CA2649116A1 - Films having a desiccant material incorporated therein and methods of use and manufacture - Google Patents

Abstract

Film structures, packages, films and methods of making the same are provided wherein the film structures have a desiccant material incorporated into at least one layer of the film structures and further wherein the film structures can comprise a material for making a peelable seal when the film structures are heat sealed to other film structures. The film structures are utilized for a package to hold a product that may be sensitive to the presence of moisture. The product may preferably be pharmaceutical products, nutraceutical products, or devices such as absorbable sutures or medical stents, although any moisture-sensitive product is contemplated by the present invention.

Description

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. . . n..r Att~rney Docket No.: 007034.000$0 , 1.1 -oz~ 2008 FILIVIS HAVING A DESICCANT MATEItIAL INCORPURATED'THEREYN

AND ! ETH4DS C}F USE AND MANUFACTURE
CRC}SS R.EFERENCE TQ RELATED APFLICATIONS

[011 Thrs international application claims priority to U.S. continuation-in-part patent application Serial No. 11I461,680 f led on August 1, 2006, which is a continuation-in~
õ
part of U.S. patent application Serial No. 111401,633 filed on April 11, 2006.
These applications are incorporated herein in their entirety.

FIELD UF THE INVENTIQN

[02J Embodiments of the present invention relate to a film having a desiccant materxal incorporated therein. Nxore specifically, embodiments of the present invention relate to a film structure having a desiccant materxal within a film. layer of the filna structure wherein said film structure is utilized in a package for a product that may be sensitive to the presence of moisture such as a drug coated medical stent or device. In addition, the em,bodiments of the present invention relate to methods of manufactur%ng and methods of using the film having a desiccant material incorporated therein.

[03J lt is generally known to utilize plastic packaging to reduce exposure of products to atmospheric conditions, such as to moisture or oxygen, which may damage the products. For exarnple, packaging for foodstuffs is well known, in that moisture and oxygen may cause the foodstuffs to become spoiled and inedible or otherwise undesirable. In addition, many products in the medical field, for example pharlnaceutical products, nutraceutical products, and devices such as absorbable sutures, drug coated medical stents or other rnedical devices, may also be very sensitive n to atmospheric moisture.

[041 Typlcally, moisture-sensitive products may be encased in thermoplastic material that is relatxvely impernaeable to water molecules. Speczfically, many polymeric materials are utilized as barriers to moisture transmxssion. For example, a film of high density polyethylene (HDPE), or polyvinylidene chloride-methyl acrylate (PVdC-MA) . .

copolymer may be utilized to restrict the movement of water molecules through the film. Oriented polypropylene, metallized oriented polypropylene, ox metallized .
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. Attorney vocket No.: 047034.00080 2 . , polyester would also be= useful as moisture barrier materrial. In addition, metal foil is known to prevent the transmission of oxygen andlor moisture through polymeric packaging having a layer of inetal foil contained therein.

[05] Although these moisture barrier polymers may be useful in restrxcting the rnovement of moisture into a package, some moisture molecules can still make their way into the package to deleteriously affect the product contaxned therein. In addition, even when barrier materials are effective at restricting the transmission of water molecules through a package, cerlain features of the package may sti11 allow for the transmission of water molecules. For example, where a barrier material is incorporated into a central layer of a film structure and the film structure is sealed to another film structure having a barrier material as a central layer, the edges of the package may not be protected by the barrier . , layers. This may allow moisture to make its way into a package along the edges of a heat sealed package.

[061 One solution to maintaining a particularly low or virtually nonexistent level of moisture within a package is to incorporate sachets of desiccant material into the internal space of the package to remove the moisture from the headspace of the package. A sachet may effectively maintain a very low level of moisture in internal spaces of packages, but may have difficulty maintaining the same consistent moisture levels after the package has been opened and a product has been removed. For example, a typical package of moisture-sensitive products may contain a plurality of the products. A sachet of desiccant rnaterial incorporated lnto the package may only guarantee that moisture level of the package is maintained at a constant or minimal moisture level untxl the package is opened and the first product is thereby removed. The remaining products will be instantly exposed to atmospheric moisture when the seal of the .package is broken.
Although the sachet rnay remove some moisture from the headspace of the package after the package is openedd, the reonaining moisture-sensitive products, having already been exposed to moisture, may already be damaged. This may be especially true in bulk packaged materials where sachets are most often used. Desiccant materials are typically incorporated into liddtngs of jars or in sachets of multi-unit packages.

[07J ln addition, sachets of desiccant material may become saturated with atm,ospheric moisture relatively quickly thereby decreasing or eliminating their effectiveness.

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Attorney Iuocicet No.: 007034.ooo8O ' Moisture-sensitive products, therefore, stand a greater chance of being damaged by moisture in this case.

[081 Moreover, the desiccant material contained in the sachets xs typical.ly in powder or granular form and may leak or otherwise spill from the sachets thereby contaminating the product or products contained within the package. For example, if the desiccant rnaterial contacts a food, pharmaceutical or nutraceutical product or medical device, the food, pharmaceutical or nutraceutical product or medical devxce rnay become contaminated with the desiccant material, which may be damaging to the health of an individual that consumes the food product or uses the medical device. In addition, spilled or broken desiccant sachet contents couid create a deieterious effect on the efficacy of fihe medical device, such as a drug eluting stent (DES).

[09J Additionally, although desiccant material is generally known to reduce the moisture content within a package, typical desiccant materials are "physical" desiccant materials, such as molecular sieves, that bind water molecules within pore spaces of a material.
Typically, physical desiccant materrials absorb water at all humidity levels, but will cease to absorb water when interstices of the physical desiccant material are flled.

, Therefore, physical desiccant materials m.ay be ineffective at high humidity levels.

.[10] An additxonal type of desiccant material may be hydrate forrning agents such as salts.
Typical salts that may be utilized as desiccant material are sodium phosphate di-basic, , potassium carbonate, magnesium chloride, calcium chloride, and calcium sulfate, although many others are known as well. Typically, the drying capacity is greatly influenced by the relative humidity within a package. Generally, no water is taken up by the hydrate-forming agent until the relative humidity reaches a value at whxch the first hydrate forms. In the case of calcium chlortde, for example, the first hydrate occurs at less than about two percent relative hum.idity (RH). water is then taken up by the hydrate forming salt until the first hydrate is completely formed by the salt.
No further water is taken up by the salt until the relative laumidity reaches a second level where the second hydrate forms. This process continues through as many hydrates as the agent fozms at which point #he substance begins to dissolve and a saturated solution is formed.
The saturated solution will then continue to take up water. { .

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Eli] Although these saltsmay be effective at removing water molecules from a quantity of gas that may be contained within the headspace of a package, since the salt only btnds the water molecules within the salt, the water molecules may easily escape back into the package. This is known as breathing, and may cause deliquescence (water droplets and liquidization) inside the package. Typically, this can happeri if the salt becomes saturated and if the temperature of the package increases, or if the pressure of the package decreases, which may occur duri.ng shipment or storage of the package.

[12] In addition, salts may not a11ow moisture levels within a package to fall to a level that is necessary to protect the moisture-sensitive product that may be contained within the package. Typically, since salts have different levels of hydration, humidity levels m.ay remain at certain level without decreasing until the level of hydration changes.

[131 However, these salts may be utilized to maintain certain humidity levels within the headspace of a package. For example, certain products may require that a certain level . , of moisture or humidrty be ma.intained wxthin the package headspace.
Headspace humidity control for products can be manipulated by incorporation of the appropriate hydrate forrning agents, [141 The present invention may utilize chemical desiccant technology, which is more preferable because the moisture level within a package may be maintained at an extrenaely low level. Chemical desiccant materials chemically react with water molecules to form a new product, wherein the water molecules are chemically lncorporated into the n.ew product. For example, calcium oxide binds water in the following reaction: CaO+H2Q---~Ga(QH)2 [15] Because the reaction noted above requires very high energy levels to reverse, it is, for all practical purposes, irreversible. Chemical desiccant materials typieally absorb water at all humidity levels, and will eontinue to take up water at high relative humidity levels. These chemical desiccant materials, therefore, may reduce leveis of moisture wxthin the package headspace to 2ero or near zero, which is often desired to maintain niaximum dryness of the product. .

116] Examples of typical packages or products that would benefit frorn desiccant materxal are naedical kits, such as home pregnancy test kits and medical instruments. In addition, other products include electrostatic shielding packaging for electronic parts, such as I-O.e.
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i printer cartridges, circuit boards, televisions, Dvns, printers, modems, personal computers, and telecommunications equipment, etc. Further, other packaging that would benefit from desiccant material is packaging for foods, such as cheese, peanuts, coffee, tea, crackers, spices, flour, bread, etc. ln addition, other products that would , benefit from desiccant material incorporated into the packaging are shoes, boots, fiZm products and cameras, and products that rnay be shipped by sea, such as high value wood like mahogany that would be damaged if exposed to ambient humidity typically found in cargo ships.

[171 A need, therefore, exxsts for polymeric plastic packaging that may be used in packaging to preserve products that may be sensitive to atmospheric moisture. The packaging may comprise films having a desiccant material incorporated directly into the fxlrn. Zn addition, films are needed that effectively control the level of moistUre within packaging without using sachets or desiccant beads that may become ineffective over time, or that may contaminate products contained within the packaging.
Moreover, films, methods of use and manufacture are needed to overc me the additional disadvantages as no.ted above with respect to sachets, beads or physical desiccants.

SUMMARY C1F THE INVENTI+DN

[18J Aspects of the present invention relate to multilayer plastic polyrn.erzc flexible packaging films having a desiccant matelial lncorporated within a layer of the film.
More specifically, aspects of the present Ynvention relate to a polymeric flexible film having a desiccant material incorporated within a layer of the film that is utilized as a package for a product that may be sensitive to the presence of moisture, such as a drug eluting m.edical stent. In addition, aspects of the present invention relate to methods of manufacturing and using the polymeric film having a desiccant material incorporated therein and methods of packaging, storing andlor increasing the shelf life and efficacy of a medical stent contained witlain a package comprised of the pol'naeriric film.

[19] xt is, therefore, an advantage of aspects of the pxesent invention, to provide a polyrneric plastic packaging film having a desiccant material incorporated therein for packages that may contain moisture sensitive products. These products may be, for example, , foodstuffs, medical devices, pharmaceutical andlor nutraceutical products andlor other products that may suffer fxom the deleterious effects of moisture.
Specifically, medical 5I33' . =1 1 -a2-2oO8 õ
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Atlorney Allvcket No.: 007034.00080 . 6 devices that are useful in healthcare may be packaged using a film having a desiccant material contained within a layer of the f lm to maintain the utility of the devices. The desiccant material is utilized to control the rnoisture level within a package made by the film of the present invention.

[201 zn addition, it is an advantage of aspects of the present invention to provide a film having a desiccant material xncorporated therein that would eliminate the need to incorporate into high cost and marginally effective sachets or beads of desiccaant material that can contaminate products contained within packages if the sachets . P
accidentally release the desiccant material into the package. Moreover, sachets or beads are typically hYgher in cost and may be relatively unsightly. Further, they may take up space within a package that could otherwise be used for product. If the desiccant materials within the sachets or beads are ingested, it may become a healfih hazard. By the present inventxon, the desiccant material is incorporated directly into the packagtng f lm in a.rigid solid state in the packaging filna substrate. , [21] Moreover, it is an advantage of aspects of the present invention to provide a film , wherein the desiccant material is xncorporated into the sealant layer of the film and wherein the film is easily extruded. ln addition, many different types of desiccant M= =
rnaterials may be utilized, thereby allowing for particular relative humidity levels within the packages.

[22] Aspects of the present invention can further reduce packaging costs by allowing for the use of thinner and, therefore, less expensive barrier materzals, such as aluminum foil., in sonae embodiments. For example, many flexible foil packages made using films of the present invention can have barrier layers having thicknesses that may be reduced by about 50% or more. Moisture can enter a package through a film structuie where two film structures are heat-sealed together. Aspects of the present invention reduce the , m.oisture absorption into the product by havxng the film absorb moisture entering the package at the end of the seal.

[23] ln addition, it is an advantage of aspects of the present invention to provide a film structure, and a package made fiherefrom, comprising a seaXant film having a desiccant material and a peelable seal material that allows the film structure to be easily peeZed from another film structure when the film stracture is heat sealed to the other film 6.:.., d33' 11 ~022OO8 ! . CA 02649116 2008-10-10 ~ , . oo7lo66 456 ~
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. Auorney VocKet No.: U07o34,000$0 . 7 structure. This allows moisture-sensitive producis to be contained wzthin a package and be protected from moisture while being easily openable. In addition, aspects of certain embodiments of the materials described herein can add the capacity for a moisture sensitive product to survive ETC] (ethylene oxide gas) sterilizatlon. ETO
sterilization can require medical deviees to be exposed for considerable periods of time, (for . example, 24 hours), to vacuurn, high humidity levels (for example approximately 90%
relative humidity), and high temperatures (for example about 1 20 F), which can be contrary fio the normal operating parameters of a desiccant. Aspects of certain embodiments can provide a means to survive these abuse conditions and still maintain surrrivable nnoisture scavenging capability and capacity to protect the medical device, Aspects of certain embodiments can utilize a multilayer desiccant package including a layer of barrier material that creates a time-delayed effect and postpones the activa.tion of the moisture scavenger. Aspects of certain ernbodiments can provide available desiccant in the package layers following the ETO sterilization Gycle. This can allow for moisture scavenging to keep occurring and therefore assist xn extending the shelf life of current medical devices such as drug eluting stents that presently may be damaged by excessive rnoisture left over in the package after ETO sterilization.

[24J Additional features and advantages of the present invention axe described 1n, and will be apparent from, the detailed description of the presently preferred embodiments and from the drawings.

~ ~~ BRYEF DESC1tIPTIi]N ClF THE DRAwIN+GS

[251 FIG. 1 illustrates a cross-section of a film comprising a desiccant material incorporated therein in an embodiment of the present invention.

[261 FIGr. 2 illustrates a cross-sectional view of a film. "structure having a film layer .
. comprising a desiccant material incorporated therein in anothex embodirnent of aspects ofthe present invention.

[27] FIG. 3 xllustrates a perspective vrew of a package made by the film structure in an alternate embodiment of aspects of the present invention.
, [28] FIG. 4 illustrates a cross-sectional view of the package along line IV-IV, in the alternate embodiment of aspects of the present invention.

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DETAYLED DESCRIPTI(]N DF SEVERAL EMBODIMENTS OF THE INVENTI(]N
[29J The present invention relates to fl.lms, f lm structures, film systems, packages and methods of using andlor manufacturing the films, film structures, film systems and packages of the present xnvention. Specifically, the films rnay comprise a desiccant material incorporated into one or more of the f lms as an integrated component. More specifically, the desiccant material may be contained within one or more of the film layers in a film stracture. For example the desiccant may be contained within a heat sealant layer of a film structure. As a furkher example, the desiccant may be contatned .
, . with an interior Iayer of a film structure and not directly next to a pharmaceutical. The . , film structure may be utilized to produce a film system or package for a moisture-sensitive product wherein said film system ar package has a flrst film structure in face-to-face contact with a second film structure and wherein said film structures are heat sealed together around the edges of the fllm system or package while the product is contained therein. Although many types of moisture-sensitive products may be contaxned within the packages made from the films or film structures of the present invention, the packages ] film systems made therefrom are especially useful for packaging medica7 kits, instruments, and drug eluting andlor medical surgical stents.

[301 One such product that could be packaged is a drug eluting stent. A stent is a medical devace typically used to assist with blood flow. in one embodiment, a rnedical stent can be a tube-shaped metal scaffold inserted typically into the cardiovascular system to prevent artery collapse. The stent can be a solution to the issue of artery weakening resulting from angioplasty balloon dxlation procedures.

[311 A problem affecting about 30 /4 of coronary arteries undergoing angioplasty is restenosis, which is. the process of an artery beconaing xeblocked. ln one embodiment of the present invention a bare metal stent is used. Bare rnetal cardiovascular stents can hold open weakened arteries, yet they lack full effectiveness at preventing restenosis.
The presence of a stent also allows the direct introduction of pharm.acologic agent, or drug, at the required site. An appropriate restenosis drug can be coated onto a stent, with the drug often embedded in a polymer layer for time-release capabilities.
This kind of stent is known as a drug eluting stent, and its use has lowered the occurrence of restenosis from approximately 20-30% to below 10%, Two drug eluting stents have been approved by the FDA for sale in the United States since 2003 and 2004, and ,, . . . _ .~.. ..,,., ... ,, 8133 I: I a22OO8 rInt... , , . .. . _...._ ... ,. ... .. ..... ..... , . , . . ,. , , ; .
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extensive research and testing of new drug eluting stents is currently underway. In addition, surgical stents may be used during dental surgery to guide in the placement of mandibular implants, for example. The employment of surgical stents increases the precision of dental implant surgery. ather pharrnaceutical agents also can be coated onto drug eluting stents, such as paclitaxel and sirolimus, or other pharmaceuticals.
Drug eluting stents can be extrernely sensitive to moisture and oxygen.
Excessive moisture may result in the drug elutxng stent prematurely activating the drug coating prior to surgical plaGement in a body, resulting in a decreased amount of drug coating available on the stent at the time of insertion. Aspects of certain embodiments of the materials described herein may provide a solution to thxs problena of degradation of the drug coating on a drug etuting stent due to moisture remaining in the package and during processing before, during and after the ETa sterilization process.

[32] Now referring to the drawings, wherein like numerals refer to like parts, F1G. 1 illustrates -a film 1 of the present invention. The film 1 may be made from a polymeric material, such as a poiyolef nic material. Preferably, the film may comprise polyethylene selected from the group consisting of ultra low density polyethylene, low density polyethylene, linear low density polyethylene, medium density polyethylene, and high density polyethylene, and may be made via any known method of making polyethylene, such as via Ziegler-Natta catalysts, or single-site catalysts;
such as metallocene catalysts. Moreover, the film may preferably comprise ethylene copolymers, such as ethyXene aipha-olefin copolymers, ethylene-methyl acrylate copolymer, ethylene vinyl acetate copolymer, and other like polymers. xn addition, the film may.comprise polypropylene hornopolymer or copolymer, either al'one or blended with polyethylene or polyethylene copolymers, as noted above. In addition, the ffilm may comprise modified polymeric materials, such as modified via malei~
anhydride, or other like modifiers for polymeric materials having particular characteristics. Specifc materials that rnay be useful as the , sealant iayer include DuPont APPEEL~
and BYNEL or polybutene for peelseal, [33} The film 1 may further comprise a desiccant material 1 o blended therein, such as any , known desiccant material that may blend with polymeric xesins that can be made into hlms. Specifically, desiccant materials that may be useful for the present invention include, but are not limited to calcium oxide, magnesxum oxide, strontium oxide, 9/33 1 1~a2-2oo8 , ;,...,-.., ....... ......... . .,.,., ,, ' .. .. . . .,.,.. . ,.. .
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, , Attorney vocKet o.: 007034.00080 _ aluminum oxide, partially hydrated aluminum oxide, sodium phosphate di4basic, potasslunl carbonate, magnesium chloride, calcium sulfate, molecular sieves, ctays, or , r any other desiccant matertal useful for the present inventaon. Xn some embodiments of the invention chemical desiccant materials are preferred, such as calciuzn oxide, magnesium oxide and strontium oxide.
, [341 Chemical desiccant materials are preferred in some embodiments because chemlcal desiccant materials irreversibly bind water molecules within the crystalline product via a chemical reaction. The water molecules typically cannot be released into the package at higher temperatures or lower pressures. In additton, chemical desiccant materials may more effectively remove humidity from the headspace of a package made from the film 1.

1351 Hydrate-forming salts may also be used, and may effectively mainta7n constant relative humidity levels wxthin the headspace of a package made from the h.lm 1.
Specific levels of humidity may be maintained depending on the hydration levels or state of the hydrate forrning salt within the polymer materi.al, [361 A preferred chernical desiccant material that is useful for the present invention is calcium oxide, which irreversibly forms calcium hydroxide via a chemical reaction.

[37] The desiccant' material can be incorporated into the film 1 , in an ernbodiment, at a level of between about one weight percent and abouf 90 weight percent. In an embodiment, the desiccant material can be incorporated into the film 1 at a level of between about 20 . , weight percent and about 60 weight percent. In another ernbodiment, the desiccant material can be incorporated into the filna I at a level of between approximately 10 weight percent and approxim.ately 40 weight percent. In yet another embodiment, the desiccant material can be incorporated into the film I at a level. of between approxirnately 20 weight percent and approximately 40 weight percent. In an additionaX
embodiment, the desiccant material can be incorporated into the film I at a level of approximately 30 weight percent.

1381 ln an embodiment, the film 1 may comprise a quantity of a masterbatch of polyrner and desiccant material. For example, the masterbatch may preferably cornprise polyethylene having calcium oxide blended therein. Specifically, the masterbatch may comprise about 50 percent by weight polyethylene and about 50 percent by weight calcium oxide, 1 4133 1 1 -02-2Oo8 .
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The masterbatch can be further blended into anothher polymeric material, such as low density polyethylene, in a ratio of about 60 percent by weight masterbatch and percent by wexght low density polyethylene. Therefore, the film 1, in an embodiment, may have a desiccant material content of about 30 weight percent in the film 1, In additxonal embodiments, the masterbatch can be blended with a modified ethylene vinyl acetate copolymer or modified ethylene methyl acrylate copolymer, such as DuPont APPEEL or polybutene resins, which can provide the sealant filna structures with a peelable seal feature, [391 lt shauld be noted that although the film 1 is illustrated as a single independent layer, film 1 rnay be incorporated into a multilayer structure, such as via coextrusion with other film layers, extrusion or coextrnsion coating, adhesive lamination, extrusion lamination or any other method of making multilayer film structures. Zn addition, the other films and layers mentioned herexn may be single independent layers, or may be incorporated into a naultilayer structure such as vxa coextrusion with other film layers, extrusion or , coextrusion coating, adhesive lamination, extrusion lamination or any other method of making multilayer f lm structures. For purposes af packaging drug eluting stents a coextrnsion is preferred, as a coextrusion can allow for the addition of a barrier layer to protect the desiccant in the moisture scavenging layer. The incorporation of a barrier layex may also be achieved by aclding an adhesive or extrusion coating layer to an xndependent layer. An aspect of the current invention can involve the use of moisture scavenger desiccant in combination with a barrier layer to allow the moisture scavenger desiccant layer to survive the ETO sterilization cycle with remaining efficacy to protect th,e drug eluting stent from being exposed to excessive moisture. This protection from moisture can allow the drug eluting stent to have a greater shelf life and vatue to the users. . S
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[40] FIG, 2 illustrates an embodiment of the invention, in which a f lm structure 100 of the present invention incorporates a fxlm layer 114 having a desiccant material incorporated therein, as detailed above with relation to lhe film 1. Specifically, the film layer 11 Q
may comprise a polyolefintc material, such as polyethylene, as described above, or polypropylene. Preferably, the polyolefinic material comprises polyethylene.
The desiccant material may comprise a chemical, physical, or hydrate-forming desiccant material, although a chemical desiccant naaterial is preferred.

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xnorney uocKet No.; 007034.00080 [41] In addition, the f lm layer 110 may be between about l mil and about I O
mils thick and may form a sealant layer or a product contacting layer in a package made from the film structure 1 00.1n an embodiment, the film layer 110 rnay be between about I
mil and 5 mils thick. In another embodiment, the film layer 110 can be between about I.5 mils and about 3.5 mils thick.

[42] The film layer 110 may further comprise a component that provides a peelable seal when used as a seaiant layer that is heat sealed to another film structure or to xtself. A
resin blend that ailows for a peelable seal is DuPont APPEEL , which is either modified ethylene vinyl acetate copolymer or modified ethylene methyl acrylate copolymer, each of which is designed tQ provide a peelable seal when heat-sealed to other fiam layers, such as polyvinylchloride (PVC). Alternatively, a seal-poisoning component may be utilized, wheretn a material, such as polybutylene, may be blended with the sealant resins to provide "poisoned seals" when sealant layers made from such reSins are heat-sealed to other film layers, which can provide adequate sealing protection but can be easily separable using digital pull-apart forces. This is one preferred method drug eluting stent packaging. In addition, a desiccant material, such as calcium oxide (CaO) can be used as the peelable seal cornponent, such that when heat-sealed to another film component, the film structure may be relatively easily separable using digital pull-apart forces.

[43] Alternatively, the peelable seal component may not be present in the heat sealant layer, as described above, but rnay be present in a heat sealable layer of a second fxlm a structure that is heat-.sealed to the film structure containing the aesiccant materiaL This allows the peelable film component to be present in either the film structure containing the desiccant material or the second film structure that the film structure containing the desiccant material is heat-sealed to. In additxon, the peelable seal cornponent of the present invention may be contained within the first tie layer or adheslve layer of the film strueture containing the desiccant material, or alternatively, to a tie layer or adhesive layer of the second film structure that the film structure containing the desiccant material is heat-sealed to. Therefore, it should be noted that the peelable film component can be contained within any layer or any film structure that allows the film structure containing the desiccant material to be pulled from the second film structure I . , .., , , .d ._ ....
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with digital pull-apart forces, while maintaining protection from moisture prior to pulling the film structures apart.

1441 In an embodiment, the rernaining film layers of a film structure of the present invention may be any material that may be utilized to forrn a package with the film layer 110 as a' sealant layer or a product contacting layer. Moreover, any nurnber of layers may be incorporated into the film structure 140 as may be needed to form a package having desired characteristics. An embodiment of the film structure of the present invention zncludes the heat sealant layer 110 as noted above. The heat seal ant 1 ayer 11 Q may be adhered to a barrier layer 114 by a tie or adhesive layer 11 2. In addition, the filrn structure may comprise an outer layer adhered to said barrzer layer via a secon tie or . adhesive layer disposed between said outer layer and said barrier layer.
Finally, the film structure of the present invention may comprise a primer layer or printed layer disposed between said outer layer and said tie adhesive layer.
j -[45] In an embodiment, a tie or adhesive layer may be a coextrusion of low density polyethylene (LDPE), and ethylene acrylic acid copolymer (EAA), wherein said LDPE
is disposed adjaGent to the sealant layer and the EAA is disposed adjacent to the barrier layer, as descrribed below, although other polymeric materials may be utilized that adhere the heat sealant layer to the barrier layer. In an embodiment, the tie or adhesive layer is a non-aqueous adhesive. In some embodinaents of the invention, use of a non-aqueous adhesive may assist with diminishing the amount of water or moisture in the.
headspace within a package.. The barrier layer may be made of a polyvinylidene .
chloride-methyl acrylate copolymer, Honeywell ACLAR (a high density fluorocarbon polymer), metal foil, such as aluminum foil, cyclo-olefin copolymer. (COC), a blend of c C and high density polyethylene, nylon, high density polyethylene, polypropylene, a such as oriented polypropylene and metalli2ed oriented polypropylene, metallized polyester, or blends of . these materials. In an embodiment, the barrier layer rnay be approximately 70 - 90% by weight COG and approximately I O- 30% by weight HDPE.
In another embodiment, the barri.er layer may be approximately SQ% by weight CaC
and approximately 20% by weight HDPE. Other percentages for blends of COC and +HDPE also naay be used. The barrzer layer may be any thickness that may be necessary to reduce the transxnission of water molecules through the film structure I00.
In an embodiment, the barrier layer may be about 0.35 mils when the barrier layer is .
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, aluminum foil. xn other embodiments, the barrier layer may have a thickness of approximately 75 microns or less, and may have a thickness of approximately 50 microns or less. In another embodiment, the barrier layer may have a thickness greater than 75 microns, including a thickness of l00 microns or more. Uf course, the barri,er layer rnay be other thicknesses depending on the barrier rnaterial that is utilized. The tie or adhesive layer may aid in binding the polyolefinic material of the heat sealant layer to metal foil that may be used as the barrier layer.

[461 Tie or adhesive layer 116 may be a coextrusion of LDPE and BAA and may be similar, if not identical, to film layer 112, wherein the EAA is disposed adjacent to the bamer layer 114, and the LDPE xs disposed ad] acent to the film layer 118 or film layer 1Z0, as described below. Film 1 ayer 11 smay be a primer layer andlor a printed layer.
lf the filrn . .
layer 11 8 is a printed itik or pigment layer, it may form a printed label or other printed indicia on the f lm structure 100. Finally, f lm layer 120 may be an outer abuse layer, and may comprise Honeywell ACLAR , polyethylene terephthalate (PET), oriented palypropylene (OPP), polyethylene, nylon, foil, metallized substrates, or any other material apparent to one having ordinary skill in the art. Optionally, a secondary sealant layer (not shown) m ay be disposed adjacent to the sealant layer 110 and may protect the product from the desiccant material contained in the sealant layer 110. The optional secondary sealant layer may form the product contacting layer of the f lm structure 100 and may be about 0.5 mils or less. Hvwever, the secondary sealant layer may be any polymeric material that helps to protect the product from contacttng the desiccant material.

[47] As stated above, the barrier layer 114 may be a nrletal foil or Honeywell ACLAR that may be any thickness (for example only, 25 microns, 50 niicrons, 1 00 microns) to reduce the transmission of moisture through the film. The number of pinholes present in a metal foil, for example, is inversely related to the foil thickness.
Therefore, a thicker foil tends to have fewer pinholes. However, if the desiccant material of the present , invention is in the heat sealant layer 110 thinner foil or ACLAR can be utilized in packages made from the film structure 100.

1481 Nietal foil or ACLAR can be utilized to provide an effective barrier against moisture transmission through a film structure. However, metal foil can be relatively expensxve and difftcult to p'rQcess. Therefore, the desiccant sealant layer 110 is effective at I 41 33? r , .-.
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in addition to the inherent barrier protection provided by metal foil. Barrier layers may be relatively thinner when a film structure incorporates a desiccant sealant layer into the f lm structure, thereby saving on cost. Moreover, bamier layers such as COC l HDPE
blends may be used more often when desiccant hlms are used.

1491 FIG. 3 illustrates a package 200 made from a film structure of an ernbodiment of the present invention. Specifically, the package 204 is made from the film structure 100, as illustrated with respect to FIG. Z, described above. Specifically, the package 200 may comprise tw filxn structures that are heat sealed together via a heat seal 202 that is formed around a perimeter of ,the package 200, Alternatively, the package 200 may cornprise a single film structure that is folded and heat sealed around the perimeter of the package 200. The package 200 may further comprise a space 204 to contain a product 206. The product 206 may be sensitive to moisture, so that a desiccant naaterial contained within the film structure or film structures reduces or eliminates the amount of water molecules witihin the space 204. A preferable product contained within the package 200 may be a kit useful in the medical field. A single instrument may be contained within the package 2`00 so that when opened and the instrunnent xs removed, there are no other instruments wxthin the package 200 to be contaminated by moisture.

[50] FIG. 4 illustrates a cross-section of the package 200 along line IV-IV, in an embodiment of the present invention. The cross-section shows two film structures 2 10, 2 12 that are heat sealed together at heat seals 202. The two film structures may be identical, and may comprise the same film layers as described above with respect to film structure 100. Specifically, the two film structure 210, 212 may cornprise a plurality of layers: a sealant layer 110 of a polyolefinic material and a desiccant material; a tie or adhesive layer 11 2, comprising, for example, a blend of low density polyethylene and ethylene acrylic acxd copolymer; a barrier layer 1 I4 comprising, for exarnple, a foil, ACLAR .
or metallized material; a tie or adhesive layer 11 6 cornprising, for example, a blend of low density polyethylene and ethylene acrylic acid copolyrner; a priiated or primer layer 11 8; and an outer or abuse layer 120 comprising, for example, PET. The product 206, such as a medical instrument, is contained within the package 200 in the space 204.

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[51] while foil can reduce or effectively eliminate water transmission through film structures 210, 212 of the package 200, it cannot completely eliminate the transmission of moisture through the edges of the film structure. For example, FIG. 4 illustrates the cross-section of the package 200 along line IV4V. As shown, the rnetal foil layer 114 of , each film structure 21 o and 212 are displaced from the portions of the film structure 210 and 212 that are heat sealed together. Therefore, there is an area 214 that is not . protected by the metal foil layer 114 that may transmit water moXecules into the space 204. If the desiccant material is incorporated into the heat sealant layer 110, then the desxccant material may effectively block moisture from passing into õthe interior space 204 of #he package 200 thereby protecting the moisture-sensitive product contained therein. In addition, if the desiccant material is in the heat sealant layer that contacts a moisture-sensitive product or other contacts the interior space 204, the desiccant material can remove moisture molecules that rnay be contained within the interior space 204. The desiccant material also can remove moisture molecules when it is in a layer further away from the moisture-sensitive product. , .

[52J In an additional ernbodtment, several films andlor layers may be used in combination to forrn multiple film structures of a film system. One film layer that can be incorporated into a film structure is a layer contalning a desiccant. The desiccant layer can include a chemical desiccant that can act as a moisture scavenger. Examples of chemical desiccants include calcium oxide, magnesium oxide, strontium, oxide, aluminum oxide or other chemical desiccants. The chemical desiccant can be combined with a polymeric material to form a film. Polymeric materials that can be used include polyethylene, linear low density polyethylene, CQC and other polymeric mater2als. In an embodiment, the desiccant falm layer can include approximatety 20 -, 40% by weight . , , desiccant and approximately GO - So% by weight polymer. In another embodiment, the desiccant layer can include approximately 10 - 40% by weight desiccant and approximately GO - 94% by weight polymer. In another embodiment, the desiccant layer can include approximately I o- 50% by weight desiccant and approximately 90% by weight polymer. Depending on the desired capacity of the f lm system to scavenge rnoisture, more or less desiccant can be incorporated infio the desiccant layer as well as the other layers of the film structures. In one embodiment, a desiccant f lm layer can have a thxckness of approximately 4 w- 8 mils. In some embodiments, a , t :...., .. v^ :. .... ..... ... .. ...:..'. . ',:: .:Y
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desiccant fiim layer can have a thzdkness of approxirnately 5- 7 mils or approximately . 6m.ils. ' [53J In other embodiments, molecular sieve desiccants can be incorporated into a desiccant film layer. In one embodiment, the molecular sieve desiccant is a crystalline alumino-silicate. In some embodiments, the molecular sxeve desiccannt can have a pore size of no more than approximately 3, 4 or 5 angstroms. Molecular sieve desiccants may act more rapidly than many chemical desiccants. Thus, molecular sieve desiccants may take up water or moisture in a relatively quick manner. Molecular sieve desiccants may then reach their capacity to hold water. Many chemical desiccants, on the other hand, have a larger capacity to hold moisture or water than rnolecular sieve desiccants.
Many chemical desiccants work more slowly at absorbing water or moisture than molecular sieve desiccants. However, many chernical desxccants will continue to absorb water longer than and will absorb rnore moisture than molecular sieve desiccants.

[54] The film structure also may include a product contact layer. The product contact layer may be comprised of a substance that has been deemed acceptable to be in contact with a product such as a pharrnaceutical. Ine one embodiment, the product contact layer can xnclude polyvinylchloride (PVC). In another embodiment, the product contact layer can include COC, HDPE or a blend of CDC and HDPE. Blends of CaC and HDPE in ' some embodxrnents can be approximately 70 - 90% COC and approximately 10 --30%
HDPE or approximately S0 /4 COC and approximately 20% HDPE. The product contact layer can have a thickness of approximately 62 microns or less in one embodiment, approximately 50 microns or less in another embodiment and approximately 100 microns, 200 microns or more in other embodiments. .

[551 The f lm structure also can include a barrier layer. The barrier layer can serve to limit the amount of moisture that can pass through the film structure. In some embodiments, the barrier layer can znclude one or more of the following substances:
polyvinylidene . chloridemthyl acrylate copolymer, high density fluorocarbon polymer, cyclo-olefin copolymer, ametal foil, nylon, high density polyethylene, oriented or cast polypropylene, metallized oriented polypropylene, andlor metallized polyester. In one embodiment, the + thick.ness of the barrier layer is approximately 75 microns or less. In anothher embodiment the barrier layer has a thickness of approximately 62 microns or less. In an additional embodinaent, the barrier layer has a thickness of approximately 50 microns or ... . .. ,, . . ,...
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less. In another embodiment, the barrier layer has a thickness of approximately 25 microns or less. In an additional embodiment, the barrrier layer can have a thickness of less than 10 rnicrons, especially where foil is used as the barrier. In a further embodiment, the barrier layer can have a thxckness of approximately 100 or 200 microns or more. The thickness of the barrier layers will depend on the purposes and . design of the overall film system. .

. [56] A frst film structure can be created by combining a barrier layer, a desiccant layer and . a product contact layer. These layers can be combined through the use of an adhesive.
The layers alsa can be coextruded or combined in other methOds known in the art. In one embodiment, the adhesive may be a non=aqueous adhesive. The adhesive can be ethylene acrylic acid copolymer in one embodiment.

. [57] In one embodiment, sevcral film layers are lamxnated together. An adhesive can be applied on one side of a desiccant :dlm layer. The adhesive and desiccant layer can then be put through a drying tunnel to evaporate all or the majority of the solvent contained in the adhesive. After the drying tunnel, the desxccant layer containing the adhesive can be adhered to a product contact layer that may include a polymeric material such as PVC. The adhesive in some circumstances can be referred to as an adhesive layer.
, [581 ln an ernbodiment, the film structure containing the desiccant layer and the product contact layer can have an adhesive disposed on the side of the desiccant layer opposite the product contact layer. Like the adhesive mentioned above, this adhesive can be a non-aqueous adhesive. The film structure can then be passed through a drying tunnel.
The side of the desiccant layer having the adhesive can then be placed in contact with , and adhered to a barrier layer. The three layers described above, the product contact layer, the desiccanti layer and the barrier layer, can form a f lm structure.
In one embodiment, the process of combining the product contact layer, the desiccant layer and the barrier layer takes place as a continuous process.

[591 In another aspect of the invention, two desiceants can be used in the same film structure, ln one embodiment, a' molecular sieve desiccant and a chemical desiccant can be used in conjunction with each other. In one embodiment, a molecular sieve, desiccant film can be formed and a chemical desiccant film can be formed. The chemical desiccant film can contain both a chemical desiccant and a polymeric material.
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.. attorney uocxet No.: 007034.00080 The molecular sieve desiccant film can contain both a m,olecular sieve desiccant and a polymeric material4 The polymeric material for both desiccant films can be polyethylene or linear low density polyethylene or other suitable polymer.
These two desiccant films can be joined together into a film structure through adhesion, coextrusion, lamination, heat sealing or other methods. Adhesion can be obtained through the use of a non-aqueous adhesive.

[60] A film structure containxng both the chenaical desiccant film and the molecular sieve desiccant film can be used in manners similar to those described herein for a single desiccant film layer. The dual desiccant film structure can be used in place of a single desicca.nt film layer or can be used in addition to a single desiccant layer.
The terms film struGture, f lm and multilayer rilm are frequently used interchangeably arid should be considered interchangeable where appropriate herein.

[61] In another aspect of the invention, a single film can incorporate several different types of desiccant. In one embodiment, a film can incorporate a chernical desiccant and a . molecular sieve desxccant. In an embodiment, the film can include approxxmately 5-354/o by weight chemical desiccant, approximately 5 - 35% by weight molecular sieve desiccant and approximately 30 - 90% by weight polymeric materials such as polyethylene, linear low density polyethylene, CUC or other polymeric materials , [62] In one aspect of the invention, it may be desired to store one or more layers or film structures that include a desiccant for later processing. In some cases, a desiccant f lm naay be sent from one processing location to another location for the addition of a product contact layer and a barrier layer. In some cases, a filrn structure such as a strucxure including a desiccant layer, a barrier layer and a product contact layer may be shipped to a remote location for further processing. A film layer or f lm structure containing a desiccant can be wrapped in a barrier layer such as a foil or other barrier layer and stored. The wrapping with the barrier layer can place the barrier completely around the desiccant containing film or film structure, thereby greatly inhibiting the passage of water or moisture into the desiccant. In an ernbodiment, the film layer or flm structure can be stored for up to b months without significant loss in the moisture scavenging capacity of the desiccant. Zn other embodiments, the f Irn layer or film structure can be stored for up to I Z months, I8 months or more.

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[631 The film structures 1 04 may be made via cast coextrusion, extrusion coating and/or extrusion lamination, adhesive lamination, blown-film coextrusion or monolayer extrusion or any other film-making method generally known to those having ordinary skill in the art. In an ennbodiment, extrusion temperatures for blown films and cast films can be approxirnately 300 - 550 Fahrenheit. In an enabodiment, the desiccant heat sealant layer may be made by compounding the desiccant material into the polymeric resin, and extruding or coextruding via blown extrusion, cast extrusion, or extrusion lamination into a monolayer film or a muitilayer film. The remainder of the film structures may be extrusion or adhesive laminated together with the monolayer film or multilayer film. The desiccant heat sealant layer can be larninated to the remainder of the f lm structure, including the barrier layer of the film structure.

[64] As noted in the above a paragraph, several methods exist for constructing an effective flexible or rigid package using the present invention. These methods include, but are not limited to:

[65] 1. Blown film monolayer extrusion or multilayer coextrusion of a desiccant f lm that is extrusion laminated to a barrier matertal. This method can be preferred in certain . ernbodiments. .

[661 2. Blown film monolayer extrusion or multilayer coextrusion of a desiccant film that is adhesive laminated to a barrier material with the use of adhesives and/or prrirners . to bond the desiccant film to the barrier layer.

[671 3. Cast f lm monolayer extrusion or multilayer coextrusiOn of a desiccant film that is extrusibn laminated to a barrier layer.

[68] 4. Cast film monolayer extrusion or multilayer coextrusion of a desiccant flm that is adhesive larninated to barrier materials with the use of adhesives and/or primers to bond the desiccant film to the barrier layer.

[691 5, Extrusion or coextrusion coating wherein the desiccant layer and/or an adhesive layer are ex,trusion or coextrusion coated directly onto the barrier layer.

[701 af course, any other methods of making films, film structures, f lm systenas and a packages of the present invention may be utilized as may be apparent to one having ordiriary skill in the art. Moreover, although f lm structures having barri.er materials .... .. . .,.. , .. . . , , 20133 - =1 . I ~ .. ., ~D22oQ8 I

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1711 Zn addition, in an alternate embodiment of the present invention, the desiccant material may further be utilized to provide an indicator showing whether the desiccant material has reached its capacity. In addition, this naay further provide an indication whether fhe package integrity has been compromised. Generally, desiccant materials become cloudy when they have absorbed water, especially when incorporated into films that are transparent. In addition, when the desiccant material absorbs moisture, the package becomes heavier, less transparent and more opaque. An image or a message may be provided in a film structure confiaining the desiccant material. when the image or .
message is obscured to a certain point; such as when the image or message cannot be viewed anymore because of the cloudiness of the package, an individual may know that the desiccant materiai has reached its capacxty, or is close to reaching its capacity, thereby indicating that the package, and therefore the product, is relatively old, or the package has been compromised and moisture has entered the package.
Alternatively, the package may contain a moisture indicator visible through at least a portion of the package, such as a window or the like, to form or change colors, thereby indicating the , presen.ce of excess moisture. Iri an embodiment, cobalt chloride can be used as a moisture indicator. ' [72J Zn addition, several desiccant film layers can be used in a single film structure. In one , embodiment, a molecular sieve desiccant filrn layer and a chemical desiccant fihn layer may be used in a single film structure along with other layers such as a product contact layer, a barrier layer and adhesives.

[73J An aspect of the invention involves use and processing of film products in environments with humidity. Certain current packaging operations, such as packaging for pharmaceutical and/or nutraceutical products, can take place in clean rooms under low humidity conditions. Yn some cases humidity during some current packaging processmay be kept at levels of approximately 20% relative humidity (RH) or lower.
, Aspects of the 'current invention allow for packaging operations to take place in higher humidity environments.

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[74] In one embodiment of the invention, a film structure comprising a product contact layer, =
a desiccant layer and a barrier layer can be adhered to a seGond flm structure comprising a product contact layer, a desiccant layer and a barrier layer. The f lrrx structures can be adhered through heat sealing, adhesives or other method of adhesion.
After this adhesion step, the f nished film system can be referred to as a package and a product, such as drug eluting stent, can be placed in the package. Each step of the process of forming the f Im structures into a package, including the addition of the -products, can take place at ambient humidity. In an embodiment, the various steps detailed above can be carried out in an environment having an RH of greater than approximately 50%. In another embodiment, the various steps can be carried out in an environment having an RH greater than approximately 70%. In a further embodiment, the vari,ous steps can be carried out'in an environment having an RH that is greater than I
approximately 80 /a.

[75J Due to the desiccant in the hlm, the relative huxnidity in the package interior cavity will rapidly decrease from tihe relative hurnidity of the packaging environxnent.
In an embodiment, the relative humidity in the cavity rnay be more than approximafely 50%
immediately or shortly after the packing process is complete. Due to the desiccant in the flm, the relative humidity in the cavity may decrease to less than approximately 20% after approximately 36 hours after the packaging process is complete. Yn another aspect of the invention, the relative humidity may decrease to a relative humidity pf less than approximately 14% 36 hours after the packaging process is complete. In further ernbodiments, the decrease in relative humidity will occur where the initial relative humidity of the cavity is higher than approxirnately 50%. In an embodiment, the initial . relative humidity of the cavity may be more than approximately 70%, more than approximately 80% or rnore than approximately 90%, and the relative hurnidity of the cavity in an embodiment will be less than approximately 20% 36 hours later and in another embodiment will be less than approx,irnately lo% 36 hours later. 'rhe relative humidity in the cavity.will remain at a level of less than approximately 20%
(in one embodiment) or less than approximately 10% (in another enabodiment) for a perxod of more than 6 months (in an embodiment) and for a period of more than l2 months (in an ernbo iment), 22133 ` 11-02-2 . Q03 . .
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[761 By keeping the relative humidity of the headspace in the cavity low, the shelf life of the drug eluting stent, medical device, pharmaceutical or nutraceutical products can be increased. The shelf life of a pharmaceutical or nutraceutica} product in a package containing a desiccant film described above will be more than approxirnately 1 year (in one embodiment), more than approximately 2 years (in another embodiment) or more than approximately 4 years (in another embodiment) as long as the integrity of the package is not compromised. The current shelf life of sorne drug eluting stents can be limited to about 60-90 days, which is an economic burden that results in a high cost , factor associated with drug eluting stents. An aspect of the invention, wherein a drug eluting stent is stored in a deszccant package as described herein, provides an increased shelf life of more than about b months in an embodiment. In other embodiments the shelf life of a drug eluting stent in desiccant packaging nnay be more #han 1 year. Zn an additional embodiment, the shelf lxfe is greater than 2 years.

[771 A.s with all materials to be used during surgery, stents must be sterilized. The most common sterilization method for stents is ethylene oxide (ETO) gas sterilization, because xt can be gentle to the material being sterilized, yet kil1s microbial agents. In an embodiment, ETO sterilization involves exposure to a concentration of ETC3 of approximately 5oo-1Q4 mglL in an atmosphere of approximately 90% (in one , embodirnent) relative humidity or at least 50% relatlve humidity (in another embodiment) or 30% humidity in an additional embodiment at a temperature of at least approximately 110 F in one embodiment, at least approximately 115 F in another enabodiment and approximately 125 F xn a further embodi:rnent. The exposure can take place for up to an hour in one enlbodirnent, and up to ten, szxteen, or twenty-four hours in other ernbodiments. The exact conditxons are variable. ln an aspect of the invention, , sterilization efforts of stents may be canducted at an ETO
concentration'between about 200 and 500 mglL in an atmosphere of greater than 50% relative humidity and a , temperature of about 125 F for at least twelve hours. In another embodiment, sterilization of stents may be performed using at least 1400 mgJL ETO an an atmosphere of',greater than 90% relative humidity at a temperature at or above approximately 1 l 5 F
for at least approxirnately one hour. The antimicrobial effectiveness of ET4 increases , . , proportionately with increased temperature, and sterilizatxon time decreases as ETO
concentration is raised.

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Once the package is removed from the sterilization chamber, it can be sealed (such as through ~
heat sealing) and any Tyvek vacuum vent cut off.

[79J A disadvantage of ETO sterilization is that it introduces humidity to a moisture-sensitive product. The current shelf life of a sterilized drug eluting stent can be about two to three months, maxnly due to degradation of the drug by moisture inside the package. There are two sources of this rnoisture, the first being the ETO
steriiization atmosphere and the second being ambient moisture diffusing through the sealed stent packaging. To extend the drug eluting stent shelf life, these sources of moisture can be addressed. .

[801 In one aspect of the invention a package is used for storage of a moisture~sensitive product following sterillzation via ETO gas of the moisture-sensitive product within the ;
package: The package, in an embodiment, can be szmilar to the packages described w..

herein. The package can be similar to the package shown in figures 3 and 4 in an embodiment. The package can comprise a multilayer film comprising a first polymeric product contact layer, a f rst desiccant layer, a second desiccant layer, a first barrier layer, and a fxrst laminating layer. The thickness of the polymeric product contact layer can depend on the permeation rate of the particular polymer employed.
According to the multilayer films herein, the desi ccant layers may each comprise a desiccant, such as calcium oxide or molecular sieves, blended with an extrudable olehn.
Advantageously, in one embodiment, minimal or no misture will diffuse through the product contact layer to the f rst desiccant layer during the time of the sterilization process, where it would consume the desiccant. 4n the other hand, in an embodinaent, the moisture will be able to diffuse through the product contact layer following sterilization to prornptly lower the relative humidity of the tnterior of the package and protect the product from degradation while it is in storage. [81J In one aspect of the invention, the second desiccant layer zs located between the frst desiccant layer and the barrzer, for instance foil, layer. The second desiccant layer can , ,,.. .. , 24133 1 1 ~o2-2oo8 CA 02649116 2008-10-10 d . , .., . ., , _ rinted: 2&-000$ DES-~PAI~D PCTI .. . .,. . . _ '~~~ US 20071066 456~
..
. :. . _ . _ _ . "Attorn~y VocKet No.: 007034.00080 absorb moisture that enters from the outsade of the multilayer film package.
It also can act as a backup desiccant in the event that the first desiccant layer becomes saturated.
Th`e f rst desiccant layer and the second desiccant layer may or may not comprise the same desiccant material. In one aspect of the invention, lhe first and second desiccant layers include chemical desiccants. In another aspect of the invention, one of the desiccant layers includes a molecular sieve desiccant and the other includes a chemical desiccant, [82] Another ernbodiment of the invention is a medical system including a moisture sensitive drug eluting stent and a desiccant package comprising two multilayer films, each of which include a first polymeric product contact layer, a first desiccant layer, a second desrccant layer, a first barrier Iayer, and a first laminating layer. The f lms are joined together through heat sealing or other process to form a packa.ge. In aspects of the invention, the desiccant package includes a plurality of desiccant layers, barrier layers, andlor lamtnating layers. Combining the ability to include any number of the various types of layers wxth awxde choice of layer thicknesses, the package is tailorable to different applications. In an embodiment of the invention, the desiccant package may be formed by folding one multilayer film into a type of pouch and sealing the edges.
This provides a single space to contain the drug eluting stent, for exarnple as illustrated in Figs. 3-4, wherein element 204 refers to the space and product 206 refers to the stent.

[831 An additional aspect of the invention is a method to sterilize a drug eluting stent by the ETO gas method. A drug eluting stent may be in a multilayer desiccant film package comprzsing a folded and sealed multilayer f lm including a product contaGt layer, two desiccant layers comprising desiccant materials that may or may not be the same, a barrier layer, and a lamrnating layer. In an embodiment, the package comprises two multilayer films as described herein. These two hilms, in an embodiment, can be heat .
sealed to each other near or at their perimeter. The desiccant f lm package may be . 1 sealed through a Tyvek vacuum vent that allows the ET4 gas to enter and exit the package. As described above, ETO sterilization of drug eluting stents involves the ~rariables of ETO concentration, relative humidity, temperature, and exposure time.
Each variable 1s operational over a range Qf chosen values, leading to a plurai ity of .
potentxally effective conditions for sterilizatxon. At the conclusion of the steriZization, 2513 . . :,:,, ., ..,.

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the ET4 gas is pumped out of the sterilization chamber. Once the package is removed from the sterilization chamber, it is sealed and the Tyvek vacuum vent cut off:
Regardless of the amount of hurnidity remaining in the sealed package at the completion of the sterilization process, the relative humidity in the package space at 36 hours after sterilization will be below approximately 24% in an embodiment.
Froviding that the desiccant package remains sealed, in aspects of the invention the relative humidity in the package space will be maintained below about 24 'o after at least 6 days, 6 months, I year, or 2 years in different embodiments.

, EXAMPEES

[841 The following examples are illustrative of preferred embodiments of the present invention, as described above, and are not meant to lixnit the invention in any way. .

. Example 1 [851 The following Table I illustrates preferred materials and gauges for the film structure 100, as described above and illustrated with respect to FIG. 2. .

Material Gau~e PET , 0.48 mils INI~ 0.1 #lream LDPEIEAA Coextrusion 0.5 mils FoII 0.3 5 n111s LDFEIEAA blend 0.5 mils LDFEICaO blend 1.5 mils , Example 2 . .
[86] The following Table 2 illustrates preferred materials and gauges for the film structure I oO, as described above and illustrated with respect to FIC. 2, in an alternate .
embodiment of the present invention .
. TABLE 2 , Ma~erial ~au e - . . j 26133 s OO8 .
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.,.. . , _ . ,_ .. .
rIn: . ,.. .: . ..... . .~. , . . . , , .= .,: ..... , v ~ ted; zs O7-2008 . DESCPAMD ; PCT/uS 2007/068 456 :e { . .
Attomey L)ocKet No.. oD7034,00fl80 PET 0.48 mils .
INK 0.1 #lream LDPEIEAA Coextrusion 0.5 mils . Foil 0.35 mils LDPEIEAA blend 0.5 mils LDPEICaG blend 2.5 rnaxls =

. . Example 3 [871 Example 3 is a preferred embodiment of the package 200, descrribed above and illustrated with respect to FIG. 3. The package may be made from film structures noted above, and preferably with respect to Examples 1 andlor 2. Specificaliy, the package 200 may be for medical instruments. Each package may be about 5.25 in. long and about 2.25 in. wxde. The heat seals that are created around fhe perrimeter of the packages are about 0.25 in. wide. Taking into consideration the heat seals, each package would have a total exposed internal surface of about 16,6 in2.

. Examples 4-6 [88J The following table 3 illustrates preferred f lm structures and gauges for a seaiant film layer that is extruded as a monolayer film or coextruded with a second layer, such as a tie or adhestve layer, and is then laminated fo other film layers, such as a barrier layer, another tie or adhesive layer, an optional printed or primer layer, and an abuse layer.
Each of the sealant films is made via a blown extrusion method, although other methods are available, such as cast extrusian. , . ~

ixnip!e Film Materials Gau e 39% DuPont Appeel 2444 2.0 mil 6o~a Ampacet X101499 LLDPE of 4 60% bY weight calcium oxide 1% Am acet sli 7012125 49% 1]uPont Appeel l l84 2,0 rnil S 54 /a Ampacet X101499 LLDPE ;of = , ; 60 /Q by weight calcium oxide l% Am acet sli 7012125 59% DuPont Appeel 1181 2.5 mil 40% Ampacet X101499 LLDPE of ~
60/~ by welght calciun'1 oxide 1% Am acet sli 701 2125 27133 1 1 -a2M2OO8 , ....+ : , . ... ...... . . .: ,,, . ~
~ . T/US 20071066 456 ~rinted; 28-07-20O8 DESCPAMD PG
. Attorney UoCKet No.: 007034.oooso . . , 2s [891 After the sealant filrns are made using blown extrusion, the films should be wrapped immediately with a moisture barrier material to avoid being contaminated by moisriure in the atmosphere. .
Example 7 [90] Table 4 illustrates an embodzment of the present invention, whereby the sealant film layer, described above as Example 4, is laminated to other film layers to form a sealant film structure. .

~

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29 .

Film Lar^~er Materials ~iJ!

r^u ^ r~ ~^.+~r~inner heat sealant Exam le 4 described above, 2~0 mils layer p ' .
First tie or adhesive . . 0.5 mils la er E~LL`PE Coextruslon Y
Barrier layer Foil 70 auge Second txe or EAA/LDPE Coextrusion 0.5 mils adhesive layer Print la er Ink 0.1 #Iream Outer abuse layer PET 48 auge Example S

[91J Table 5 illustrates an embodiment of the present invention, urhereby the sealant film layer, described above in Example 5, is laminated to other film layers to form a sealant Film structure.

. , Film. Layer . Materials Inner heat sealant Exam le 5 de cribed above. .2.0 mils la er . p ' s First tie or adhesiveEAAILDPE Coextrusion 0.5 mils 1 ayer Barrier la er Foil 70 gau e Second tie or EA~EB,pE Coextrusion ~~~ mils adhesive layer Print layer Ink 4.1 #lream Outer abuse layer PET 48 gau e . Exarnple 9 [92j Table 6 illustrates an embodiment of the present invention, whereby the sealant f lm layer, described above in Example G, is laminated to other f lm layers to form a sealant film structure.

, TABLE 6 .
Film La er Materials , Z.5 mils ,, . Inner heat sealant Example 6, described above.
layer e , 29/33 1 1 ~o2-2oo8 t .. . , : .. . : ,, :, .., ,_, ... ....... . . . .
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xnorney uocket Nv.: 007034.OOOSO . ~ , FIrSt tXe or adheslVe a.~ n11~s EAAILI~PE Coextrusion , la er Barrier layer Foil 70 auge Second tie or . 0.5 mils ' EAAJLDPE Coextrusion, adhesxve layer Print layer Tnk 0.1 #lream Outer abuse layer PET 48 gauge . . - Example l l [931 Alternatively, each of the sealant film structures, described ab ve with reference to r Examples 7-9, can be heat-sealed to identical film structures to provide packages having spaces therein for moisture-sensitive products, such as pharmaceutical ox nutraceutical products.

Example 12 [94] Table 7 illustrates an alternative filrn structure that may be heat sealed to the sealant film structures described above with reference to Examples 7-9. The sealant film structures can be heat seated ta a base structure having a heat sealant layer comprising an amount of a desiccant material.

,a .
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. lnner heat sealant ExamPle 6, described above. ~~ 5 mils la er 4 Extrusion coating APPEEL~ 0.5 mils Forming la er .. PVG 6 mils Earrier layer .ACLAR 1 mil [951 Alternatively, the forming layer of PVC and the barrier layer of ACL.AR
may be I switched. In addition, the extrusion coating layer of APPEELO m,ay be replaced with an adhesive layer such that the inner heat sealant layer rnay be adhesive laminated to the , remainder of the f lm structure. . -Example 15 [96] In an embodiment of the invention, a medical system comprises a drug eluting stent packaged in a moisture-scavenging pouch in an envaron.rnent of relative humidity greater than approximately 90%. A TAXtJST'" (Boston Scientihc, Natick, MA) , paclitaxel-eluting stent is placed in a moisture-scavenging pouch comprising two multilayer films that are folded and sealed along three sides, comprising the materials listed in Table 8. The pouch can be envisioned as similar to the package 200 illustrated in Fig. 4. Table S includes the referen,ce numbers corresponding to each layer, except for the print layer. The peelable HDPE layer is the product contact layer l 10.

: [971 with the paclitaxel-eluting stent inside the rnoisture-scavenging pouch, the final side is sealed and the relative humidity inside the pouch initially can be at least 90% in an . embodiment. Moisture diffuses through the peelable HDPE layer 11 Oa and is quxckly . absorbed by the molecular sleve desiccant in the first moisture scavenging layer 112.
At a time of 36 hours after the stent is sealed in the pouch, the relative humidity of the , air surrounding the stent inside the pouch is less than about 20%. - Calciurn oxide is provided in the second moisture-scavengxng layer 1 14 as a backup layer if the.
molecular sieves. become saturated with moisture. The calcium oxide will also bind any water naolecules that diffuse in from the ambient atmosphere through the pouch seal or . , the polyester abuse layer 1 20, the EAAILDPE adhesive layer 118, and the foxl barrier layer 116. After 3 months stored in ambient conditions, the relative humidity inside the . , . {
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pouch is less than approximately 20%. In addition, after 1 year and after 2 years, the relative humidity of the air surrounding the paclitaxel-eiuting stent is less than about 20%. The stent is rnaintained in an environment that limits moisture-driven degradation of the paclitaxel, extending its shelf life to over two years.

F'YXm LaYer, Materrals R...ef # Gau~e lnner heat sealant Peelable ~IPDE 11'0 0'S mils layer First moisture Molecular sievelLDPEIEAA 11 2 1.5 mils scavenging layer Coextrusion ~
Second moisture Galcium oxidelLDPEIEAA 114 1.5 mils scavenging layer Coextrusion .
Barrierla er Foil 116 35 au e Tie or adhesive layer EA.AILDPE Coextrusion 11 S 0.5 mils Print layer - Ink Not shown 0.1 #Iream Uuter abuse layer Polyester I20 48 gauge [98] An embodirnent of the invention is a method to increase the sterilization of a drug . eluting stent in a multilayer film package, such as the moisture-scavenging pouch of Example 15 described in Table 8. The method comprises exposure of the drug eluting stent, a sirolimus-eluting CYPHERTM stent (Cordis Corporation, Miam.i Lakes, FL), in an open pouch to a concentration of ETO of approxirnately at least 500 mglL in an atmosphere of at least about 60% relative humidxty at a temperature of approxirnately I 25 F for about an hour. The ETa gas is substantially evacuated and the moisture-scavengrng p uch is then sealed, providing a relative humidity of the atmosphere around the drug eluting stent in the pouch of about 60% at a ftrst tinae.
Moisture diffuses through the peelable HDPE layer 110 and is quickly absorbed by the molecular sieve desiccant in the first moisture scavenging layer 11 2, j99J At a time of 36 hours after the sirolimus-eluting stent is sealed in the pouch, the relative humidity of the air surrounding the stent inside the pouch is less than about 24%.
, . Calcium oxide is provided in the second moisture~scavenging layer 114 as a backup layer if the molecular sieves become saturated with water. The calciurn oxide will also : .. .. :4 32/33 ...1 :.1 rO2....,21CO8 +M
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bind water moiecules that diffixse in frorn the ambient atmosphere through the pouch seal or through the polyester abuse layer I20, the EAAILDPE adhesive layer i I
8, and the foil barrier layer I 1 b. After 6 months stored in ambient conditions, the relative humidity inside the pouch is Iess than approximately Zo%. In addition, a:fter 18 months and after 30 months, the relative humidity of the air surrounding the sirolimusWeluting stent is less than about 20%. This method results in both increased sterilization of the CYPHERTM stent by ETD gas in a humid environment and extended shelf life of the t packaged stent due to the rnoisture-scavenging properties of the muxti-layer film package.

[100] It should be understood that various changes and modif cations to the presently preferred embodiments described herein will be apparent to those skilled in the art.
, Such changes and modifications may be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. It is, therefore, intended that such changes and modifications be covered hy the appended claims.

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Claims (12)

1. A package comprising a first film structure and a second film structure, the first film structure comprising:

a first barrier layer, a first desiccant layer, a first product contact layer, and a first non-aqueous adhesive;
the second film structure comprising:

a second barrier layer, a second desiccant layer, a second product contact layer, and a second non-aqueous adhesive product contact layer, wherein the first barrier layer comprises one or more materials selected from the group consisting of: polyvinylidene chloridemethyl acrylate copolymer, high density fluorocarbon polymer, cyclo-olefin copolymer, metal foil, nylon, high density polyethylene, oriented polypropylene, cast polypropylene, metallized oriented polypropylene, and metallized polyester, and wherein the first desiccant layer comprises a chemical desiccant, and wherein the first desiccant layer and the second desiccant layer combined have the capacity to alter the relative humidity in the interior of the package from more than approximately 50% to less than approximately 20% within a time period of less than approximately 36 hours.

2. The package according to claim 1 wherein the first desiccant layer comprises approximately 20 -40% by weight desiccant and approximately 60 - 80% by weight polymeric material.

3. The package according to either claim 1 or claim 2 wherein the second desiccant layer comprises approximately 20 -40% by weight desiccant and approximately 60 - 80%
by weight polymeric material.

4. The package according to any of claims 1 - 3 wherein the first barrier layer has a thickness of no greater than approximately 75 microns.

5. The package according to any of claims 1 - 4 wherein the first desiccant layer further comprises a molecular sieve desiccant.

6. The package according to claim 5 wherein the second desiccant layer comprises a chemical desiccant and a molecular sieve desiccant.

7. The package according to any of claims 1 - 6 wherein the product contact layer comprises one or more materials selected from the group consisting of polyvinylchloride, cyclo-olefin copolymer, high density polyethylene or a blend of cyclo-olefin copolymer and high density polyethylene.

8. The package according to any of claims 1 - 7 wherein the first film structure is sealed to the second item structure.

9. The package according to any of claims 1 - 8 wherein the chemical desiccant of the first desiccant layer comprises one or more materials selected from the group consisting of calcium oxide, magnesium oxide, strontium oxide and aluminum oxide.

10. The package according to claim 5 wherein the molecular sieve desiccant of the first desiccant layer comprises crystalline alumino-silicate with a pore size of no more than approximately 4 angstroms.

11. The package according to any of claims 1 - 10 wherein the package contains a moisture sensitive drug eluting stent in the interior of the package.

12. The package according to claim 1, wherein the first desiccant layer and the second desiccant layer combined have the capacity to alter the relative humidity in the interior of the package from more than approximately 50% to less than approximately 10% within a time period of less than approximately 36 hours.