MXPA01007158A - Gamma-irradiation sterilized polyethylene packaging - Google Patents

Abstract

Articles of product material in gamma-irradiated packaging, wherein the gamma-irradiated packaging contains polyethylene. Polyethylene has been shown to possess characteristics which are both unexpected and superior to those suggested by historical literature. Articles of the invention are particularly suited to oxidation-sensitive product materials and medicinal products. Methods of producing such articles are included.

Description

PACKAGING IN POLYETHYLENE STERILIZED BY IRRADIATION GAMMA TECHNICAL FIELD The invention in general relates to sterilized packages and, in particular, the invention relates to the use of polyethylene in the packaging of product materials for use with sterilization by gamma irradiation.

BACKGROUND INFORMATION Gamma irradiation is often used as a sterilization technique for food, medical devices and medicinal products, as well as their respective packaging, that is, some form of container. This is particularly true in the case of plastics, where sterilization techniques that require heat may exceed the softening, or even the melting point of the plastic. Other sterilization techniques using aqueous or gaseous sterilizers may also be inadequate, due to related contamination or the like. Gamma irradiation is usually carried out in one of two ways. A first method is to locate an article by a source of radiation, typically a radioactive isotope of cobalt or cesium. The radiation source is commonly housed in steel casings, which are kept in a water reservoir to absorb the gamma radiation while not in use. The articles that will be subjected to the irradiation are placed near the water tank and receive the gamma irradiation when the covers are lifted out of the tank. A variation on this method is to pass the article through the radiation source using a conveyor. A second method is to focus a beam of radiation directly on an article. This sterilizing unit typically contains a housing for containing the radiation source, a concentration chain for concentrating the radiation to a more localized region, and an output of the beam. Articles for sterilization are passed through the concentrated radiation, typically using a conveyor. In any irradiation method, exposure to radiation is determined by the intensity of the radiation source or beam and the exposure period. While gamma irradiation has its advantages over other forms of sterilization, it also has detrimental effects. The irradiation of plastics results in energy transfer that is not spatially or molecularly specific in the polymer. Two main chemical reactions are presented as a result of this energy transfer: 1) the cross-linking of the polymer chains and 2) the cleavage or breaking of the bonds that result in the creation of free radicals. BioMedical Polymers, Metals, and Composites, ch. 44, pp. 1001-18, "Ionizing Radiation's Effects on Selected Biomedical Polymers," Skiens, W. E. and Williams, J.L. (Technornic Publishing Co., 1983) (hereinafter "Radiation by -Ionization"). Both reactions can occur simultaneously, and the predominant reaction is regulated if the polymer degrades (cleaves) or increases in molecular weight due to polymerization (crosslinking). The degradation products of the radical-induced reactions resulting from the cleavage may consist of low molecular weight compounds (including evolution of gases), unsaturation sites in the polymer chain (often the cause of discoloration), and peroxy species (which can extract hydrogen to form hydrogen peroxides) in the presence of oxygen. Radicals resulting from irradiation can have a long life and result in subsequent irradiation effects. These radicals can be trapped in the irradiated polymers and react for extended periods of time; The reaction rate depends on the reactivity of the sample and the characteristics of the mass transfer of the system. Oxidative reactions normally lead to cleavage, and cause deterioration in the polymer's mechanical properties. Free radicals produced by irradiation in oxygen-containing environments, for example, air, often quickly become radicals per oxi dice. Additives are often used to reduce the harmful effects of polymer irradiation. These types of additives are often called antirads. The antirads can either directly reduce the damage by radiation absorption and avoid interaction with the polymer, or indirectly reduce the effects of the damage by combining easily, with the free radicals generated by radiation in the polymer. Antirads often also act as antioxidants.

The effects of gamma irradiation on polymers have been studied extensively. See, for example, Thayer, Donald W., Chemical Changes in Food Packaginq Resulting from Ionizing Irradiation, Food and Pa cka gin g In t era ct i ons, chap. 15 (1988) (hereinafter "Chemical Changes"); Killoran, John J., Chemical and Physical Changes in Food Packaging Materials Exposed to Ionizing Radiation, Ra di a t i on Res. Rev. , vol. 3, pp. 369-388 (1972) (hereinafter "Chemical and Physical Changes"); Ionizing Radiation. Killoran notes that the radiation stability of plastic films can be related to the total amount of gaseous products involved as a result of ionization radiation treatment. Chemical and Physical Changes, p. 376-77. As noted above, the evolution of gaseous products is an indicator of cleavage degradation. Killoran also notes that experimentation classifies plastic films in order to decrease radiation stability, based on these criteria related to excision, such as polyethylene terephthalate > polystyrene > polyiminoundecyl > poly (vinyl chloride vinyl chloride) > polyethylene. Id. in 377.

The main interest for the pharmaceutical industry is the oxidative degradation of aqueous and oil-based formulations packed in plastic containers sterilized by gamma irradiation. For many medicinal products packaged in plastic containers, sterilization may be required either before or after filling. Free radicals produced as a result of cleavage during irradiation of the polymeric container often lead to oxidative degradation of the medicinal product in contact with the polymer. The oxidative degradation of a medicinal product can result in lower potency of the active ingredient, reduced efficacy of the formulation, significant levels of impurities, unacceptable physical properties of the formulation, shorter product shelf life and subsequent monetary losses related to the Reduced shelf life. Although product safety is necessary for both food and pharmaceutical products, the requirements for an irradiated packaging material for pharmaceutical products are stricter than those for packaging materials irradiated for the food industry. Oxidative processes that can be tolerated or ignored in food applications can be unacceptable in the pharmaceutical industry, with respect to the product of the food industry, mainly qualitative and subjective (organoleptic, ie, the pleasant taste of food, taste, consistency, color, smell, etc.) while for the product of the pharmaceutical industry are quantitative and objective. The criteria for the packaging materials for foods to be irradiated consist primarily of 1) without significant negative change in any of the important physical / mechanical characteristics of the packaging material (which may include firmness, tensile strength, breaking strength, hardness / flexibility, resistance to solvents / light / moisture / etc.) and 2) that the packaging material does not contaminate the food with the compounds produced by the irradiation. "Safe to be used after irradiation" is the main regulatory criterion for packaging materials proposed for use in food substances treated with radiation. See, for example, 21 CFR 179.45 (E.

OR . , 1998), Packaging Materials for Use During the Irradiation of Prepackaged Foods. The requirements for pharmaceutical products are that they are safe, effective and consistently have known characteristics that can be measured or quantified, such as potency, strength and purity. These requirements are currently regulated by various laws. Even minor changes to physical properties, chemical or biological of pharmaceutical products (to the extent that they can be caused or can be initiated by contact with irradiated packaging materials) can, and often do, render the medicinal product inadequate or unsafe for use alleged. For example, irradiated packaging for pharmaceutical products should not stimulate a loss of potency of the active ingredient even minimal (less than 10% for antibiotics) with respect to the shelf life of the product which is often two to five years. Accordingly, it is not reasonable or prudent to assume that simply because a material is acceptable for irradiated food substances in the packaging, it will be an acceptable packaging material for a pharmaceutical product with respect to the total shelf life of the pharmaceutical product. For the reasons mentioned above and for other reasons mentioned below, which will be apparent to those skilled in the art at the time of reading and understanding this specification, there is currently a need for suitable polymeric packaging materials to be used with product materials after of sterilization by gamma irradiation, and methods for using these polymeric materials for packaging.

BRIEF DESCRIPTION OF THE INVENTION The problems mentioned above with the polymeric irradiation and the packaging of the product materials and other problems are treated by the invention. For simplicity, the product materials can be referred to simply as materials. Studies on stability of antibiotics packaged in polymeric packaging materials sterilized by gamma irradiation indicate results inconsistent with expectations. Predictions based on radiation stability of various polymers suggest that polyethylene could be lower than various polymers to protect oxidation-sensitive materials from oxidative degradation after gamma irradiation, ie polyethylene could be expected induces increased levels of oxidative degradation with respect to other various polymers. However, the studies set forth herein reveal that some kinds of polyethylene are unexpectedly superior in their ability to protect materials from oxidative degradation after gamma irradiation. Skiens and Williams show that considerable segmentation of the carbon-carbon bond occurs in polyethylene at the time of irradiation. Ionizing Radiation, p. 1006. While oxidative degradation in general is related to free radicals resulting from cleavage, one would expect polyethylene to offer only marginal protection against oxidative degradation due to the considerable cleavage that results from gamma irradiation. Accordingly, the ability of polyethylene to protect materials against oxidative degradation, as set forth herein, is greater than expected.

The invention can be applied to all materials that require gamma irradiation or a gamma-irradiated packaging for storage, transport or use. These materials include medicinal products. Medicinal products are those substances used to prevent or treat diseases, injuries or pain. Medicinal products may have applications in humans or animals. Accordingly, pharmaceutical products and veterinary products are suitable for use with the invention. The invention can also be applied to materials sensitive to oxidative degradation. As used herein, a material is sensitive to oxidative degradation, or is sensitive to oxidation, if the material suffers from low potency of an active ingredient, reduced efficacy of the formulation, higher levels of unacceptable impurities for the properties Physical properties of the formulation, shorter shelf life of the product or monetary loss as a result of contact with the peroxidized radicals induced by irradiation. The main examples include anti-infective agents such as antibiotics, anti-fungi and anti-virals. However, drugs sensitive to oxidation in all classical pharmaceutical categories are well known. These categories include, but are not limited to: antihistaminic drugs, laxatives, vitamins, decongestants, gastrointestinal painkillers, antacids, anti-inflammatory substances, antimanias, coronary vasodilators, peripheral vasodilators, cerebral vasodilators, psychotropics, stimulants, antidiarrheal preparations, anti-angina drugs, vasoconstrictors, anti-coagulants, anti-thrombotic, analgesic, antipyretic, hypnotic, calming, antiemetic, growth stimulators, anti-nausea, anti-convulsant, neuro-muscular drugs, hyperglycemic and hyperglycemic agents, thyroid preparations and ant i-thyroid, diuretics, cytotoxic, ophthalmic, antispasmodic, uterine relaxants, anti-obesity drugs, anthelmintics, hormones, vaccines, mineral additives and nutritional supplements and more. Another category of materials of special interest is that which is composed of biopharmaceutical products manipulated by genetic engineering that have special packaging needs to protect them from oxidative degradation.

Within the family of antibiotics noted above, the classes of cephalosporins, 1 -inosamides, quinolones, oxazolidinones, tet racicl inas, penicillin, and penicillin derivatives are of special interest, although most antibiotics are considered to be sensitive. to oxidat In particular, the inventcan be applied for use with pirlimycin, ceftiofur, lincomycin, neomycin, penicillin G and novobiocin. In additto the active medicinal ingredients sensitive to oxidat other non-active constituents of pharmaceutical formulat (products), such as vehicles and excipients may suffer from oxidative degradatat the time of exposure to the irradiated packaging materials. The oxidative degradatof a vehicle and / or excipient in a pharmaceutical formulat even if the drug itself is not oxidized, could produce formulat with unacceptable characteristics before the end of the shelf life of the formulat These unacceptable properties could include a poor ability to re-suspend the suspens difficult ability of the formulatto be applied with a syringe, unpleasant product odor, color or taste, and reductof the preservative act Formulat that have a constituent sensitive to oxidatwill be considered sensitive to oxidatas a whole. Polyethylene-containing packaging materials used in various embodiments of the inventmay contain one or more additives incorporated with the polyethylene. These additives include, but are not limited to: fungal release agents, stabilizers, antioxidants, antirads, mixing agents, lubricants, glidants, dyes and copolymers. Preferably, polyethylene is the predominant constituent in the packaging material. While other polymers can be added to polyethylene as copolymers without departing from the scope of the invent it should be recognized that these addit may result in higher levels of induced oxidative degradatof the product material due to the inclusof these other polymers in the packaging material. As used herein, a packaging material is in contact with a product material if it is in direct physical contact with the product material. A packaging material is also in contact with a product material if the radicals induced by irradiatof the packaging material are free to migrate to a surface of the product material, for example, through a semipermeable member. In one embodiment, the inventprovides a method for packaging a material. The method includes depositing the material in a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc. The method further includes exposing the container to gamma irradiat wherein the exposure of the container to gamma irradiatoccurs in at least one selected time from the group consisting of before depositing the material in the container, during deposit of the material in the container. and after depositing the material in the container, furthermore where the exposure of the container to gamma irradiatis presented at a temperature for environmental process greater than about 4 ° C. In another embodiment, the inventprovides a method for packaging a medicinal product. The method includes depositing the medicinal product in a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc. The method further includes exposing the "container to gamma irradiat wherein the exposure of the container to gamma irradiatoccurs in at least one selected time of the group consisting of before depositing the medicinal product in the container, during the depositof the medicinal product in the container and after depositing the medicinal product in the container., the invention provides an article. The article includes a material and polyethylene in contact with the material, wherein the polyethylene has a density greater than about 0.925 g / cc, in addition where the polyethylene is exposed to gamma irradiation in at least one selected time from the group consisting of of contacting the material and after contacting the material, still further where the polyethylene is exposed to gamma irradiation at an environmental process temperature greater than about 4 ° C. In a still further embodiment, the invention provides an article. The article includes a material and a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc, in addition where the material is deposited in the container. The container is exposed to gamma irradiation in at least a selected time of the group consisting before depositing the material in the container, during depositing the material in the container and after depositing the material in the container, in addition where the container is stored. exposes to gamma irradiation at an environmental process temperature greater than about 4 ° C. In still another embodiment, the invention provides an article. The article includes a medicinal product and a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc, in addition where the medicinal product is deposited in the container. The container is exposed to gamma irradiation in at least a selected time of the group consisting of before depositing the medicinal product in the container, during the deposition of the medicinal product in the container and after depositing the medicinal product in the container.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is an elevation view of a radiation source and an article according to one aspect of the invention, Figure 2 is a plan view and elevational view of an article according to another aspect. of the invention Figure 3 is a plan view and elevational view of an article according to a further aspect of the invention Figure 4 is an elevational view of an article according to a still further aspect of the invention. Figure 5 is a sectional view of one embodiment of a mixing vessel according to the invention, Figure 6 is a sectional view of another embodiment of a mixing vessel according to the invention.

DETAILED DESCRIPTION OF THE INVENTION In the following detailed description of the invention, reference is made to the appended drawings that form a part of the present and in which are shown, by way of illustration, specific embodiments in which the invention can be practiced . In the drawings, similar numbers describe practically similar components in all the various views. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be used and structural, logical, and other changes may be made without departing from the scope of the invention. Therefore, the following detailed description should not be taken in a limiting sense, and the scope of the invention is defined solely by the appended claims, together with the full scope of equivalents to which these claims are entitled. Polyethylene is commonly divided into classes based on its density. Commonly used classes include low density polyethylene (LDPE), medium density polyethylene (MDPE) and high density polyethylene (HDPE). This list of classifications should not be considered as a standard or a complete list of classifications. It is provided simply to focus the next exposure. Given these preferred approximate classifications, the characteristics of the polymer vary among the multiple producers of a given class of polyethylene, "or among the multiple grades of a class determined by a producer." Furthermore, what for a producer is called LDPE could be considered as MDPE by another producer In spite of these variations, some generalizations can be made Table 1 lists the typical values for some physical, mechanical and thermal properties of LDPE as used herein.

Table 1 Table 2 lists the typical values for some physical, mechanical and thermal properties of MDPE as used herein.

Table 2 Typical properties of medium density polyethylene Table 3 lists the typical values for some physical, mechanical and thermal properties of HDPE as used herein. The HDPE may further include high density polyethylenes beyond the density range of 0.941-0.97 g / cc listed here as typical.

Table 3 Stability studies were conducted using an aqueous formulation of pirlimycin packaged in containers comprising a variety of polymeric materials sterilized by gamma irradiation. These polymers represented seven different types of functional monomers. The polymeric materials included polystyrene (PS), polycarbonate (PC), polyester (PET), acrylonitrile / butadiene / styrene (ABS), poly (styrene acrylonitrile) (SAN), Nylon 66, LDPE, HDPE and polypropylene (PP) . The test was done by filling the aqueous pirlimycin in the containers, where the containers were exposed to gamma irradiation before depositing the material in each container. The expectation based on the historical literature was that the polymers that underwent the most excision could provide a less compatible packaging material than those that experienced more crosslinking. Some known ratios of cleavage to crosslinking are: Polypropylene = 0.5 (high degree of cleavage) Polyethylene = 0.3 Polystyrene = 0 (low degree of cleavage) The radiation doses needed to produce significant damage, ie, degradation due to the cleavage processes, for these polymers are: Polypropylene = 10 Mrad Polyethylene = 100 Mrad Polystyrene = 1000Mrad Although the evolution of volatile organic compounds is lower in higher density polyethylenes, LDPE and MDPE they can withstand significantly more irradiation than HDPE before experiencing equivalent degradation of physical properties. As an example, LDPE and MDPE can withstand approximately "100 Mrad or more of irradiation before undergoing equivalent elongation under tension as with HDPE irradiated at about 10 Mrad. Crosslinking predominates over cleavage in polyacrylic esters, polyacrylic acid, polyacrylamide, butadiene-acrylonitrile copolymers and styrene-acrylonitrile copolymers In general this is also true for aliphatic polyamides, ie Nylon 66. Polymers containing aromatic rings as a functional group in the monomer, ie polystyrene, polycarbonate and polyester, in general, are also more resistant to radiation-induced degradation than polyolefins, ie polyethylene and polypropylene, since cleavage has been linked to the production of radicals and that cleavage is related to degradation of mechanical properties, the relative amount of radiation necessary for prov The degradation of mechanical properties was used to classify polymers in their ability to protect the product from oxidative degradation. Of the polymers tested, the preliminary classification in general was as follows, where it was expected that the polypropylene would have at least the capacity to protect the product against oxidative degradation: PS, PC, PET, ABS, SAN, Nylon 66 >; LDPE, HDPE > PP Unexpectedly, the studies for experimental stability using the aqueous formulation of pirlimycin in the container sterilized by gamma irradiation produced an inconsistent classification very different from the accepted literature. Based on its ability to protect the aqueous formulation of. pirlimycin oxidative degradation, polymers are classified as follows, wherein the product packed in SAN suffered the highest level of oxidative degradation. HDPE > PC > Nylon 66 > PS > PET > PP > LDPE > ABS > SAN As noted above, there are differences among the multiple producers of a given class of polymer. Therefore, in cases that have multiple producers for a given class of polymer, averages of data were used to determine the classification.

The previous results were supported by similar stability studies performed in an aqueous formulation of another lincosamide antibiotic. The results were further supported by stability studies performed on two formulations of cephalosporin antibiotics, ie, ceftiofur hydrochloride with oil base and crystalline suspensions of ceftiofur acid-free. In all cases, containers containing predominantly higher density polyethylene than 0.925 g / cc showed acceptably low levels of oxidative degradation induced in the product material. Figure 1 illustrates a known sterilization system that can be used in the present invention. The sterilization system 100 has a radiation source 10 to produce gamma radiation 20 and may also include a conveyor 90 for passing the articles through the gamma radiation 20. The radiation source 10 can produce the gamma radiation 20 in all directions ( not shown) or can focus the gamma radiation 20 towards a more localized area as shown in Figure 1.

The article 50 includes a bottle 70 with a lid 60 surrounding the material 80. The bottle 70 and the lid 60 can be referred to in combination as a container. Although the article 50 is represented as a bottled material in this embodiment, the article 50 can take the form of any three-dimensional container surrounding the material 80. Furthermore, although the material 80 is represented as a liquid in this embodiment, the material 80 can take any physical form, including, but not limited to: solution, solid, gas, powder, granule, tablet, gel, suspension, paste or other physical form. The solutions and suspensions may be aqueous, oil-based or other solvent-based compositions. At least one component of the container, for example, the lid 60 and the bottle 70, contains polyethylene. The polyethylene is of the MDPE or HDPE classification, thus having a density greater than approximately 0.925 g / cc. A preferred range of polyethylene density is from about 0.926 to 0.97 g / cc. A more preferred range of polyethylene density is from about 0.941 to 0.97 g / cc. In one embodiment, the polyethylene is in contact with the material 80. In another embodiment, the polyethylene is a predominant constituent of the container. The article 50 is placed in the gamma radiation 20 on the conveyor 90. The article 50 can be moved through the gamma radiation 20 in a continuous manner, or it can be stopped within the gamma radiation 20 for a period of time. The exposure to a given intensity of the radiation source 10 can be regulated by controlling the speed of the carrier, or the period of the pause within the gamma radiation 20. It is expected that the invention can be better applied at radiation dose levels of up to 100 kGy (10 Mrad). A preferred range of irradiation dose levels is from 15 to 100 kGy (1.5 to 10 Mrad). A more preferred range of irradiation dose levels is from 15 to 60 kGy (1.5 to 6.0 Mrad). A still more preferred range of irradiation dose levels is from 25 to 60 kGy (2.5 to 6.0 Mrad). While the invention can be applied in addition to all environmental process temperatures within the limits of polyethylene processing, a preferred range of environmental process temperatures is greater than about 4 ° C. A most preferred environmental process temperature is about 25 ° C. The ambient process temperature is the temperature at which the article is exposed to gamma irradiation, and does not reflect any anticipated temperature rise of the article, product material or packaging material due to the absorption of incidental radiation The material 80 is deposited in the container using packaging techniques well known in the art, as will be recognized by one of ordinary skill in the art., the techniques for packaging depend on the nature of the material to be packed, the nature of the container in which the material will be packed, and the quality restrictions on the finished item. The invention, however, does not depend on the packaging technique used. Material 80 can be deposited in the container before gamma irradiation as shown in Figure 1. Alternatively, bottle 70 and cap 60 can be exposed to gamma irradiation before receiving material 80 in a manner similar to that is depicted in Figure 1. This gamma irradiation of the containers or their components is often used in conjunction with an aseptic filling operation well understood in the art where it may be desirable to avoid the gamma irradiation of an already sterile material. Gamma irradiation before and after filling can also be used with the invention. While not generally considered common in manufacturing practice, gamma irradiation can be further utilized with the invention during the packaging of the material 80 in a container. Further, although Figure 1 represents the gamma radiation 20 radiating from the above article 50, the invention does not depend on the angle of incidence of the gamma radiation 20. The gamma radiation 20 can radiate the article 50 from any angle as the gamma radiation 20 is expected to pass through article 50. Furthermore, although Figure 1 represents a radiation source 10 that radiates article 50, the invention can equally be applied to the use of multiple sources of radiation 10. Figure 2 represents another embodiment of an article 50 according to the invention. Article 50 is represented as a blister product in this modality. Article 50 includes a support 260 and. a blister 270 surrounding the material 80. The material 80 is represented as tablets. The backing 260 and the blister 270 may be referred to in combination as a container. At least one component of the container, i.e., backing 260 and blister 270, contains polyethylene. The polyethylene is of the MDPE or HDPE classification. In one embodiment, the polyethylene is in contact with the material 80. In another embodiment, at least one component of the container, i.e., the backing 260 and the blister 270, is predominantly polyethylene. Backing 260 often contains a polymer-free portion, such as a portion of metal foil in a composite film commonly used in these packaging configurations. In one embodiment, a polymer portion of the backing 260 contains polyethylene. In a further embodiment, a polymer portion of the backing 260 is predominantly polyethylene. Figure 3 represents another embodiment of an article 50 according to the invention. The article 50 is represented as a product in the form of a bag in this mode. The article 50 includes a first side 360, a second side 370 and seal portions 305 that surround the material 80. The material 80 is represented as a liquid. Seal portions 305 may extend further around the perimeter of article 50 depending on whether article 50 is formed from a polymer tube (as shown), a single polymer sheet (with seal portions extending around three edges, not shown) or two polymer sheets (with seal portions extending around four edges, not shown). The first side 360 and the second side 370 can be referred to in combination as a container. At least one component of the container, i.e., the first side 360 and the second side 370, contains polyethylene. The polyethylene is of the MDPE or HDPE classification. In one embodiment, the polyethylene is in contact with the material 80. In another embodiment, at least one component of the container, i.e., the first side 360 and the second side 370, is predominantly polyethylene. Figure 4 represents a further embodiment of an article 50 according to the invention. The article 50 is represented as a syringe product in this embodiment. The article 50 includes a plunger 460, a barrel 465, a cannula 470 and a lid 475 surrounding the material 80. The material 80 is represented as a liquid. The plunger 460, the barrel 465, the cannula 470 and the lid 475 can be referred to in combination as a container. At least one component of the container, i.e. plunger 460, barrel 465, cannula 470 and cap 475, contain polyethylene. The polyethylene is of the MDPE or HDPE classification. In one embodiment, the polyethylene is in contact with the material 80. In one embodiment, at least one component of the container, i.e., the plunger 460, the barrel 465, the cannula 470 and the lid 475, is predominantly polyethylene. In another embodiment, the 465 barrel is predominantly polyethylene. The invention is not limited to the use of containers or their components that consist simply of polyethylene. Commonly, additives are found in commercial polyethylenes. Some additives include, but are not limited to: fungal release agents, stabilizers, antioxidants, antirads, mixing agents, lubricants, glidants, dyes and copolymers. In addition to the additives, the containers according to the invention can also be mixing vessels. Two examples of containers for mixing are shown in Figures 5 and 6. Figure 5 depicts a portion of a container wall showing the material 80 in contact with a 505 polyethylene layer. The 505 polyethylene layer is predominantly polyethylene, although It may contain additives as noted above. The polyethylene layer 505 is in contact with the layer 515. The layer 515 can be used together with the polyethylene layer 505 to improve the structural integrity of the mixing vessel., to improve the physical characteristics of the container for mixing or to reduce the overall cost of the container with respect to one made exclusively of polyethylene. The layer 515 may be of any composition according to the above-mentioned objects. Common compositions include metals for improved structural integrity, waterproof glass and cardboard for reduced cost. Figure 6 depicts a portion of a container wall showing the material 80 in contact with a semi-permeable layer 625. The semi-permeable layer 625 is in contact with the polyethylene layer 605. The polyethylene layer 605 is predominantly polyethylene , but may contain additives as noted above. The semi-permeable layer 625 protects the polyethylene layer 605 from physical contact with the material 80, but is permeable to the radicals induced by irradiation in the polyethylene layer 605 in such a way that the radicals induced by irradiation are free to migrate through. of the semi-permeable layer 625 towards a surface of the material 80. Accordingly, the polyethylene layer 605 is in contact with the material 80 as defined above.

CONCLUSION The articles of the product material have been exposed in the packaging irradiated by gamma, where the container irradiated by gamma contains polyethylene. Polyethylene has shown to have characteristics that are both unexpected and superior to those suggested by historical literature. The articles of the invention are particularly suitable for materials of medicinal products and products sensitive to oxidation. The methods for producing these articles are further discussed. All publications, patents and patent applications are incorporated herein by reference. While in the above specification this invention has been described in connection with certain embodiments thereof, and many details have been shown for purposes of illustration, it will be apparent to those skilled in the art that the invention is amenable to additional embodiments and that Certain details described herein may vary considerably without departing from the basic principles of the invention. As an example, the invention is suitable for a wide variety of containers, including but not limited to: bottles, flasks, mastitis syringes, prescription syringes, ampoules, bags, blisters, cylinders, tubes, drums, buckets, cans and more. Therefore, it is clearly intended that this invention be limited only by the claims and equivalents thereof.

Claims (54)

1. CLAIMS 1. A method for packaging a material, comprising: depositing the material in a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc; and exposing the container to gamma irradiation, wherein the exposure of the container to gamma irradiation occurs in at least one selected time from the group consisting of before depositing the material in the container, during depositing the material in the container and after depositing the material in the recipient, in addition where the exposure of the container to gamma irradiation occurs at an environmental process temperature greater than about 4 ° C.
2. 2. The method according to claim 1, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of up to about 100 kGy.
3. 3. The method according to claim 1, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of about 15 to 60 kGy.
4. 4. The method according to claim 1, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of about 25 to 60 kGy.
5. 5. The method according to claim 1, wherein the polyethylene further has a density of about 0.926 to 0.97 g / cc.
6. 6. The method according to claim 1, wherein the polyethylene further has a density of about 0.941 to 0.97 g / cc.
7. 7. The method according to claim 1, wherein the polyethylene is in contact with the material after depositing the material in the container.
8. 8. The method according to claim 1, wherein the exposure of the container to gamma irradiation is further presented at an environmental process temperature of about 25 ° C.
9. 9. The method according to claim 1, wherein the material is sensitive to oxidation.
10. 10. A method for packaging a medicinal product, comprising: depositing the medicinal product in a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc; and exposing the container to gamma irradiation, wherein the exposure of the container to gamma irradiation occurs in at least one time selected from the group consisting of before depositing the medicinal product in the container, during the deposition of the medicinal product in the container and after depositing the medicinal product in the container.
11. 11. The method according to claim 10, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of up to about 100 kGy.
12. 12. The method according to claim 10, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of about 15 to 60 kGy.
13. 13. The method according to claim 10, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at a dose of about 25 to 60 kGy.
14. 14. The method according to claim 10, wherein the polyethylene further has a density of about 0.926 to 0.97 g / cc.
15. 15. The method according to claim 10, wherein the polyethylene further has a density of about 0.941 to 0.97 g / cc.
16. 16. The method according to claim 10, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at an environmental process temperature greater than about 4 ° C.
17. 17. The method according to claim 10, wherein the exposure of the container to gamma irradiation comprises exposing the container to gamma irradiation at an environmental process temperature of about 25 ° C.
18. 18. The method according to claim 10, wherein the medicinal product is sensitive to oxidation.
19. 19. The method according to claim 10, wherein the medicinal product is an anti-infective agent.
20. 20. The method according to claim 19, wherein the anti-infective agent is an antibiotic.
21. 21. The method according to claim 19, wherein the anti-infective agent is an antibiotic selected from the group consisting of cephalosporins, lincosamides, quinolones, oxazolidinones, tet raciclins, penicillin and penicillin derivatives.
22. 22. The method according to claim 19, wherein the anti-infective agent is an antibiotic selected from the group consisting of pirlimycin, ceftiofur, lincomycin, neomycin, penicillin G and novobiocin.
23. 23. The method according to claim 10, wherein the polyethylene is in contact with the medicinal product after depositing the medicinal product in the container.
24. 24. An article, which includes: a material; and polyethylene in contact with the material, wherein the polyethylene has a density greater than about 0.925 g / cc, in addition where the polyethylene is exposed to gamma irradiation in at least one time selected from the group consisting of before contacting the material and after contacting the material, still further where the polyethylene is exposed to gamma irradiation at an environmental process temperature greater than about 4 ° C.
25. 25. The article according to claim 24, wherein the polyethylene is exposed to gamma irradiation at a dose of up to about 100 kGy.
26. 26. The article according to claim 24, wherein the polyethylene is exposed to gamma irradiation at a dose of about 15 to 60 kGy.
27. 27. The article according to claim 24, wherein the polyethylene is exposed to gamma irradiation at a dose of about 25 to 60 kGy.
28. 28. The article according to claim 24, wherein the polyethylene further has a density of about 0.926 to 0.97 g / cc.
29. 29. The article according to claim 24, wherein the polyethylene further has a density of about 0.941 to 0.97 g / cc.
30. 30. The article according to claim 24, wherein the polyethylene is exposed to gamma irradiation at an environmental process temperature of about 25 ° C.
31. 31. The article according to claim 24, wherein the material is sensitive to oxidation.
32. 32. An article, comprising: a material; and a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc, in addition where the material is deposited in the container; wherein the container is exposed to gamma irradiation in at least one selected time from the group consisting of before depositing the material in the container, during depositing the material in the container and after depositing the material in the container, furthermore where the container is exposed to gamma irradiation at an environmental process temperature greater than about 4 ° C.
33. 33. The article according to claim 32, wherein the container is exposed to gamma irradiation at a dose of up to about 100 kGy.
34. 34. The article according to claim 32, wherein the container is exposed to gamma irradiation at a dose of about 15 to 60 kGy.
35. 35. The article according to claim 32, wherein the container is exposed to gamma irradiation at a dose of about 25 to 60 kGy.
36. 36. The article according to claim 32, wherein the polyethylene further has a density of about 0.926 to 0.97 g / cc.
37. 37. The article according to claim 32, wherein the polyethylene further has a density of about 0.941 to 0.97 g / cc.
38. 38. The article according to claim 32, wherein the container is exposed to gamma irradiation at an environmental process temperature of about 25 ° C.
39. 39. The article according to the indication 32, wherein the polyethylene is in contact with the material after depositing the material in the container.
40. 40. The article according to claim 32, wherein the material is sensitive to oxidation.
41. 41. An article, which includes: a medicinal product; and a container, wherein the container comprises polyethylene having a density greater than about 0.925 g / cc, in addition wherein the medicinal product is deposited in the container; wherein the container is exposed to gamma irradiation in at least one time selected from the group consisting of before depositing the medicinal product in the container, during the deposition of the medicinal product in the container and after depositing the medicinal product in the container.
42. 42. The article according to claim 41, wherein the container is exposed to gamma irradiation at an environmental process temperature greater than about 4 ° C.
43. 43. The article according to claim 41, wherein the container is exposed to gamma irradiation at an ambient process temperature of about 25 ° C. - 47
44. 44. The article according to claim 41, wherein the container is exposed to gamma irradiation at a dose of up to about 100 kGy.
45. 45. The article according to claim 41, wherein the container is exposed to gamma irradiation at a dose of about 15 to 60 kGy.
46. 46. The article according to claim 41, wherein the container is exposed to gamma irradiation at a dose of about 25 to 60 kGy.
47. 47. The article according to claim 41, wherein the polyethylene further has a density of about 0.926 to 0.97 g / cc.
48. 48. The article according to claim 41, wherein the polyethylene further has a density of about 0.941 to 0.97 g / cc.
49. 49. The article according to claim 41, wherein the medicinal product is sensitive to oxidation.
50. 50. The article according to claim 41, wherein the medicinal product is an anti-infective agent.
51. 51. The article according to claim 50, wherein the anti-infective agent is an antibiotic.
52. 52. The article according to claim 50, wherein the anti-infective agent is an antibiotic selected from the group consisting of cephalosporins, 1-inosamides, quinolones, oxa-zolidinones, tet-racicines, penicillin and penicillin derivatives.
53. 53. The article according to claim 50, wherein the anti-infective agent is an antibiotic selected from the group consisting of pirlimycin, ceftiofur, lincomycin, neomycin, penicillin G and novobiocin.
54. 54. The article according to claim 41, wherein the polyethylene is in contact with the medicinal product after depositing the medicinal product in the container.