, or both, outward from the common plane 70. This stretching elongates the film layers comprising the respective front or back sheets 12 and 14 both in the longitudinal and transverse directions. The compartments 22, 23 and 24 can be elongated or otherwise stretched in different proportions to accommodate variable increases in volumetric capacity.

For example, as best illustrated in Figure 6 in conjunction with Figure 6, the first compartment 22 can be expanded by temporarily applying a gas supply under pressure to the first sacrificial port 72. Pressurized gas inflates the first compartment. 22 and applies an expansion force on the surface area for one of the front and rear sheets 12 and 14. This force permanently stretches the materials of the front and back sheets 12 and 14. Preferably, the first compartment 22 is permanently stretched. or it elongates both in the direction of and the direction transverse by the pressurized gas to the desired volumetric capacity. To facilitate proper stretching and forming of the shape of each of the front and back sheets 12 and 14, an instrument or mold having shaped cavities can be used as described in greater detail below. The pressurized gas may include compressed air. However, other compressed gases or even liquids can be used. Preferably, the pressurization gas is 0.2 micron filtered air or nitrogen. Referring now to Figures 8-10, there is shown an alternative single-compartment embodiment of a flexible medical container constructed in accordance with the principles of the present invention. In this embodiment, as the characteristics of those of the previous embodiment are designated by similar reference numbers followed by the letter "a." As illustrated, a flexible container 10a can be provided for the combined administration and storage of a medicinal solution.

In this embodiment, the generally opposite front sheet 12a and back sheet 14a are sealed together along a substantial portion of a common peripheral flange 16a to form a single volumetric closure 17a. If desired, the volumetric closure 17a can be divided into two or more separate compartments using peelable seals extending from a first side 27a of the common peripheral flange 16a to a second opposite side 28a of the common peripheral flange 16a and releasably joining the sheets front and rear 12a and 14a as previously described.

A pair of separate separate sacrificial ports 72a and 74a can be supported along the first side 27a of the common peripheral flange 16 and an outlet connection port 30a can be supported along the lower part 20a. The ports 72a, 74a and 30a are placed between the front and rear sheets 12a and 14a along the interruptions in the permanent seal and are thermally sealed in place as previously described. The ports 72a, 74a and 30a are advantageously provided as part of this single-compartment container 10a to facilitate the enlargement of the volumetric closure 17a as well as its use with common manufacturing and handling equipment. Therefore, ports 72a, 74a and 30a and their manufacture can be identical to that previously described for the multi-compartment container.

The container 10a is manufactured in a conventional non-expandable size. In this stage of the manufacturing process, the container can be enlarged, or alternatively, it can retain its non-expanded volumetric closure as it was manufactured and proceed to an aseptic filling step. In the example of Figure 8, the container 10a can be manufactured having a substantially flat front sheet 12a constructed from a single layer of polymer as previously described and an opposite back sheet 14a of similar size constructed from a laminated material of multiple layers also as previously described. The opaque and transparent barrier layers previously described have been omitted. Without a compartment for a medication, these barriers of impairment are generally not necessary. However, these impediment layers can be added or otherwise provided that, as described below, a multiple compartment mode with an enlarged compartment or compartments is desired. The container 10a of Figure 8 suitably comprises a length that can be fabricated along the first and second sides 27a and 28a of approximately 20.95 centimeters and a width through the upper and lower portions 18a and 20a of approximately 13.33 centimeters. In this embodiment, the permanent seal along the common peripheral rim 16a can define a volumetric closure 17a with maximum planar dimensions of approximately 17.78 centimeters by approximately 8.90 centimeters. These dimensions are approximate and do not count for the open spaces between the sacrificial ports 72a and 74a and the volumetric closure 17a.

The described container 10a therefore provides a surface area 70a of approximately 62.23 square centimeters for each of the front and rear sheets 12a and 14a.

As manufactured, the single compartment container 10a has a particular volumetric capacity of approximately 130 to 150 milliliters. For the purposes of example only, this capability is defined simply by filling the volumetric closure 17a with a fluid and then measuring that amount in a graduated cylinder. However, a larger volumetric capacity may be desired within the rectangular limits of the described container. As discussed, the overall capacity of the container 10a can be greatly increased by stretching at least one of the front and back sheets of the volumetric closure 17a. This may include stretching each of the sheets 17a and 14a in a different amount. Preferably, the expanded front and back sheets 12a and 14a each extend outward or away from a common plane 71a, as best illustrated in Figure 9, each forming a curved surface as best illustrated in Figure 10. As used herein, the term planar, in relation to the front and back sheets 12a and 14a refers to the respective sheets before being enlarged.

In some applications you may wish to stretch only one of the front and back sheets 12a or 14a. In those cases the front sheet 12a is the most likely candidate for expansion. This is finally due to the fact that the backsheet 14 includes a layer of aluminum foil or similar impediment layer and necessarily has a lower modulus of elasticity generally extensible properties of lower response. Since the front sheet 12a is generally a homogeneous layer with more sensitive extensible properties, a greater stretch is achieved when the front sheet 12a is stretched on the back sheet 14a. In addition, backsheet 14a is commonly used for markings, include administration and mixing instructions. Printing may be less effective on a stretched and curved sheet. Reading the information printed on a permanently drawn curved sheet can also be difficult. However, in particular applications, the backsheet 14a can also be stretched exclusively.

Pertaining to the elongation of either the front sheet or the back sheet 12a or 14a, the container that is manufactured in accordance with the present invention, is in recognition that the elongation characteristics of the front and back sheets depend on the particular materials of which are manufactured. The extensible physical properties of the various single-layer and multi-layer laminated films used to build a medical container previously determined by the methods set forth in ASTM D-882-81 specification. The tyl extensible properties of the various components of the single layer and multilayer films described above are available from the film manufacturer by means of technical data sheets of the particular film. For example, KRATON G1652 styrene ethylene-butylene styrene elastomer has a tyl tensile strength of approximately 4500 psi, exhibits approximately 500 percent stretch at break, and a modulus of approximately 700 psi at 300 percent extension . Similarly, the Fina Z9450 copolymer has a tyl attraction force of approximately 2500 psi, while the aluminum foil layer (ALCAN 1145) has a tyl tensile strength of approximately 9300 psi (0.001 thickness) and a characteristic tyl elongation (at a thickness of 0.001) of approximately 4.2 percent. It is well understood by one skilled in the art that other films having different tensile strength and different elongation characteristics by necessity can be expanded to a correspondingly greater or lesser degree than the films referred to above. Such different elongation characteristics can be easily calculated with a resource with analysis data in uniform proportions of chin gap, uniform temperatures and uniform moldings of samples such as a sample cut of weights with an ASTM die.

Referring now to Figures 11-12, an embodiment of an instrument or form 130 in accordance with the present invention is described for use for enlarging the container 10a of the present invention. The instrument 130 is configured to receive at least a portion of the volumetric closure 17a. The instrument 130 includes an upper instrument portion 132 and a lower opposite portion of the instrument 134. In the illustrated embodiment, the lower portion of the instrument 134 has an internal cavity 136 and the upper portion of the instrument 132 has an opposite internal cavity 138. Planar external surface 140 surrounds each of the cavities except for an opening 142 in one of the ports 72a, 74a and 30a.

Other instrument configurations may include a portion of instruments 132 or 134 that is not provided with a cavity, but has a substantially planar surface. This configuration is advantageous when only one of the front and back sheets 12a and 14a is expanded. Other configurations include altering the size and shape of each cavity 136 and 138 to conform to the shape of the elongated front and rear sheets 12a and 14a.

The instrument 130 may include coupling devices 144, such as corresponding pegs and holes to ensure that the upper and lower portions of the instrument 132 and 134 remain stationary and interconnected during use. However, any other device or method can be used to retain the upper portions 132 and 134 aligned and together. A sealing flange 146 can circumferentially surround at least one of the cavities 136 and 138 and follow the sealing fingerprint of the compartment to be expanded. The sealing rim 146 holds the front sheet 12a and the back sheet 14a together during the expansion process and retains the pressurized gas within its limit. This prevents the inflation forces from substantially transferring into the permanent seal along the common peripheral flange 16a. Seal flange 146 may incorporate an o-ring or similar device may be provided in each portion of instrument 132 and 134 or alternatively, only one of the portions of the instrument. The sealed rim 146 is preferably broken or otherwise interrupted around the opening 142. This allows the pressurized gas in and out of the volumetric enclosure 17a. Preferably, the opening 142 is located adjacent one of the ports 30a, 72a or 74a to allow inflation and deflation through that port.

In the embodiment illustrated in Figure 11, the instrument 130 is configured to receive the volumetric closure in its entirety 17a from the single-compartment container 10a. The container 10a is placed in the lower portion of the instrument 134 with the outer surface of the front sheet 12a facing the lower cavity 136 and the common peripheral rim 16a held by the planar surface 140. The sealing boundary 146 is aligned just inside of the permanent seal along the common peripheral flange 16a. A pair of separate separate sacrificial ports slots 148 are disposed along a common side of each of the instrument portions 132 and 134 and each is configured to receive one of the sacrificial ports 72a and 74a. An output connection port slot 150 is disposed along a second common side of the instrument portions 132 and 134 is configured to receive the output connection port 30a.

Once the container 10a is aligned with one of the instrument portions 132 and 134, and preferably, to the lower portion of the instrument as described above, the opposing portions of the instrument can be brought together. The upper portion of the instrument 132 can be placed against the lower portion of the instrument 134 and aligned so that the outer surface of the back sheet 14a is facing the upper cavity 138 and the ports 30, 72a and 74a approach within the port slots 148 and 150. The planar surface 140 of the upper portion of the tool 132 sits against the planar surface 140 of the lower portion of the instrument 134 and restrains the common entire peripheral flange 16a with exception of the opening 142. Opening 142 allows passage of pressurized gas in and out of first sacrificial port 72a. The sandwich container 10a can now be inflated with the pressurized gas to inflate the volumetric closure 17a and forcibly expand the front and back sheets 12a and 14a against the cavities 136 and 138.

The instrument 130 may also be provided in any other number of configurations as can be determined by those skilled in the art and therefore, the exemplary embodiment is not intended to be limiting. Additional exemplary embodiments may include an instrument that has lower upper cavities of different size or a tool with a tool portion having a cavity and the opposite surface of the side 12a and 14a are stretched. Alternatively, the tool can have a variety of discrepant cavities to inflate with different compartments and flat surface sections in each of the instrument portions to hold the removable seals when only one compartment of a multi-compartment container is enlarged, for example, each portion of the instrument may include only a single cavity, of a size barely smaller than the external diameter of the compartments.

The sacrificial port slots 148 and the outlet connection port slot 150 can be configured to align the container 10a with the instrument 130. Therefore, notches can be included to receive the trims 78a and 80a at the sacrificial ports. 72a and 74a or have other configurations to locate each of the ports in a fixed manner. Alternatively, only one or two of the port slots 148 and 150 can be configured as such. However, other devices and methods may also be used to align the container 10 within the instrument 130 as is known to those skilled in the art. For example, the alignment ridges may be provided along the flat surface 140 to receive at least a portion of the top, bottom or side portions 18 a, 20 a, 27 a, and 28 a of the container 10 a. alternatively, a slot, set by another alignment device (not shown) can be provided in the container 10 a and a complementary alignment post or whatever looks like it can be provided in the instrument 130.

In a preferred embodiment, the instrument 130, with the captured container 10 a, is driven by an expansion machinery 150 for inflation and enlargement, as best illustrated in Figure 13. Preferably, the expansion machinery 152 includes a table or base of operations 154 for receiving and operating the instrument 130. The instrument 130 is then placed in the mouthpiece 156 of the machinery 152. Once inside the machinery 152, the cylinders 157 are used to clamp or otherwise have the opposite portions of the instrument 132 and 134 together. The cylinder 157 can be hydraulic, driven by an electric motor, and something similar, but preferably is pneumatic. Other devices and methods such as pressure cuttings can also be used together to the halves of the instrument during the expansion process.

A pressurized gas supply 158 is coupled to the opening 142 within the instrument 130 and the container 10a is inflated with the pressurized gas 158 to fully expand the front sheet 12 a and the lower cavity 136 and the back sheet 14 a in the cavity rear 138. This expansion permanently stretches and permanently elongates both the front sheet and the back sheet 12 a and 14 a outwardly from the common plane as defined by the peripheral rim 16 within the instrument 130. The pressurized gas 158 can be maintained within the instrument 130 for a short period of time to maintain the front and back sheets 12 a and 14 a against the respective cavities 136 and 138. By keeping the volumetric enclosure 17 a in inflated state it reduces the amount of shrinkage or elastic rebound. Typically, the film construction materials previously described, this period is less than one minute. The pressurized gas 158 can then be released, the tool 130 can be removed from the expansion machinery 152 and the enlarged container 10 a can be removed from the instrument 130. Preferably, this expansion operation is automated.

In the illustrated embodiment, the container 10a expands from an initial capacity of volume or non-enlarged capacity from about 130 to 150 ml at an enlarged volume capacity of about 250 to 300 ml as the volume capacity is defined herein. Preferably, the container 10 a is enlarged to a volume capacity of about 260 to 280 ml and more preferably about 280 ± 5 ml. To achieve these particular final dimensions in a single compartment container exemplified in Figure 8, the upper and lower cavities of the instrument 136 and 138 are configured to have a printing area corresponding to the compartment area of the container, i.e. about 17.80 cm X about 8.90 cm, each is hollowed out to a sufficient depth to define a volume of about 300 ml for the lower cavity 136 of the instrument a volume of about 100 ml for the upper cavity 138 of the instrument. Specifically, a lower cavity of the instrument 136 is hollowed out to a depth of approximately 3.80 cm, while the upper cavity 138 of the instrument is hollowed out to a depth of approximately 1.27 cm. Furthermore, on the sides of each of the cavities a continuous curvature is combined in the lower part of the cavity to minimize any rigid "corner" in which the material of the container can be forced, therefore, by canning the material.

Therefore, the opposing cavities of the instrument 136 and 138 when combined together, have a total volume of about 400 ml of a longitudinal cross-sectional area of about 62.23 cm2. These volumes and areas are not strictly accurate, because the regions within port slots 148 and 150 have not necessarily been taken into consideration. It should also be noted that due to the greater depth of the lower cavity of the instrument 136 (and its consequent increased volume), the front sheet 12 a is allowed to stretch to a considerably greater degree than the back sheet 14 a. The reason for the difference in volume capacity between the upper and lower cavities of the instrument is because the materials of the front and back sheets expand until they contact the internal surfaces of the cavities.

The depth of each space and its corresponding volume are configured to correspond to the extensible properties typical of the film to be expanded in that cavity.

The volumetric enclosure 17a is preferably inflated with compressed air, having a pressure of between about 10 and 30 psi for about 1 to 30 seconds. Pressures less than 10 psi can be used, however, the force that develops is generally not sufficient to permanently stretch the front and back sheets 12 a and 14 described against the cavity. The use of different materials, such as a container having two homogeneous layers similar to the single-layer front sheet that is described 12 a, which may allow an effective stretch at 10 psi or less. Pressures of about 30 psi and above tend to rapidly expand the front and back sheets 12 a and 14 a against cavities 136 and 138. This rapid expansion can stretch the material too fast which can lead to a wrinkled material, to delaminations inside the backsheet of the laminated product 14 a and other undesirable defects. It may be possible to use higher pressures by slowly or gradually inflating the volumetric enclosure 17 a in steps or alternatively, by heating the compressed gas. The sheet to be expanded or the surfaces of the cavity can also be heated. These and other methods and devices can be used to modify the preferred pressures and times necessary to achieve the desired enlarged capacity of the container 10 as is known to those skilled in the art.

In a preferred embodiment, the volumetric enclosure 17 a is inflated within the instrument 130 described using compressed air regulated at a pressure of between about 15 and 25 psi for about 15 and 25 seconds. More preferably, the pressure is regulated at about 20 psi and maintained for approximately 15 seconds at room temperature. By increasing the pressure or time, you can further stretch each of the films if the volumetric capacity of the expansion instrument increases correspondingly. Certainly, this increased expansion provides an increased volume of expanded container. Similarly, decreasing pressure or time results in reduced expansion and lower volume capacities. These preferred parameters expand the front sheet 12 a fully against the lower 300 ml cavity 136 and the back sheet 14 a fully against the upper 100 ml cavity 138 and result in an overall enlarged capacity of approximately 280 ml +/- - 5 ml. The shrinkage due to the material relaxation module results in an enlarged capacity of the container 10 to being smaller than the combined volume of the cavities 136 and 138. In order to minimize a greater shrinkage, an unlocking process can be used as described below in more detail.

The described exemplifying process of enlargement results in the surface area of the front sheet 12 a being enlarged by approximately 10% and the back sheet 14 a enlarging by approximately 6%. However, the preferred materials may be capable of permanently deforming to much greater amounts, allowing the manufacture of the containers to have even greater volume capacity. For example, the surface area of the front sheet 12 to which the preferred material 80:20 is comprised, can be enlarged to approximately at least 16% while the surface area of the backsheet 14 to the preferred laminate material, It can be enlarged to approximately 10%. The surface area of the front sheet 12 a, which comprises the preferred material 80:20 can be enlarged more than the surface area of the back sheet 14 a preferred due in part to the low elasticity of the aluminum layer in the structure of the Laminated material of the backsheet.

Once the 10 a container has been enlarged, it is unlocked. This procedure maintains the volume of a gas within the enlarged volumetric closure 17 sufficiently to maintain the enclosure of an expanded condition. Unlocking prevents the enlarged volumetric closure 17 a from contracting further due to the inherent elasticity of the materials as defined by their relaxation modules. This can be particularly advantageous for the front sheet 12 to which it typically expands to a greater elongation and is not supported by an adhered layer of aluminum.

The unlocking includes inflating the container 10a with a low pressure gas to ensure that the volumetric closure 17 a is fully expanded to the enlarged configuration. The low pressure gas may comprise compressed air regulated to a few psi. However, other gases such as dry nitrogen can also be used. Preferably, the release pressure is regulated to less than about 10 psi, and more preferably to between about 1 and 5 psi. This prevents a continuous shrinkage, fatigue in the seals and something similar. Once the volumetric closure 17 a has been fully expanded, the sacrificial ports 72 a and the outlet connection port 30 a are sealed with a plug. In a larger contraction of the volumetric enclosure 17 a finds a resistance in the form of gas pressure inside the sealed volumetric enclosure 17 a. the unlocking can take place within the expansion machinery 52. However, an unlocking station can be provided preferably.

A further embodiment of a medicinal container made with an expanded compartment volume is now described with reference to Figures 6, 11 and 12. Figure 6 is a semi-schematic front view of a particular embodiment of a multi-compartment container thereto. stage of the manufacturing process as the single compartment container illustrated in Figure 8. The multi-compartment container of Figure 6 differs from the single compartment container embodiment in that the expandable seals 25 and 26 encompass the container and they extend between the permanent peripheral seals 16 on any of the sides of the container, to define an intermediate compartment 23 to contain, for example, a medicament. The removable seals 25 and 26 also function to delineate a separate compartment 22 for containing a liquid diluent an outlet compartment 24 that is initially empty. A multi-compartment container according to the embodiment of Figure 6 made with the films and techniques described above is capable of maintaining a relatively limited volume of a liquid diluent in the diluent compartment 22. The backsheet of the multilayer laminate is a material of barriers of relatively rigid impediment as mentioned above, whose rigidity limits the volume of the diluent and can be introduced into the diluent compartment 22 to approximately 60 ml, in fact, the containers of the type illustrated in Figures 1 and 6 they are commonly manufactured as 50 ml containers, that is, they contain 50 ml of a liquid diluent to be mixed with a drug before administration. The efficacy of various inclusion therapies commonly requires IV containers capable of sustaining a volume substantially greater than that of approximately 60 ml volume of the diluent compartment 22 of the container of Figures 1 and 6. Specifically, a PAB container manufactured and sold by McGraw, Inc. of Irvine, California is commonly used to maintain 100 ml of a 0.9% sodium chloride solution, in a condition called partial filling. Therefore, it can be seen that expanding the diluent compartment 22 of a multi-compartment container as illustrated in Figures 1 and 6 is particularly desirable.

As described above, in connection with the embodiment of Figure 8, the container is confined within the instrument having an inner hollow cavity or cavities and is inflated with a pressurized gas to thereby stretch the front and back sheets (alternatively, the front sheets only) to permanently expand the particular volumetric capacity of the compartment. The process and apparatus described in connection with Figures 9-13 are equally suitable for use and connection with the multi-compartment container of Figure 6. All that is required is that the printing of the area of the upper and lower cavities 136 and 138 are reduced, or modified to conform to the printing of the diluent compartment 22 of the multi-compartment container 10 of Figure 6.

The printing of the diluent compartment, as this term is used herein, is generally rectangular in shape and is defined, on three sides by a permanent peripheral seal 16 and, on the fourth side, by a removable seal 25 separating the compartment diluent 22 of the drug compartment 23. By ignoring the channel 41 between the diluent compartment 22 and its corresponding sacrificial port 72, the impression of the compartment describes a rectangle that is approximately 8.90 cm wide and approximately 12.7 cm long. Accordingly, the sealing limit (146 of Figure 11) is configured and sized to conform to the seal impression of the diluent compartment 22 between the multi-compartment container of Figures 1 and 6.

Because the seal 25 that separates the diluent compartment from the medicament compartment is a removable seal, particular care must be taken to ensure that the sealing limit (146 of Figure 11) is set to remain slightly within the seals, particularly the removable seal 55. When remembering that the removable seal is designed to break under pressure, it is recognized that by providing the sealing boundary 146 within the sealing impression and particularly within the impression of the removable seal 55 , forms a pressure stop against the application of a rupture pressure to the peelable seal.

In a manner similar to that described in connection with the embodiment of Figure 8, the diluent compartment 22 of the multi-compartment container of Figures 1 and 6 can be expanded by stretching either the front sheet 12, the back sheet 14 or both . Due to the characteristics of the films used to form the front and back sheets, 12 and 14, it is understood that the front sheet 12 is expandable to a greater degree than the back sheet 14 under the same time and pressure regime as described. in connection with Figure 8.

The embodiment of the instrument for the expanding use of the diluent compartment of a multi-compartment medical container is generally somewhat similar to one embodiment of the instrument described in connection with Figures 11 and 12. However, due to the smaller area impression ( 8.90 cm X 12.7 cm opposite to 8.90 cm X 17.78 cm) of the diluent compartment against the total container, the depths of the upper and lower cavities 136 and 138 are correspondingly reduced, so that the film materials of the film are not overstretched. Diluent compartment. As described above, the lower cavity 136 has an impression of approximately 8.90 cm X 12.7 cm and a cavity depth of approximately 0.191 cm approximately 2.54 cm to define the cavity volume from approximately 160. ml to approximately 175 ml.

Preferably, only the front sheet is stretched in the embodiment of Figure 6 so that the upper portion of the instrument comprises a substantially flat surface that is not provided with the cavity. Nevertheless, where a cavity is to be provided, it should have an impression of approximately 8.90 cm X 12.70 cm and a cavity depth of approximately 0.63 cm approximately 0.89 cm to define the volume of the cavity from approximately 50 ml to approximately 60 ml. By providing priorities in such a manner, it allows the diluent compartment 22 to expand from its conventional 50 ml nominal capacity to an approximate volumetric capacity of 100-150 ml, as the term has been previously defined.

Once the multi-compartment container of Figures 1 and 6 has been arranged with an appropriate inflation instrument, the diluent compartment is inflated through its corresponding sacrificial port (72 of Figure 6) by air or filtered nitrogen from 0.2 microns at an inlet pressure of approximately 20 psi. The diluent compartment is kept in an inflated condition for about 15 seconds to allow time for the film to stabilize in its stretched condition. After volumetric expansion, the multi-compartment container is now ready to be sterilized, aseptically filled, trimmed to its final dimensions and shipped to the final consumer.

STERILIZATION, FILLING AND FINAL FORMATION OF THE CONTAINER After the container 10a has been enlarged to the desired capacity or volume capacities, it preferably has the configuration exemplified in Figure 8. The container 10 a is now in a condition for sterilization and aseptic filling with a medicinal solution. After sterilization and filling, sacrificial ports 72 a and 74 a can be removed, leaving an enlarged finished container as best illustrated in Figure 17.

In an exemplary filling process, the particular embodiment of the container to be filled, in accordance with the invention, is one that incorporates a single-layer front sheet film 12 a, a laminated aluminum foil product of multiple layers of the the back sheet 14 a. the front and back sheets 12 a and 14 a have been formed to comprise a volumetric container 17 a having a portion of the common peripheral rim 16 a which is left unsealed to be filled through the sacrificial ports respectively provided 72 a and 74 a. this container mode 10 a in this manufacturing step is best described in Figure 8. The primary manufacture of the container, including the supply of an outlet connection port 30 a and the sacrificial ports 72 a and 74 a, is achieved by the method and apparatus previously described.

In order for an aseptic filling process to be accepted for medical purposes, the empty container 10a must be provided in a sterile condition. Conventionally, sterilization of the container takes place in a separate processing area or facility due to rather the extensive and complex equipment and processes that are required for the sterilizing material. A particular undesirable characteristic for the sterilization process is that the container must be transported to the sterilization facility for processing, after which the sterility of the container must be maintained during transportation and storage subsequent to an aseptic filling installation. The container should be introduced into the aseptic filling zone by means of a sterile transfer in order to prevent contamination of the aseptic zone by the container. Once it is introduced into the aseptic zone, the container can be filled aseptically, but it must also be handled in a sterile way.

In accordance with the practice of the principles of the invention, following the primary manufacture of the container, a variety of empty containers are loaded into the handling container and then sealed to protect the flexible containers 10 from contents within the environmental contamination.

After now looking at Figure 14, a transport or handling container, generally indicated at 160 and called 'a conveyor' here functions as a transportable insulator of sterile content for the sterilization, transport and introduction into the aseptic zone, of the empty containers in In a systematic manner, the conveyor 160 comprises three components: a generally rectangular containing tray 162, a sealable film cover 164, and a rail cartridge 166 for having a variety of containers 10 within the tray that are described in greater detail in FIG. The described conveyor 160 is only an exemplary embodiment but other configurations can also be used as is known to those of skill in the art.

The generally rectangular containment tray 162 can be constructed of a thermally formed polystyrene material or other material capable of withstanding several sterilization cycles without significant degradation. The tray 162 may be formed generally in the form of a basin with its upper peripheral flange bent over outwardly to form a horizontally oriented flat peripheral lip or a piping 168 extending beyond the sides of the tray 162 at a distance from about 0.63 cm to about 2.54 cm. Preferably, the edge 168 extends up to about 1.90 cm beyond the sides of the tray, but any extension that provides rigidity to the tray 162 and a surface for holding a seal is adequate. Two opposing bags 170 and 172, are formed in approximately the centers of the two short opposite sides of the tray and extend outward from the plane of the short sides .. The bags 170 and 172 extend only and partially downwards along from the sides of the tray and thus form two opposite beads which the ends of the rail cartridge 166 can be inserted. The rail cartridge 166 rests on the inner surface of the bags 170 and 172 and is therefore suspended above the bottom of the tray 162 at a height sufficient to allow the containers 10 to be exposed in the rail cartridge so that they are handled freely inside the volume of the tray. Accordingly, the bags 170 and 172, in combination with the cartridge 166, function to maintain a variety of containers 10 a. in a specific orientation during UV transport, storage and sterilization.

Once the rail cartridge 165 is loaded with the containers 10a and inserted into the bags 170 and 172, the tray 162 is environmentally sealed by thermally sealing the cover of the plastic film 164 to the rim or edge of the tray 168 in a different orientation. For the illustrative purposes of Figure 14, the film cover 164 is illustrated in the middle of the sealing process, with a portion of the lid raised to show the rail cartridge 166 that is nested within the tray 162. The cover Film 164 is placed in the edging around the perimeter of the tray. In an exemplary embodiment, the plastic film cover 164 is constructed to have dimensions that allow the film cover to be placed in the edging of the tray 168 such that the rim of the film cover is inserted from the flange. of the border of the tray around the total periphery of the edging. In addition, the thermal seal of the film cover is applied to extend beyond the flange of the film cover 164, to ensure that no portion of the edge of the film cover which would create a 'seal' is left unsealed. flap "with loose edges The orientation of the film cover, the placement and evasion of the loose edges is particularly important for the ultraviolet (UV) decontamination process of the surface carried out in the transport system 160 when the system transport is introduced into the aseptic zone.The openings, caused by loose edges of the film cover and / or flaps can cause a localized shadow, when exposed to UV radiation, whose shading effect can overcome the UV effect of the process decontamination.

Once the film cover 164 has been thermally sealed to the rim of the tray 168, the transport system defines a hermetically sealed environment that functions to isolate the contents of the external contamination. The conveyor 160 can then be placed in a multi-bag envelope or similar cover (not shown), which acts as a "dust cover", and is identified with an adhesive label that is placed in the envelope.

Referring now to Figures 15 and 16, a rail transporting cartridge 174 may comprise a plurality of injection-turned polystyrene T-bars 176 arranged at spaced intervals to thereby form longitudinally running grooves 178 there in between. The manufactured containers 10 a can be loaded into the cartridge 174. The containers 10 a such as those described in Figure 8, are charged to the rail transporting cartridge 166 by inserting their sacrificial ports 72 a and 74 a into the slots 178. which are formed between the T-rails of the cartridge 176. The T-rails 176 may have edges that separate apart at a sufficient distance (approximately 13.0 mm) such that the central filling barrel of each sacrificial port 72 a and 74 a it is able to fit there in the middle, and adapt to link the sacrificial ports between the circumferential edges of the port (78 a and 80 a) such that the container 10 a is grasped by two trimmings of the T-rail 176 below its higher border of the circumferential sacrificial port 80 a.

In the embodiment of the rail transport cartridge described in Figures 15 and 16, four slots 178 are provided to receive the containers 10 a, with the containers loaded in the rail cartridge 166 in alternating left-right orientations. The sacrificial ports 72 a and 74 a of each container 10 a are inserted in two of the slots 178. A first container can be loaded in the first and fourth slots and oriented in a first horizontal direction. A second container can then be loaded into the rail cartridge 166 with its sacrificial ports 72 a and 74 a inserted in a first and third slots of the cartridge 178. The second container that is loaded in a second horizontal direction oriented 180 ° with respect to the first container . Other containers 10 a are loaded in the rail transporting cartridge 166 in a similar manner, with the horizontal orientation of the container alternating from left to right; the sacrificial ports of the containers oriented to the left are inserted in a second and fourth slot, the fixed ports of the containers oriented to the right are loaded in a first and third slot, as described above, until the carrier cartridge Rail 162 is completely full. Obviously, each conveyor holds a large number of pre-enlarged containers that larger containers.

After loading, the rail transporting cartridge 174 is placed inside the tray 162 with the ends of the T-rails 176 nested in the bags 170 and 172 that are formed at the ends of the tray. The bags 170 and 172 hold the rail transport cartridge 166 within the volume interior of the tray and provide additional side support that prevents the cartridge from moving around during shipping, sterilization and storage.

The sealed conveyor, which includes the empty containers inside, is wrapped in a similar container multiple bag for radiation sterilization where the conveyor 160 and the retained containers 10a become sterile in an E-ray sterilization process or something similar . After loading the carriers and the preceding E-ray sterilization process is completed, the sterile medicinal containers 10 can be filled aseptically with a medicinal solution. This may include transporting conveyor 160, and retained containers 10 a to an aseptic filling station. The filling of the volumetric closure 17 a can be achieved using the related request technique codependent 08/837, 927 filed on April 11, 1997, the description of which is incorporated herein for reference. These techniques can be applied to a single medicinal solution or alternatively for the filling of multiple compartments.

After sterilization and filling, the manufacture of the enlarged container of Figure 8 can be completed by removing the sacrificial ports 72 a and 74 a and completing the permanent seal around the first side 27 a of the common peripheral flange 16 a. The finished container 180 includes an increased capacity to store a medicinal solution relative to the conventional, non-enlarged container.

The final manufacturing process includes removing a portion of the first side 27 a from the container 10 just inside the sacrificial ports 72 a and 74 a and includes the sacrificial ports. Each of the fluid connections or passageways between the sacrificial ports 72 a and 74 a of the volumetric enclosure 17 a are then sealed. This is carried out by applying a permanent seal, similar to that previously described, through the first side 27 to just inside the common peripheral flange 16. This permanent seal completes the volumetric closure 17 a. When a multi-container compartment is used, the permanent seal can be applied through each sacrificial port 72 a and 74 a after each respective filling. A portion of the first side 27 a that includes the sacrificial port 72 a and 74 a can then be removed. As can be seen in relation to the differences between Figures 8 and Figure 17, the removed portion includes the sacrificial ports 72 a and 74 a and a narrow band of the first side 27 a of the container 10 a. For those skilled in the art they recognize that in the primary discussion of the embodiments comprising a liquid diluent and a single powder medicament as well as a single volumetric closure modality do not limit the scope of the invention. The use of liquid medicaments in the intermediate compartment or a variety of compartments for liquid or powdered medicaments, to be mixed with the diluent, can be employed using the present invention. The multiple sacrificial ports and the communication channels between the sacrificial ports and the respective compartments can easily be in accordance with the practice of the principles of the invention. Moreover, depending on the susceptibility of any of the components that comprise the compartments of the multiple compartments to moisture or. contamination of free oxygen, those compartments that are protected by additional applications of a clear and transparent high-barrier laminate containing SiOx on the front sheet of the container in those regions of the compartment. Such highly hindered laminate products can be provided with or without be combined with a detachable detachment of a laminated aluminum foil product containing a barrier of high hindrance.

The above descriptions of the exemplary embodiments of sterile and flexible containers are for illustrative purposes. Due to the variations that are apparent to those skilled in the art, the present invention does not intend to be limited to the particular embodiments described above. Such variations, and other modifications and alterations are included within the scope and intent of the invention as described in the following claims.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers. Having described the invention as above, property is claimed as contained in the following:

Claims (17)

1. CLAIMS A flexible container for the combined storage and administration of a medicinal solution, characterized in that the container comprises: a flexible front sheet having a first relaxed state defining a first surface area; a flexible backsheet, having a first relaxed state that defines a first surface area equal to the surface area of the flexible front sheet, the front and back sheets are sealed together along a common peripheral rim to form an enclosure volumetric that defines a first volume capacity; Y wherein at least one of the front or back sheets is permanently deformed in a second stretched state defining a second surface area greater than the first surface area to define a second volume capacity greater than the first volume capacity.
2. 2. The flexible container, as defined in accordance with claim 1, characterized in that both the front and rear sheets are permanently deformed in a second stretched state, the front and rear sheets project out of a common plane.
3. 3. The flexible container, as defined in accordance with claim 2, characterized in that the permanent deformation of the front and rear sheets forms with the volumetric closure to define a second volume capacity at least twice that of the first volume capacity.
4. 4. The flexible container, as defined in accordance with claim 3, characterized in that the front sheet comprises a polypropylene-polyethylene copolymer combined with a styrene-ethylene-butylene styrene elastomer.
5. 5. The flexible container, as defined in accordance with claim 4, characterized in that the polypropylene-polyethylene copolymer is mixed with the styrene-ethylene-butylene styrene elastomer in a proportion of about 80% -20% w / w.
6. 6. The flexible container as defined in claim 5, characterized in that the backsheet comprises a multi-layered laminated product that includes: an inner layer of a polypropylene-polyethylene copolymer blended with a styrene-ethylene-butylene styrene elastomer in an approximate ratio of 80% -20% w / w; an intermediate layer of aluminum foil; Y a thermoplastic outer layer that has a higher melting point than this inner layer.
7. 7. A flexible container as defined in claim 6, characterized in that it also comprises at least one port that is disposed between the front and rear sheets and that defines a fluid communication path to the interior of the volumetric enclosure.
8. 8. A flexible container as defined in claim 7, characterized in that the front and back sheets are permanently deformed in a second stretched condition by the introduction of a fluid under pressure in the volumetric enclosure through the port.
9. 9. A flexible container as defined in claim 8, characterized in that the pressurized fluid is a gas.
10. 10. A flexible container as defined in claim 9, characterized in that the pressurized fluid is introduced with air into the volumetric confinement at an inlet pressure of about 15 to about 25 psi and is maintained at this inlet pressure for a time from about 15 to about 25 seconds.
11. 11. A flexible container as defined in claim 10, characterized in that the inlet pressure is regulated to approximately 20 psi and maintained at this regular pressure for approximately 15 seconds.
12. 12. A flexible container as defined in claim 8, characterized in that the pressurized fluid permanently deforms the front and back sheets to thereby expand the volumetric confinement from a first volume capacity in the range of approximately 130 to approximately 150 milliliters. at a second volume capacity in the range of about 250 to about 300 milliliters.
13. 13. A flexible container as defined in accordance with claim 12, characterized in that the volumetric closure is expanded to a second volume capacity of approximately 280 milliliters +/- 5 milliliters.
14. 14. A flexible container as defined in claim 8, characterized in that the front sheet is permanently deformed to a second stretched state characterized by a second surface area greater than the first surface area by an amount of about 16%.
15. 15. A flexible container as defined in claim 14, characterized in that the backsheet is permanently deformed in a second stretched condition characterized by a second surface area greater than the first surface area by an amount of up to 10%.
16. 16. A flexible container as defined in accordance with claim 15, characterized in that, in addition, it comprises at least a second port disposed between the front and rear sheets and forming a fluid communication path to the interior of the volumetric enclosures.
17. 17. A flexible container for the storage and combined administration of drugs and diluents for IV solutions, characterized in that the container comprises: a substantially transparent front sheet having a first surface area that is constructed from a flexible planar layer of a polymer film; a backsheet having a second surface area that is constructed from a flexible planar layer of a laminated product, the backsheet is hermetically joined to the front sheet along a common peripheral rim to form a volumetric enclosure; a first releasable seal extending between the first side of the common peripheral rim and a second opposite side of the peripheral rim and releasably attaching the front sheet and the back sheet to form a first compartment for containing a diluent; a second removable seal extending between the first and second opposite side of the common peripheral rim and releasably attaching the front sheet and the back sheet to form a second compartment for containing a medicament and a third exit compartment, the second compartment being between the first compartment and the exit compartment; and an outlet connection port that is supported by a common peripheral flange and fluidly connects to the exit compartments; wherein at least a portion of the front sheet covering the first compartment is permanently stretched to increase the capacity of the first compartment 18. A flexible container as defined in claim 17, characterized in that, furthermore, it comprises a diluent port supported by the common peripheral flange and fluidly connected to the first compartment. 19. A flexible container as defined in claim 18, characterized in that, furthermore, it comprises a medicinal port supported by the common peripheral rim and fluidly connected to the second compartment. 20. A flexible container as defined in claim 17, characterized in that the front sheet comprises a copolymer of polypropylene-polyethylene blended with a thermoplastic elastomer of styrene ethylene-butylene styrene. 21. A flexible container as defined in claim 17, characterized in that the front sheet is permanently stretched from a substantially flat surface. 22. A flexible container as defined in accordance with claim 17, characterized in that the backsheet comprises: an internal layer of a polypropylene-polyethylene copolymer blended with a styrene-ethylene-butylene-styrene thermoplastic elastomer, the inner layer opposing the front sheet; an intermediate layer of aluminum foil; Y an external thermoplastic layer that has a higher melting point than the inner layer. 23. The flexible container as defined in claim 22, characterized in that the front sheet comprises a copolymer of polypropylene-polyethylene • blended with styrene-ethylene-butylene styrene thermoplastic elastomer in an approximate ratio of 80% / 20% w / w. 24. The flexible container as defined in claim 22, characterized in that it also comprises a substantially clear film of a barrier laminate product sealed to the front sheet, the protective laminate film covers the second compartment. 25. The flexible container as defined in claim 24, characterized in that it also comprises a high barrier protective opaque film removably sealed to the clear film of a laminated product, the opaque film is sized to cover the clear protective film and the second compartment. 26. A method for increasing the capacity of a flexible container for the storage and administration of a medicinal fluid; characterized in that the method comprises the steps of: providing a flexible container having a flat, flexible front sheet as opposed to a flat, flexible back sheet along a common plane, the front sheet being hermetically attached to the flexible back sheet; along a common peripheral rim to form a volumetric enclosure having a port; Y expand the volumetric closure to permanently stretch at least one of the front or rear sheets to thereby increase the capacity of the volumetric closure. 27. The method as defined in accordance with claim 26, characterized in that the expansion step comprises inflating the volumetric confinement with a pressurized gas. 28. The method as defined in claim 26, characterized in that the expansion step comprises the steps of: maintaining the backsheet and the common peripheral rim substantially against the common plane; and inflate the volumetric closure with a pressurized gas to permanently stretch a portion of the front sheet out of the common plane. 29. The method as defined in claim 26, characterized in that the expansion step comprises inflating the volumetric confinement with a pressurized gas to permanently stretch both the front and back sheets. 30. The method as defined in accordance with claim 29, characterized in that the stretched volumetric closure holds a volume capacity of at least twice the container provided. 31. A method for constructing a flexible container for the combined storage and administration of a medicinal solution, characterized in that the method comprises the steps of: providing a substantially transparent front sheet and constructed from a flexible planar layer of a polymer; providing a flexible backsheet constructed from a vapor impermeable layer; sealing the front sheet and the back sheet together along a common peripheral rim to form a volumetric enclosure; provide a port supported by the common peripheral flange fluidly connected to the volumetric enclosure; Y expand the volumetric closure to permanently stretch at least one of the front or back sheets to thereby increase the capacity of the volumetric closure. 32. The method as defined in claim 31, characterized in that the expansion step comprises inflating the volumetric closure with a pressurized gas to permanently stretch both the front and back sheets. 33. The method as defined in claim 31, characterized in that the expansion step comprises the steps of: maintaining the backsheet and the common peripheral rim against a substantially planar surface; and inflate the volumetric closure with a gas pressure, 34. The method as defined in accordance with claim 33, characterized in that the step of maintaining the backsheet and the common peripheral rim comprises: providing a multi-piece instrument configured to receive the volumetric closure, the instrument includes a lower portion of the instrument and an upper portion of the instrument, the lower portion of the instrument has a flat bottom surface and the upper portion of the instrument has a concave upper surface with a flat flange and is configured to capture the common peripheral flange against the flat bottom surface; Y placing the container inside the instrument where the backsheet contacts the flat surface of the lower portion of the instrument and the front sheet faces the concave surface. 38. A method for forming a flexible container for the storage and combined administration of IV solutions, characterized in that the method comprises the steps of: providing a substantially transparent front sheet constructed from a flexible planar layer of a polymer film; providing a flexible, vapor impermeable backsheet constructed from a multi-layer flat laminate; sealing together the front sheet and the back sheet along a common peripheral edge to thereby define a volumetric closure; providing a first sacrificial port supported by the common peripheral flange and connected fluidly to the volumetric enclosure; providing a second sacrificial port supported by the common peripheral rim and fluidly connected to the volumetric confinement, the second sacrificial port is separated from the first sacrificial port along a first plane of the common peripheral rim; providing an outlet connection port fluidly connected to the volumetric confinement, the outlet connection port is supported by a second side of the common peripheral rim; holding the volumetric closure in an instrument having a first concave region to receive at least a portion of the front sheet and a second concave region opposite to receive at least a portion of the back sheet, the first concave region defines a greater volume than the second concave region; expanding the volumetric closure with a pressurized gas to stretch the front sheet and the back sheet against the respective concave regions of the instrument; Y relieve pressure gas inside the volumetric enclosure; wherein the front and rear sheets are permanently stretched to thereby increase the volume capacity of the container. 39. The method as defined in claim 38, characterized in that the step of providing a front sheet comprises a polypropylene-polyethylene copolymer layer blended with a styrene ethylene-butylene styrene thermoplastic elastomer. 40. The method as defined in claim 39, characterized in that the step of providing a backsheet comprises providing: an inner layer of polypropylene-polyethylene copolymer blended with a styrene-ethylene-butylene styrene thermoplastic elastomer, the inner layer being opposite to the front sheet; an intermediate layer of aluminum foil; Y a thermoplastic outer layer that has a higher melting point than the inner layer. 41. The method as defined in accordance with claim 40, characterized in that, further, it comprises the steps of: fill the volumetric closure permanently stretched with a gas; seal the sacrificial ports with a plug; Y Seal the outlet connection port with a plug to keep the container in the expanded configuration. 42. The method as defined in accordance with claim 41, characterized in that, further, it comprises the steps of: providing a transport vector that includes a rail cartridge configured to receive and hold a variety of containers, with the rail cartridge the containers are crimped by their respective sacrificial ports; load a variety of containers in the rail cartridge; place the loaded rail cartridge on the transport vector; seal the transport vector against environmental contamination; Y sterilize the sealed transport vector and the loaded containers by applying a radiation beam. 43. The method as defined in accordance with claim 42, characterized in that, further, it comprises the steps of: remove each of the sacrificial ports; Y complete the sealing along the first side of the common peripheral rim inwards of the sacrificial ports, where the formation of the container is complete. 44. The method as defined in claim 40, characterized in that the step of expanding the volumetric enclosure comprises permanently stretching the front and back sheets to increase the volume capacity of the pre-enlarged container at least twice. 45. The method as defined in claim 44, characterized in that the step of expanding the volumetric enclosure comprises enclosing the volumetric confinement within the instrument at a pressure of between about 15 and 25 psi. 46. The method as defined in accordance with claim 45, characterized in that the pressurized gas is compressed air. 47. The method for forming a flexible container for combined storage and administration of drugs and diluents for IV solutions, the method comprises the steps of: providing a flexible and substantially transparent front sheet constructed from a flat layer of a polymer; providing a flexible and vapor impermeable backsheet constructed from a flat multilayer laminate; sealing the front sheet and the back sheet together along a portion of a common peripheral rim to define a volumetric closure; heating the front and back sheets in a first located area to fuse together the front and back sheets along the first heated localized area, therefore a first peelable seal is formed which extends between the first side of the common peripheral flange and a second opposite side of the peripheral rim, the first removable seal removably attaches the front and back sheets to thereby form a first compartment within the volumetric closure to contain a diluent; providing a first sacrificial port between the front and back sheets and in fluid communication with the first compartment; expanding a portion of the volumetric enclosure forming the first compartment to permanently stretch the front sheet and the back sheet to thereby increase the volumetric capacity of the first compartment. 48. The method as defined in claim 47, characterized in that it further comprises the steps of: heating the front and back sheets of a second localized area to fuse together the front and back sheets along a second heated localized area, to thereby form a second peelable seal extending between the first side and the second side opposite the common peripheral rim, the second peelable seal separately joins the front and back sheets to thereby form a second compartment for containing a medicament and a exit compartment, the second compartment is between the first compartment and the exit compartment; providing a second sacrificial port interposed between the front and back sheets, and in communication with the second compartment; Y provide an exit port interposed between the front and rear sheets and in communication with the exit compartment. 49. The method as defined in claim 48, characterized in that the step of providing a front sheet comprises providing a polypropylene-polyethylene copolymer layer blended with a styrene ethylene-butylene styrene thermoplastic elastomer. 50. The method as defined in accordance with claim 49, characterized in that the step providing a backsheet comprises providing a multilayer laminate product having: an internal polypropylene-polyethylene copolymer layer blended with a styrene ethylene-butylene styrene thermoplastic elastomer, the inner layer opposite the front sheet; an intermediate layer of aluminum foil; and a thermoplastic outer layer having a higher melting point than the inner layer. 51. The method as defined in claim 50, characterized in that the step of inflating comprises inflating the volumetric confinement within an instrument at an approximate pressure of between about 15 and about 25 psi for about 10 and 25 seconds. SUMMARY A flexible container (10) is provided for the storage and administration of medical solutions. The container incorporates a transparent front sheet (12) made of a flat layer of a polymer, and an opposing back sheet (14). The backsheet is made of a flat layer of a laminated product. The front and back sheets are sealed together along a common peripheral edge (16) to form a volumetric closure (17). The volumetric enclosure is constructed from materials that have properties of high impediment to oxygen and moisture that allows the thermoplastic container to be stored for long periods of time without degrading the contents. Then the volumetric enclosure is inflated with a pressurized gas to permanently stretch out the front and back sheets, and thereby increase the volumetric capacity of the container. An alternative embodiment of the container incorporates multiple compartments (22, 23, 24) that are separated by detached seals (25, 26) to contain a diluent, and a medicament. The seals are broken by handling the container to thereby mix the containers together for administration to the patient by a conventional IV configuration.