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THATTHE TOUT UNTUK TAUS IN20170304150A1 AN AREA MARIA MAI MARI CHANTHI ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2017/ 0304150 A1 Gumudavelli et al. ( 43 ) Pub . Date: Oct. 26 , 2017

( 54 ) STABLE PACKAGING SYSTEM FOR A61K 31/ 22 ( 2006 . 01 ) MOISTURE AND OXYGEN SENSITIVE B01J 20 / 10 (2006 .01 ) PHARMACEUTICAL DOSAGE FORMS A61K 47/ 02 ( 2006 .01 ) B65D 81/ 26 (2006 .01 ) (71 ) Applicant: Ascent Pharmaceuticals , Inc ., B65D 75 / 36 ( 2006 .01 ) Hauppauge , NY (US ) (52 ) U . S . CI. CPC ...... A61 ) 1 /035 (2013 .01 ) ; B650 81/ 268 (72 ) Inventors : Sridhar Gumudavelli, Hauppauge, NY ( 2013 .01 ) ; B650 81/ 264 ( 2013 .01 ) ; B650 (US ) ; Sudhakar Vidiyala , Hauppauge , 75 / 368 ( 2013 .01 ) ; A61K 31/ 22 ( 2013 .01 ) ; NY (US ) ; Madhava Reddy , B01J 20 / 103 ( 2013 .01 ) ; A61K 47 /02 Hauppauge , NY (US ) ( 2013 .01 ) ; A61K 31 /352 (2013 .01 ) ; B01J ( 21 ) Appl. No. : 15 /490 ,216 2220 /66 (2013 .01 ) (22 ) Filed : Apr. 18 , 2017 (57 ) ABSTRACT Related U . S . Application Data The invention describes a blister packaging system , and method of making the system , capable of establishing and (60 ) Provisional application No . 62/ 324 ,472 , filed on Apr. maintaining arid and anaerobic conditions for packaging 19 , 2016 . pharmaceutical products that are sensitive to oxygen and /or moisture . The blister packaging system encompasses , for Publication Classification example , a scaffold of several interconnected cavities (51 ) Int. Cl. intended for product and one or more reservoirs comprising A61) 1 /03 ( 2006 .01 ) an oxygen scavenger and /or a desiccant. Furthermore , the B650 81/ 26 ( 2006 . 01) concentration of the components is maintained at a level that A61K 31/ 352 ( 2006 .01 ) prevents establishment of equilibrium conditions.

Channel Product Cavity

Drug product Patent Application Publication Oct. 26 , 2017 US 2017 / 0304150 A1

Figure 1

Channel Drug Product Cavity * ** * Drug product

Desiccant/ Scavenger US 2017 /0304150 A1 Oct. 26 , 2017

STABLE PACKAGING SYSTEM FOR invention provides a package wherein the oxygen scavenger MOISTURE AND OXYGEN SENSITIVE is selected from the group consisting of organic , inorganic , PHARMACEUTICAL DOSAGE FORMS metallic , non -metallic , and enzymatic in nature . The inven tion provides a package where in the desiccants is selected [ 0001] This application claims the benefit of U .S . Provi from the group consisting of organic desiccants , inorganic sional Application Ser . No. 62 /324 , 472 , filed Apr. 19, 2016 , desiccants , uncoated polymers , coated adsorbent polymers , the entirety of which is incorporated herein by reference . and combinations thereof . The invention provides a package wherein the frangible lidding has moisture barrier proper BACKGROUND OF THE INVENTION ties . [0002 ] The present invention describes a blister packaging [0007 ] The invention provides a blister package for an system , and method of making the system , capable of oxygen and / or moisture sensitive pharmaceutical product establishing and maintaining arid and anaerobic conditions comprising: (i ) a shaped film comprising : (A ) a plurality of for packaging pharmaceutical products that are sensitive to cavities configured to each hold a single unit dose of the oxygen and /or moisture . The blister packaging system pharmaceutical product , and ( B ) at least one airflow channel, encompasses, for example , a scaffold of several intercon and ( C ) at least one reservoir ; wherein the at least one nected cavities intended for product and one or more reser airflow channel connects each of the plurality of cavities to voirs comprising an oxygen scavenger and / or a desiccant . the at least one reservoir ; ( ii) a frangible lidding sealed to the Furthermore , the concentration of the components is main shaped film so that the unit dose is substantially confined tained at a level that prevents establishment of equilibrium between said frangible lidding and said at least one cavity ; conditions . ( iii) an absorbent confined between the reservoir and the [0003 ] All references cited herein are incorporated herein frangible lidding ; ( iii ) optionally a backing film ; and ( iv ) by reference in their entireties . single unit doses of an oxygen and/ or moisture sensitive pharmaceutical product confined between the cavities and BRIEF SUMMARY OF THE INVENTION the frangible lidding . The invention provides a package [ 0004 ] The invention provides a packaging system for a wherein the absorbent comprises a desiccant and an oxygen pharmaceutical product that is sensitive to oxygen and / or absorber, wherein the desiccant is selected from the group moisture comprising : a blister pack comprising: (i ) a blister consisting of silica gel, clay desiccants , calcium sulfate , sheet comprising of an array of interconnected cavities , calcium oxide , zeolite , activated alumina , connected through channels that allows the exchange of air activated charcoal, and combinations thereof, and the oxy between them ; (ii ) wherein one ormore of the cavities serve gen absorber is selected from the group consisting of iron as a reservoirs holding an oxygen scavenger and / or a des oxidase , glucose oxidase , sodium sulfate , potassium chlo iccant at concentrations high enough to provide higher ride , , ammonium sulfate , calcium chlo equilibration time for oxygen and / or moisture ; ( iii) further ride , sodium phosphate , calcium phosphate , wherein one or more of the cavities comprise at least one chloride , and combinations thereof. pharmaceutical product that is sensitive to oxygen and / or [0008 ] The invention provides a package wherein the moisture ; and ( iii ) a frangible lidding sealed to the sheet absorbent comprises a moisture sensitive color indicator to protecting the product in the cavity . The invention provides indicate when the desiccant is no longer operable. The a package wherein the pharmaceutical product contains an invention provides a package wherein the cavities are inter active that comprises at least one as a part of chemical connected by airflow channels . The invention provides a groups . The invention provides a package , where in the package wherein the pharmaceutical product is selected pharmaceutical products is an active that is selected from the from the group consisting of , , group consisting of , drobinol, dronabinol, , , epinephrine , , 8 - , , and combinations esterified estrogen , , , acetamino thereof. phen , , danofloxacin , , penicillin , [ 0005 ] The invention provides a package, wherein the cyclosporine , methyldopate , , , vera pharmaceutical product is selected from the group consisting pamil , , chlorothiazide , , selegi of statins , lovastatin , simvastatin , fluvastatin , atorvastatin , line , , vitamin A , vitamin B , vitamin C , L - cys pitavastatin , and combinations thereof. The invention pro teine, L - , and combinations thereof. The vides a package , wherein the pharmaceutical product is invention provides a package wherein the shaped film com selected from the group consisting ofmorphine , hydromor prises polyvinyl chloride , polyvinylidene chloride , polycar phone, promethazine , dopamine , epinephrine , norepineph bonate , polyester , copolyester , acrylonitrile , low density rine, esterified estrogen , ephedrine , pseudoephedrine , acet polyethylene , polypropylene , or a combination thereof . The aminophen , ibuprofen , danofloxacin , erythromycin , invention provides a package wherein an active pharmaceu penicillin , cyclosporine, methyldopate , cetirizine , diltiazem , tical ingredient in the pharmaceutical product is an active , mexiletine , chlorothiazide , carbamazepine , sele that is selected from the group consisting of cannabinoids , giline, oxybutynin , vitamin A , vitamin B , vitamin C , L -cys drobinol, dronabinol, d - tetrahydrocannabinol, cannabidiol, teine , L - tryptophan , and combinations thereof. statins, lovastatin , simvastatin , fluvastatin , atorvastatin , [ 0006 ] The invention provides a package wherein the pitavastatin , and combinations thereof. blister sheet that has light and moisture protectant proper ties. The invention provides a package wherein the blister BRIEF DESCRIPTION OF SEVERAL VIEWS OF sheet is made ofmaterials selected from the group consisting THE DRAWINGS of polyvinylchloride , polyvinylidene chloride , polycarbon [0009 ] The invention will be described in conjunction with ate , polyester, copolyester , acrylonitrile , low density poly - the following drawings in which like reference numerals , polypropylene, and combinations thereof. The designate like elements and wherein : US 2017 /0304150 A1 Oct. 26 , 2017

[0010 ] FIG . 1 shows an orthogonal view of an example of subject is an elderly human . In another embodiment, the the blister pack component of the packaging system . subject is a human adult . In another embodiment, the subject is a human child . In yet another embodiment, the subject is DETAILED DESCRIPTION OF THE a human infant . INVENTION [ 0016 ] As used herein , the phrase " pharmaceutically [0011 ] The present invention describes a blister packaging acceptable ” means approved by a regulatory agency of the system capable of establishing and maintaining arid and federal or a state government, or listed in the U . S . Pharma anaerobic conditions for packaging pharmaceutical products copeia , European Pharmacopeia , or other generally recog that are sensitive to oxygen and / or moisture . The blister nized pharmacopeia for use in animals , and more particu packaging system encompasses, for example, a scaffold of larly , in humans . several interconnected cavities intended for product and one [0017 ] As used herein , the terms " prevent, " " preventing ” or more reservoirs comprising an absorbent which com and " prevention " in the context of the administration of a prises an oxygen scavenger and /or a desiccant . The concen therapy to a subject refer to the prevention or inhibition of tration of the components is maintained at a level that the recurrence , onset, and/ or development of a disease or prevents establishment of equilibrium conditions . condition , or a combination of therapies ( e . g ., a combination [ 0012 ] The term “ oxygen -sensitive pharmaceutical prod of prophylactic or therapeutic agents ) . uct” refers to any pharmaceutical product containing a [0018 ] As used herein , the terms “ therapies ” and substance that is prone to react with oxygen under normal " therapy ” can refer to any method ( s ) , composition ( s ) , and / or ambient conditions (about 5° C . to about 40° C . ) . The agent( s ) that can be used in the prevention , treatment and / or reaction may involve the addition of oxygen to the sub management of a disease or condition , or one or more stance , removal of hydrogen from the substance , or the loss symptoms thereof. or removal of one or more electrons from a molecular entity [0019 ] As used herein , the terms “ treat, ” “ treatment, ” and in the substance , with or without concomitant loss or " treating” in the context of the administration of a therapy to removal of protons. It can also involve indirect processes a subject refer to the reduction or inhibition of the progres where, for example , an oxidizing agent ( e . g ., peroxide , sion and/ or duration of a disease or condition , the reduction superoxide ) is generated which oxidizes a substance in the or amelioration of the severity of a disease or condition , pharmaceutical product. and / or the amelioration of one or more symptoms thereof [ 0013 ] The term “ moisture -sensitive pharmaceutical prod resulting from the administration of one or more therapies . uct” refers to any pharmaceutical product containing a substance that is prone to degradation , crystal form conver Blister Packs sion , physical instability and /or structural alteration under [ 0020 ] The term Blister packs herein is taken to mean normal ambient conditions when water , water vapor and /or packaging comprising at least two sheets , films, or foils humidity are present. Thus, any pharmaceutical product which are firmly bonded to one another and which contain containing a substance having a propensity for uptake of cavities for the accommodation of the pharmaceutical prod moisture, and the uptake unacceptably affects the physical uct to be packed . Blister packs usually consist of a thermo properties or stability (dissolution , disintegration , hardness , formed plastic sheet or film ( cavity sheet , blister sheet, or friability ) of the finished form of the product , is an example shaped film ) for the accommodation of the solids , which , of a moisture -sensitive pharmaceutical product. The term after filling , is firmly bonded , e. g ., heat- sealed , to a second also refers to any pharmaceutical product containing a sheet , film or foil ( cover sheet, frangible layer , film or foil ) , substance affected by hydrolysis , whereby for example, a which usually consists of an aluminium foil and /or plastic bond in the substance is cleaved by addition of hydrogen and sheet or film . The packaged pharmaceutical product s can be hydroxide ions (ions resulting from the split of a water pushed through the cover sheet, frangible layer , film or foil molecule ) . by pressure on the cavity sheet, film or foil and removed [ 0014 ] An amount is " effective” as used herein , when the individually from the blister pack . Blister packs are therefore amount provides an effect in the subject. As used herein , the also known as push - through packs . If “ pushing - through ” the term “ effective amount” means an amount of a compound or cover sheet, film or foil is not possible owing to the shape , composition sufficient to significantly induce a positive size and / or strength of the solids contained , the blister packs benefit , including independently or in combinations the can also be opened by slitting open the cover sheet, film or benefits disclosed herein , but low enough to avoid serious foil using a sharp object, for example using the finger nail . side effects , i. e ., to provide a reasonable benefit to risk ratio , However, the term “ blister pack ” is not restricted thereto , but within the scope of sound judgment of the skilled artisan . also encompasses special embodiments , such as, for For those skilled in the art, the effective amount, as well as example , child - proof modifications , such as , for example , dosage and frequency of administration , may easily be those in which it is necessary to carry out two different determined according to their knowledge and standard meth opening operations whose sequences are intended to be odology of merely routine experimentation based on the beyond the intellectual capacity of children (such as so present disclosure . called " peel- push systems” ) , or embodiments in which the [ 0015 ] As used herein , the terms “ subject" and " patient” cover sheet, film or foil is not punctured , but instead peeled are used interchangeably . As used herein , the term “ patient” off before removal of the solids contained . refers to an animal , preferably a mammal such as a non [ 0021 ] Blister packs are the preferred primary packaging primate ( e . g . , cows, pigs , horses , cats , dogs , rats etc . ) and a means for solid pharmaceutical administration forms. primate ( e . g . , monkey and human ) , and most preferably a Advantages are that the administration forms can be human . In some embodiments , the subject is a non - human removed individually and thus without contamination of the animal such as a farm animal ( e . g . , a horse, pig , or cow ) or other administration forms, which are furthermore contained a pet ( e . g . , a dog or cat ) . In a specific embodiment , the in sealed cavities , the administration forms are separated US 2017 /0304150 A1 Oct. 26 , 2017 from one another (meaning that mutual interaction , such as, that is attached to the shaped film in a manner that permits for example , abrasion or sticking, are basically prevented ) . the consumer to easily tear it away from each cavity , thereby [0022 ] further important function of blister packs is gaining access to the single unit doses. protection of the pharmaceutical administration forms con 10027 ] In an exemplary embodiment, the blister pack tained therein against harmful environmental influences , comprises a frangible lidding which is sealed or affixed to such as light, gases , in particular oxygen , and against the shaped film such as by heat induction , for instance , so moisture . Since blister packs are usually accommodated in that the single unit doses of pharmaceutical product are folding cartons, which are not effective barriers against substantially confined between the wells of the cavities and moisture and gases , the crucial protective action in the case the frangible lidding . of solid pharmaceutical administration forms packaged in [0028 ] A suitable blister pack , e . g . for a pharmaceutical blister packs (primary packaging means ) and folding cartons composition or combination of the invention , comprises or ( secondary packaging means) arises through the blister is formed of a top foil or frangible layer (which is breachable packs. by the tablets ) and a bottom part ( which contains pockets for [ 0023] Various plastic sheets or films, such as, for the tablets ) . The top foil or frangible layer may contain a example , polyvinyl chloride (PVC ) , polyvinylidene chloride metallic foil , particularly an aluminium or aluminium alloy (PVDC ) , high - density polyethylene (HDPE ) , polypropylene foil ( e . g . having a thickness of 20 um to 45 um , preferably (PP ), polyethylene terephthalate (PET ) , polycarbonate , each 20 um to 25 um ) that is coated with a heat- sealing polymer of which have different material properties may be used in layer on its inner side ( sealing side ) . The bottom part may the blister packs of the invention . Although the selection of contain a multi - layer polymer foil ( such as , e . g . , poly ( vinyl a material of relatively low permeability for moisture and /or chloride ) (PVC ) coated with poly ( vinylidene chloride ) oxygen or the use of composite sheets or films made from ( PVDC ) ; or a PVC foil laminated with poly ( chlorotriflouro these materials , such as , for example , PVC /PVDC , PVCI ethylene ) (PCTFE )) or a multi- layer polymer -metal -polymer HDPE , optionally also together with further polymers as foil ( such as, e . g . , a cold - formable laminated PVC /alu barrier layer, such as , for example , cycloolefin copolymer minium /polyamide composition ) . ( COC ), or special polyhalogenated polymers, such as poly [0029 ] Aluminium foil, which has low water permeability, chlorotrifluoroethylene (PCTFE ) Aclar® , ( PVC / PCTFE , is usually employed for sealing blister packs, such as in the PP /COC ( for example Polybar® ) PVC / COC /PVDC com frangible layer. Low water permeability is not necessary in posite sheets or films) , enables the ingress ofmoisture to be the pack according to the invention , meaning that other reduced to a certain degree , it does not prevent it completely . materials can also be employed for sealing the blister packs . [0024 ] Suitable for use for the manufacture of blister This enables the use of plastic sheets or films as cover sheet packs which are suitable for the pack according to the or film , where sheets or films made from the same material invention are all plastic sheets or films which can be as the cavity sheet or film can also be used . Single -material converted into blister packs in corresponding plants , in packaging of this type is particularly advantageous since it particular thermoforming plants . Examples of plastic sheets can be recycled without prior separation of cavity sheet or and films which are suitable for the manufacture of blister film and cover sheet or film , which is particularly desired for packs are polyvinyl chloride ( PVC ) , polyvinylidene chloride environmental protection reasons . On use of plastic sheets or ( PVDC ), high -density polyethylene (HDPE ) , polypropylene films as cover sheet or film , water vapour present in the (PP ), polyethylene terephthalate (PET ), polycarbonate , cavities of the blister pack can also be removed through the cycloolefin copolymer (COC ) , special polyhalogenated cover sheet or film , which advantageously increases the polymers , such as polychlorotrifluoroethylene (PCTFE ) drying rate of the pharmaceutical administration forms con Aclar® , and composite sheets or films made from these tained in the blister pack . If , in addition , a plastic sheet or materials , such as , for example , PVC /PVDC , PVC /HDPE , film of very low material thickness is used , a further increase PVC /PCTFE , PP /COC (Polybar® ) PVC /COC /PVDC , par in the drying rate and easier removal of the solid pharma ticularly suitable are PVC , PVDC , HDPE , PP , PET and ceutical administration form contained in the blister pack composite sheets or filmsmade from these , very particularly arise , since this can be pushed through more easily , besides suitable PVC , PP, and PET. The plastic sheets or films can reduced material usage . be employed as cavity sheet or film and / or as cover sheet or [0030 ] To ensure a long storage period especially under film . The cavity sheet or shaped film at least preferably hot and wet climate conditions an additional overwrap or consists of a plastic sheet or film . pouch made of a multi - layer polymer- metal- polymer foil [0025 ] Plastic sheets or films of low thickness are prefer ( e . g . a laminated polyethylen /aluminium /polyester compo ably and advantageously employed for the manufacture of sition ) may be used for the blister packs . the blister packs . The plastic sheets or films used as cavity [0031 ] Blister cards can , for example , contain a foil back sheet or film usually have a thickness of 10 to 500 um , ing as a barrier. Blister cards or packaging can include , for preferably 15 to 300 um , particularly preferably 15 to 100 example , triplex blister film of different types, such as um , very particularly preferably 15 to 50 . standard and high barrier films, including , for example , [0026 ] The blister pack may also include a frangible triplex Flexafarm Sbc ( e . g ., PVC 250 my+ PE 25 my + PVDC lidding, affixed to the shaped film , so that the single unit 150 g/ mq sbc grade) and Aquaba - PVC ( e .g ., PVC 250 dose of the pharmaceutical product is substantially confined my + AQUABA 160 g /mq ) , Aclar, Alu - Alu formats , triple between the frangible lidding and the cavity . The frangible layer blister foil (OPA ) with soft tempered aluminium in lidding is preferably made from aluminum foil sufficiently central position , other layers PVC and polyamide , and new thin so as to enable a consumer to push the single unit dose generation multilayer blister combined materials . through it by pressing on the underside of the cavity , or it [0032 ] The article may further comprise a label or package may be made from an aluminum foil laminate ( i . e . , layers of insert, which refer to instructions customarily included in aluminum , polyethylene terepthalate (PET ) and / or paper ) commercial packages of therapeutic products , that may US 2017 /0304150 A1 Oct. 26 , 2017 contain information about the indications, usage , dosage , calcium sulphate , activated bentonite clay , water - absorbing administration , contraindications and /or warnings concern clay , molecular sieve and any mixtures thereof. ing the use of such therapeutic products . In one embodiment , [ 0038 ] Absorbents which may be present are in principle the label or package inserts indicates that the composition any type of desiccants , i . e . moisture -binding binders . Des can be used for any of the purposes described herein . iccants may include chemical substances which form 10033 ] For most situations , but not all, the blister pack will hydrates with water. Examples of chemical substances of include a plurality of cavities , a plurality of airflow channels this type are anhydrous salts , which tend to absorb water or ( at least one airflow channel per cavity ) , which together moisture and in the process form a stable hydrate . The permit oxygen and moisture trapped in the plurality of moisture is bound and liberation thereof is prevented by a cavities to easily pass out of the cavities , into the plurality chemical reaction . of airflow channels and through the plurality of airflow [ 0039 ] Desiccants may contain substances which are reac channels to the reservoir comprising the absorbent. In some tive . The substances react with water ormoisture by forming embodiments , however, there may even exist a plurality of a new substance . The newly formed substances are normally airflow channels for every cavity in the blister . stable at low temperatures , which is only reversible with [ 0034 Where there is a concern that the single unit doses expenditure of high energy . Desiccants of this type are of inside the cavities in the blister pack may be too principally used for drying solvents and as water- absorbent easily accessed by a child , embodiments of the invention material in the case of polymers which themselves have to may also include a hard plastic “ shell pack ” container , remain in a reduced -moisture state . configured to receive , cover and protect the blister pack from [0040 ] Desiccants may bind the moisture by physical direct access until the blister pack is extracted from inside adsorption . The desiccant contains particles having fine the shell pack . In this alternative configuration , the blister capillaries into which the moisture is drawn . The pore size pack may be inserted into the shell pack , and the shell pack of the capillaries and the density thereof in the desiccant sealed inside the sealed outer container during the package determine the absorption properties . Examples of desiccants manufacturing stage . of this type are molecular sieves, silica gels , certain syn thetic polymers . Moisture Absorbing Materials [0035 ] A desiccant is any drying agent that removes Oxygen Absorber moisture from the air . Desiccants include , but are not limited [0041 ] In the pharmaceutical packaging systems described to , silica gel , clay desiccants, calcium sulfate , calcium herein , oxygen absorbers absorb and remove oxygen from chloride , calcium oxide , zeolite , activated alumina , activated all components of the system . Oxygen absorbers are con charcoal and combinations thereof. However, other vapor or templated to be in any size or shape including sachet , pouch , moisture absorbing mechanisms are not beyond the scope of capsule, label, strip , patch , cartridge, lining , sticker , etc . , that the present invention . Other vapor or moisture absorbing is placed inside of the reservoir , but can also be integrated materials include desiccants made from inorganic materials to the primary packaging. In some embodiments , the oxygen such a zeolites and aluminas . Such inorganic materials of absorber is in the form of a capsule . vapour or moisture absorbing materials have high water [0042 Suitable materials for oxygen absorbers include absorption capacities and favourable water absorption iso metal- based substances that remove oxygen by reacting with therm shapes . The water absorption capacity of such mate it by chemical bonding , generally forming a metal oxide rials typically varies from 20 to 50 weight percent. In the component. Metal- based substances include elemental iron preferred embodiment, the absorbing material is a MINI- as well as iron oxide , iron hydroxide , iron carbide and the PAXTM supplied by Multisorb Technologies in the United like . Other metals for use as oxygen absorbers include States and Silgelac in Europe ( silica gel packaged inside nickel, tin , copper and zinc . Metal- based oxygen absorbers TYVEK® , which is a nylon mesh bonded with a micropo are typically in the form of a powder to increase surface area . rous polyurethane ) . Other exemplary moisture absorbing Powder formation of the metal- based oxygen absorbers is by materials include , but are not limited to , alumina , bauxite , any known method including , but not limited to , atomiza anhydrous , calcium sulphate , water- absorbing clay, acti tion , milling, pulverization , and electrolysis . Additional vated bentonite clay , a molecular sieve , or other like mate materials for oxygen absorbers include low molecular rials which optionally include a moisture sensitive colour weight organic compounds such as ascorbic acid , sodium indicator such as cobalt chloride to indicate when the ascorbate , catechol and , activated carbon and poly desiccant is no longer operable . While in the preferred meric materials incorporating a resin and a catalyst. In some embodiment of the present invention , the package is embodiments of the pharmaceutical packaging system , the designed to substantially prevent ingression of water vapor oxygen absorber is a metal -based oxygen absorber. In cer and particulate matter into the enclosed volume, the mois tain instances of the pharmaceutical packaging system , the ture absorbing material is placed within the reservoir in oxygen absorber is an iron -based oxygen absorber. In further order to absorb any residual moisture present in the atmo instances of the pharmaceutical packaging system , the oxy sphere . gen absorber is an iron -based oxygen absorber in the form [ 0036 ). The desiccant should be present in an amount of a canister. sufficient to absorb any residualmoisture inside the package . [0043 ] Oxygen absorbents which can be used in the pres Moreover , the desiccant should be present in an amount ent invention include iron and glucose oxidase . A salt may sufficient to absorb any moisture that possibly ingresses be used as an electrolyte for oxidation of the iron . The iron from the external environment. It is also possible to place the may be hydrogen - reduced iron , electrolytically reduced desiccant inside the reservoir . iron , or chemically reduced iron . Although iron is preferred 10037 ] Preferably the desiccant is selected from the group as the metallic oxygen absorbing agent, it will be appreci consisting of silica gel , zeolite , alumina , bauxite , anhydrous ated that other metals may be used . These are , by way of US 2017 /0304150 A1 Oct. 26 , 2017

example and not limitation , aluminum , copper, zinc , tita diclofenac , alclofenac , bumadizone , etodolac , lonazolac , nium , magnesium , and tin . Also , other elements which can fentiazac, acemetacin , difenpiramide , oxametacin , proglu be used in elemental or partially oxidized form are sodium , metacin , ketorolac , aceclofenac , bufexamac , oxicam , piroxi manganese, iodine, sulfur, and phosphorus. cam , tenoxicam , droxicam , lornoxicam , meloxicam , metho 0044 ] The electrolytic salt may be sodium chloride or any trexate , propionic acid derivatives , ibuprofen , naproxen , other suitable food compatible salt including , but not limited ketoprofen , fenoprofen , fenbufen , benoxaprofen , suprofen , to , sodium sulfate , potassium chloride, ammonium chloride, pirprofen , fiurbiprofen , indoprofen , tiaprofenic acid , oxapro ammonium sulfate , calcium chloride , sodium phosphate , zin , ibuproxam , dexibuprofen , flunoxaprofen , alminoprofen , calcium phosphate , and magnesium chloride . dexketoprofen , fenamates , , , [0045 ] An example of a suitable thermoplastic resin con , , coxibs , celecoxib , rofe taining an oxygen absorber is AmosorbTM 3000 ( available coxib , valdecoxib , parecoxib , etoricoxib , lumiracoxib , nabu from BP Amoco Chemicals ) . Other resins appropriate for the metone , , azapropazone , glucosamine, benzy current invention include those made using ascorbic acid or damine, glucosaminoglycan polysulfate , proquazone , other easily oxidized organic compounds . orgotein , , feprazone , diacerein , morniflumate , tenidap , oxaceprol, chondroitin sulfate, feprazone , dipyro Coloring Agents cetyl, acetylsalicylic acid , quinolines , oxycinchophen , gold 100461 Coloring agents can be used to color code the preparations, sodium aurothiomalate , sodium aurotiosulfate , absorbent, for example , to indicate that the absorbent is not auranofin , aurothioglucose , aurotioprol , penicillamine or to be ingested . Suitable coloring agents include, without bucillamine. limitation , natural and / or artificial compounds such as [0051 ] In another embodiment, suitable active pharmaceu FD & C coloring agents, natural juice concentrates, pigments tical ingredients can comprise , such as , for such as titanium oxide , silicon dioxide , iron oxides, zinc example : , natural alkaloids, morphine , oxide, combinations thereof, and the like . opium , hydromorphone , nicomorphine , , dihy [ 00471 Colorants /opacifiers for use in the present inven drocodeine , diamorphine , , papavereturn , tion include organic dyes and their lakes , inorganic colors , phenylpiperidine derivatives , ketobemidone, pethi and natural colors , including water soluble colors and water dine, , diphenylpropylamine derivatives , dextromor insoluble colors ( pigments ) . The compositions of the present amide, piritramide , , bezitramide, invention can comprise from about 0 % to about 10 % by , benzomorphan derivatives, , weight of the flavoring and /or coloring agent, preferably , oripavine derivatives , , morph from about 0 . 1 % to about 5 % , and more preferably from inan derivatives , , , tilidine , trama about 2 % to about 3 % . dol , , and derivatives, acetylsalicylic Pharmaceutical Products that are Sensitive to Oxygen and /or acid , , salicylate , , salicy Moisture lamide , , , morpholine salicylate , dipy [ 0048 ] In exemplary embodiments , the pharmaceutical rocetyl , , , potassium salicylate , guaceti product that is sensitive to oxygen and /or moisture is sal , carbasalate calcium , salicylate , pyrazolones, selected from the group consisting of morphine, hydromor phenazone , metamizole sodium , aminophenazone , propy phone , promethazine , dopamine , epinephrine , norepineph phenazone , nifenazone , anilides , , phenacetin , rine, esterified estrogen , ephedrine , pseudoephedrine , acet bucetin , propacetamol, other analgesics and antipyretics , aminophen , ibuprofen , danofloxacin , erythromycin , such as , for example : rimazolium , glafenine, floctafenine , penicillin , cyclosporine, methyldopate , cetirizine, diltiazem , viminol, , , or . verapamil , mexiletine , chlorothiazide , carbamazepine , sele [ 0052 ] In another embodiment , suitable active pharmaceu giline , oxybutynin , vitamin A , vitamin B , vitamin C , L - cys tical ingredients can comprise anaesthetics, such as, for teine , L -tryptophan , and combinations thereof. example : , diethyl , vinyl ether, halogenated [0049 ] Other Active Pharmaceutical Ingredients may hydrocarbons, , , , include opioids. such as, for example , antitussive expecto , , , , sevoflu rants such as phosphate , codeine phosphate , rane , , , , thiopental , and hydrochloride. In another embodiment, the , anaesthetics , fentanyl, , opioid drugs are analgesics drugs such as , , , , , other morphine , hydromorphone, oxycodone , codeine , levorpha general anaesthetics, such as, for example : , ket nol , meperidine , methadone, oxymorphone, buprenorphine , amine , , , , , fentanyl and derivatives thereof, dipipanone, , etor hydroxybutyric acid , , , , phine, dihydroetorphine , butorphanol, , or salts esters of aminobenzoic acid , metabutethamine, , thereof or mixtures thereof. In one embodiment, the opioid , , , amides , bupiva is morphine , oxycodone , hydrocodone , or a salt thereof. In caine , , , , butanilicaine , cin one embodiment, a morphine salt is morphine sulfate ; an chocaine , , , , levobupiva oxycodone salt is oxycodone HCl; and a codeine salt is caine , esters of benzoic acid , , other local codeine sulfate or phosphate. anaesthetics , such as , for example : ethyl chloride , dyclonine , [ 0050 ] Examples of specific active drug substances suit phenol , or capsaicin . able for use in the pharmaceutical compositions provided [0053 ] In another embodiment, suitable active pharmaceu herein include : anti- inflammatory and antirheumatic active tical ingredients can comprise antimigraine active drug drug substances , such as, for example: butylpyrazolidine , substances, such as, for example : ergot alkaloids , dihydro phenylbutazone , morebutazone , oxyphenbutazone , clof , ergotamine, , , corticoster ezone , kebuzone , acetic acid derivatives and related sub - oid derivatives , flumedroxone , selective ( SHT. sup . stances , indometacin , sulindac , tolmetin , zomepirac , 1 ) , , , , US 2017 /0304150 A1 Oct. 26 , 2017 , , , , other anti sium , , , , preparations , , , , , , , , , , or . , , , , ethyl [0054 ] In another embodiment, suitable active pharmaceu loflazepate , , , , tofisopam , tical ingredients can comprise antiepileptic active drug sub diphenylmethane derivatives, , , car stances, such as, for example : barbiturates and derivatives , bamates , , , , dibenzo , , , barbexa bicyclo -octadiene derivatives, , azaspirode clone , , hydantoin derivatives, , pheny canedione derivatives, , other anxiolytics , such as , toin , amino (diphenylhydantoin ) valeric acid , , for example : , , or . , oxazolidine derivatives, , [0059 ] In another embodiment, suitable active pharmaceu , , derivatives, ethosuxi tical ingredients can comprise and active mide , , , deriva drug substances , such as , for example : barbiturates , pento tives, , carboxamide derivatives , carbam , , , barbital, , azepine , , , fatty acid derivatives , , , , , , valproic acid , , aminobutyric acid , vigabatrin , heptabarbital, , methohexital, hexobarbital, thiopen progabide, tiagabine, other antiepileptics, such as, for tal, ethallobarbital, , proxibarbal , aldehydes and example : sultiame, , , , derivatives, hydrate, , acetylglycinamide , , , , zonis , , , benzodi amide , , , , or beclamide . azepine emepronium derivatives, , , [0055 ] In another embodiment, suitable active pharmaceu , , , , temaze tical ingredients can comprise active drug pam , , , , , substances , such as , for example : tertiary , trihexy efazepam , , piperidinedione derivatives, glute phenidyl, , , , , thimide , , , benzodiazepine , , , , tro related drugs , , , , , patepine , ethers chemically close to , etanau other and , such as , for example :meth tine , ( chloride ), ethers of tropine or tropine aqualone , , , , scopol derivatives , , or . amine, , , , , [ 0056 ] In another embodiment, suitable active pharmaceu , , , , methyl tical ingredients can comprise active drug pentynol, , , , or dip substances , such as , for example : dopa and dopa derivatives , iperonylaminoethanol. levodopa, , , deriva [0060 ] In another embodiment, suitable active pharmaceu tives , , dopamine agonists , , per tical ingredients can comprise active drug golide , dihydroergocryptinemesylate , , pramipex substances , such as, for example : non - selective monoamine ole, , , , , reuptake inhibitors, , , imipramine monoamine , oxidase B inhibitors , , , oxide , , , , , other dopaminergic agents , such as, for example : , , , , , dox , or . epin , , , , , amox [0057 ] In another embodiment, suitable active pharmaceu apine, , , , , tical ingredients can comprise active drug selective serotonin reuptake inhibitors , zimeldine, fluox substances, such as , for example : with ali etine , , , , , fluvox phatic side -chain , , , pro amine , , , mazine, acepromazine , , , chlo inhibitors , isocarboxazid , nialamide , phenelzine , tranylcy rproethazine , phenothiazines with structure , promine , iproniazide , iproclozide , monoamine oxidase A , , , , inhibitors , moclobemide, toloxatone, other , , , , thiopropera such as, for example : oxitriptan , tryptophan , , zine , , , phenothiazines with , , , minaprine , bife structure , , , , pipotiaz melane , , , , , ine , derivatives, , , tianeptine , pivagabine, , , rebox , , , , benperi etine , , , , , dol, droperidol, , derivatives , oxypertine , centrally acting sympathomimetics , such as , for example : , , , deriva amfetamine , dexamfetamine , , metamfet tives , , , , , amine, , , , , derivatives , fluspir , , , , fenetyl ilene , , , diazepines , oxazepines, thiaz line , derivatives , , propentofylline , other epines, , , , , neuro psychostimulants and nootropics , such as, for example leptics, , , , , , , piracetam , deanol, , citi , , , , levo coline , , , , nizofenone , sulpiride , lithium , other , such as , for example aniracetam , , idebenone , , pip , , , , radrol, pramiracetam , , or vinpocetine . , , or . [0061 ] In another embodiment, suitable active pharmaceu [0058 ] In another embodiment, suitable active pharmaceu tical ingredients can comprise anti - dementia active drug tical ingredients can comprise anxiolytic active drug sub substances , such as , for example : anticholinesterases, stances , such as , for example : benzodiazepine derivatives, tacrine , donepezil , rivastigmine , , other anti , , , , potas dementia drugs, , or . US 2017 /0304150 A1 Oct. 26 , 2017

[0062 ] In another embodiment , suitable active pharmaceu fentanyl , beta -hydroxyfentanyl , betameprodine, betame tical ingredients can comprise other nervous system active prodine, betamethadol, betaprodine , bezitramide , drug substances, such as, for example : parasympathomimet bezitramide, boldenone , brolamfetamine, bromazepam , bro ics, anticholinesterases , , pyridostigmine , distig tizolam , bufotenine , buprenorphine , , , mine , ambenonium , choline esters, , , butobarbital, butorphanol, BZP (A2 ) ( 1 - benzylpiperazin ), and other parasympathomimetics, such as, for example , camazepam , , carfentanil , catha edulis , , , or choline alfoscerate . , , chloral hydrate , chlordiazepox [ 0063] Active drug substances used in addictive disorders , ide , chlorhexadol, chlorotestosterone ( same as clostebol) , such as, for example : , , , dis , clobazam , clonazepam , clonitazene, clo ulfiram , calcium carbimide , acamprosate , , nitazene , clorazepate , , clostebol, clotiazepam , buprenorphine, methadone , , , cloxazolam , leaves , cocaine , codeine , codeine and , , , acetylleucine, ganglio isoquinoline alkaloid , codeine methylbromide, codeine- N sides and ganglioside derivatives , , , xalip oxide , codoxime, cyclobarbital (hexemal NFN ) , cyprenor roden , hydroxybutyric acid , or . phine , dehydrochlormethyltestosterone , , deso [ 0064 ] In another embodiment, suitable active pharmaceu morphine , dexamfetamine , , tical ingredients can comprise opium alkaloids and deriva dexmethylphenidate , dextromoramide , dextropropoxy tives, such as, for example : , hydrocodone , phene , diacetylmorphine , diampromide , diazepam , dichlo codeine, opium alkaloids with morphine , , ralphenazone , diethylpropion , , diethyl noscapine , , , , , difenoxin , dihydrocodeine , dihydroetorphine , , , , benpro dihydromorphine , , dimenoxadol, perine , , , , , dimepheptanol , , dimethyltryptamine , , , , bibenzonium , dioxaphetyl butyrate , diphenoxylate , dipipanone , diprenor , , , , , phine , dronabinol, drostanolone , drotebanol, ecgonine, esta , , , , pip zolam , ethchlorvynol, , , ethyl eridione , , , , levodro estrenol, ethylmethylthiambutene , ethylmorphine , propizine , or . ethylmorphine , , , etonitazene , [0065 ] In another embodiment, the active pharmaceutical etorphine, etoxeridine , etryptamine , fencamfamin , fenethyl ingredient may be a substance with abuse potential that line , fenetylline , , , fentanyl, fludi presents a safety risk . Such active drug substance may azepam , flunitrazepam , fluoxymesterone, flurazepam , include : 1 - ( 1 - phenylcyclohexyl) , 1 - ( 2 -phenyl formebolone , fungi and spores of the species psilocybe ethyl) - 4 -phenyl - 4 -acetoxypiperidine , 1 - [ 1 - ( 2 - thienyl) - cy semilanceata , furethidine , gamma hydroxybutyric acid , glu clohexylpiperidine , 1 - [ 1 - ( 2 - thienyl ) cyclohexyl] pyrrolidine , tethimide , halazepam , , heroine , hydrocodone, 1 -methyl - 4 -phenyl - 4 -propionoxy -piperidine , l- phenylcy hydrocodone & isoquinoline alkaloid , hydromorphinol, clohexylamine , l - piperidinocyclohexanecarbonitrile , 2 , 5 hydromorphone, hydroxypethidine , , isobutyl dimethoxy - 4 - ethylamphetamine, 2, 5 -dimethoxyamphet nitrite , , , ketazolam , ketobemidone , amine , - B -( 4 -bromo - 2, 5 -dimethoxyl ) enethylamine ), levamfetamine , levo - , levo -metham 2C - D ( 2 , 5 - dimethoxy - 4 - methylphenethylamine ), 2C — I ( 4 phetamine, , levomoramide , levophenacyl iodo - 2 , 5 -dimethoxy - ), 2C - T - 2 ( 2 , 5 - dime morphan , levorphanol, lisdexamfetamine, loprazolam , lora thoxy - 4 - ethylthiophenethylamine ) , 2C - T - 4 ( 2 , 5 - dimethoxy zepam , lormetazepam , lysergic acid , lysergic acid amide , 4 -isopropyl thiophenethylamine ), 2C - T- 7 (2 ,5 -dimethoxy -4 lysergic acid diethylamide , marijuana , , MBDN (n ) -propylthiophenethylamine ) , 3 , 4- methylene ( N -methyl - 1 - ( 3 ,4 -methylenedioxyphenyl ) - 2 - butanamine ), dioxymethamphetamine, 3 , 4 ,5 - , mCPP ( 1 - ( 3 - chlorphenyl) piperazine ) , mebutamate , meclo 3 ,4 -methylenedioxyamphetamine , 3 ,4 -methylenedioxy - N qualone, medazepam , , MeOPP (1 - (4 -methoxy ethylamphetamine , 3 -methylfentanyl , 3 -methylthiofentanyl , phenyl) piperazine ), meperidine, meperidine intermediate , 4 -brorno - 2 , 5 - , 4 - bromo - 2 , 5 -dime meprobamate , , , mesterolone , metamfe thoxyphenethylamine, 4 -methoxyamphetamine , 4 -methyl - 2 , tamine , , methadone , methadone intermediate , 5 - dimethoxyamphetamine , 4 -methylaminorex ( cis isomer ), , methandienone , methandrolone , meth 5 -MeO - DIPT ( 5 -methoxy - N , N - ), andriol, methandrostenolone, , methcathi 5 -MeO -DMT ( 5 -methoxy - N , N - dimethyltryptamine ), none , methenolone, methohexital, methyldesorphine , meth 5 -methoxy - 3, 4 -methylenedioxyamphetamine , acetorphine, yldihydromorphine , methylphenidate , methylphenobarbital acetorphine , acetyl- -methylfentanyl , acetyl -alpha (mephobarbital ) , methyltestosterone, methyprylone, meto methylfentanyl, acetyldihydrocodeine , , pone, mibolerone, midazolam , modafinil, moramide- inter acetylmethadol, alfentanil, allobarbital, allylprodine , mediate , morpheridine , morphine, morphine methylbro alphacetylmethadol except levo -alphacetylmethadol , alpha mide , morphine methylsulfonate , morphine- N -oxide , ethyltryptamine, alphameprodine, alphamethadol, alphame myrophine , N , N - , , nalor thadol, alpha- methylfentanyl , alpha -methylthiofentanyl , phine , nandrolone , N - ethyl - 1 -phenylcyclohexylamine , alphaprodine, alprazolam , amfepramon , , N - ethyl- 3 -piperidyl benzilate , N - ethylamphetamine , N - hy amineptin , , amobarbital, , dextroam droxy - 3 , 4 -methylenedioxyamphetamine , , phetamine , amilnitrite ( all isomers of the amyl group ) , nicocodine, , nicomorphine, , anabolic steroids, anileridine , aprobarbital, barbital, barbi nitrazepam , N -methyl - 3 - piperidyl benzilate , noracymeth turic acid derivative, BDB ( 3 ,4 -methylenedioxyphenyl ) - 2 adol, norcodeine, nordiazepam , norethandrolone, norlevor butanamine ), benzethidin , benzethidine , benzoylecgonine, phanol, normethadone, normorphine , norpipanone , norpi , benzphetamine , benzylmethylcetone , ben panone, opium , oxandrolone , oxazepam , , zylmorphine, betacetylmethadol, beta -hydroxy - 3 - methyl oxycodone, oxymesterone , oxymetholone , oxymorphone , US 2017 /0304150 A1 Oct. 26 , 2017 para -fluorofentanyl , , paraldehyde , pemoline, pen [ 0070 ] In another embodiment, the active drug substance tazocine, , , peyote , phenadoxone, is associated with abuse syndromes and the active drug phenampromide , phenazocine , , phendimetra substance may , for example , be selected from opioids, CNS zine , , phenobarbital , phenomorphan , pheno , CNS , cannabinoids, nicotine - like peridine, , phenylacetone , pholcodine , pimino compounds, glutamate antagonists , or N -methyl - D -aspartate dine, pinazepam , pipradrole , piritramide , PMMA (NMDA ) antagonists . (paramethyxymethyl amphetamine ), prazepam , prohep tazine, properidine, propiram , psilocybine , psilocine, pyrov [ 0071 ] In another embodiment, the active drug substance alerone , quazepam , racemethorphane , racemoramide , rac is an . Examples of analgesics suitable for use in emorphane , remifentanil , , , the pharmaceutical compositions described herein include, secobarbital, secobarbital, , SPA , stanolone, for example , opioids, natural opium alkaloids, morphine , stanozolol , sufentanil , sulfondiethylmethane , sulfonethyl opium , hydromorphone , nicomorphine , oxycodone, dihy methane , , talbutal, , tenamfet drocodeine , diamorphine, tapentadol, papaveretum , codeine , amine , testolactone , , , phenylpiperidine derivatives , ketobemidone , , fen , TFMPP ( 1 - (3 - triflourmethylphenyl) piperazine ), tanyl , diphenylpropylamine derivatives , dextromoramide, thebacon , thebaine , , thiofentanyl , thiopental, tile piritramide , dextropropoxyphene, bezitramide , methadone , tamine and in combination , tilidine , trenbolone , benzomorphan derivatives , pentazocine , phenazocine , ori triazolam , trimeperidine , vinbarbital, zaleplon , zipeprol, pavine derivatives, buprenorphine, derivatives , zolpidem , or zopiclone . butorphanol, nalbuphine , tilidine , tramadol, dezocine , sali [0066 ] Other suitable examples of active drug substances cylic acid and derivatives , acetylsalicylic acid , aloxiprin , include , for example , alfentanil , allylprodine, alphaprodine , choline salicylate , sodium salicylate , , salsalate , anileridine , , bezitramide , buprenorphine , ethenzamide ,morpholine salicylate , dipyrocetyl, benorilate , butorphanol, clonitazene , codeine , , desomor diflunisal, potassium salicylate , guacetisal, carbasalate cal phine , dextromoramide , dezocine , diampromide , dihydroco cium , , pyrazolones, phenazone , metam deine , dihydromorphine, dimenoxadol , dimepheptanol, dim izole sodium , aminophenazone , propyphenazone, nifena ethylthiambutene , dioxaphetyl butyrate , dipipanone , zone , anilides , paracetamol, phenacetin , bucetin , eptazocine, ethoheptazine, ethylmethylthiambutene , ethyl propacetamol, other analgesics and antipyretics such as , for morphine, etonitazene , fentanyl, , hydrocodone , example , rimazolium , glafenine , floctafenine , viminol, nefo hydromorphone , hydroxypethidine , isomethadone , dextro pam , flupirtine , or ziconotide . propoxyphene, ketobemidone , , levorphanol, [0072 ] In another embodiment, the active drug substance levophenacylmorphan , lofentanil, meperidine , meptazinol, is an opioid . Where an opioid is included as an active drug metazocine , methadone, metopon , morphine , morphine substance , the opioid may comprise naturally occurring 6 - glucuronide , morphine 3 - glucuronide, myrophine , nalbu opioids, synthetic opioids , or semisynthetic opioids . phine, narcine , nicomorphine , norlevorphanol, normetha done , , normorphine, norpipanone, opium , oxy [0073 ] In other embodiment, the active drug substance codone, oxycodeine , oxymorphone, papavereturn , comprises amfetamine, dexamfetamine , lisdexamfetamine , pentazocine , phenadoxone , phenomorphan , phenazocine, metamfetamine, methylphenidate , dexmethylphenidate , or phenoperidine , piminodine, piritramide , propheptazine , combinations thereof. promedol, properidine, propiram , propoxyphene , sufentanil , [ 0074 ] Where an opioid is used as an active drug sub tilidine , tramadol, thebaine , levo - alphacetylmethadol stance , the opioid may be present in any of its crystalline , (LAAM ) , remifentanil , carfentanyl, ohmefentanyl, MPPP , polymorphous , semi- crystalline, and amorphous or prodine , PEPAP, levomethorphan , etorphine , , polyamorphous forms. Furthermore , in another embodi , diphenoxylate , or pethidine. ment, an opioid used as an active drug substance may be [0067 ] Other examples of active drug substances suitable present in one or more forms selected from its crystalline , for use in the pharmaceutical compositions described herein polymorphous, semi- crystalline , or amorphous or polymor include anabolic steroids, cannabis , cocaine, or diazepam . phous forms. [0068 ] In another embodiment, the active drug substance comprises the therapeutic classes including non -steroidal Manufacturing the Package anti - inflammatory substances or antirheumatic active drug substances . In other embodiments , the active drug substance [0075 ] The blister packs of the present invention may be comprises analgesics , opioids, antipyretics, anaesthetics, manufacture using an automatic blister thermoformer antimigraine agents , antiepileptics , anti -parkinson agents , known in the art. In exemplary embodiments , the blister dopaminergic agents , antipsychotics , anxiolytics , sedatives , thermoformer forms the cavities , reservoirs , and the airflow antidepressants , psychostimulants agents , dopamine , nora channels , fills the cavities with tablets /caplets and the res drenaline , nicotinic , alfa -adrenergic , serotonin , H3 antago ervoir with an absorber, covers and seals the blister pack nists used for ADHD or nootropics agents used in addictive with the frangible lidding , and then die - cuts the sealed disorders . blister packs into their desired final marketing configuration . [0069 ] In other embodiments , the active drug substance The sealed blister packs may then be transported to either an comprises therapeutic classes including anaesthetics, cen automatic or manual pouch machine . trally acting analgesics , sedative -hypnotics , anxiolytics, [0076 ] The invention will be illustrated in more detail with appetite suppressants , decongestants , antitussives , antihista reference to the following Examples , but it should be mines , antiemetics , antidiarrheals , and drugs used to treat understood that the present invention is not deemed to be narcolepsy, or attention deficit hyperactivity disorder. limited thereto . US 2017 /0304150 A1 Oct. 26 , 2017

EXAMPLES Example 5 Example 1 [0081 ] Dronabinol Capsules , 10 mg [0077 ] Dronabinol Capsules, 2 . 5 mg S . Name of Packaging Qty. / 36000 No. Component Unit units S . Name of Packaging Qty. / 36000 No . Component Unit units Dronabinol Capsules, 10 mg No 36000 . 00 Aquaba 200 - 114 mm (PVC Film ) Kgs 40 . 00 Dronabinol Capsules , 2 . 5 mg No 36000 .00 Kgs 40 .00 Aquaba 200 - 114 mm ( PVC Film ) Kgs 40 .00 CrisPak PL - 108 mm (PVC Film ) CrisPak PL - 108 mm ( PVC Film ) Kgs 40 .00 1 gram Sorb - it Canister No. 9000. 00 1 gram Sorb - it Canister No . 9000 . 00 Žlarinito Display Carton ( 8 .686 x 3 .625 x 4 . 4063 ) Nos 120 .00 Display Carton ( 8 .686 x 3 .625 x 4 . 4063 ) Nos 120 . 00 Display Carton Label for Nos 120 .00 Display Carton Label for Nos 120 . 00 200 / 225 cc Master Carton Nos 30 . 00 200 / 225 cc Master Carton Nos 30 . 00

Example 2 Example 6 [ 0078 ] Dronabinol Capsules, 2 .5 mg [0082 ] Dronabinol Capsules, 10 mg

S . Name of Packaging Qty. / 36000 S . Name of Packaging Qty. / 36000 No . Component Unit units No . Component Unit units Dronabinol Capsules , 2 . 5 mg No 36000 .00 Dronabinol Capsules , 10 mg No 36000 .00 Aquaba 200 - 114 mm ( PVC Film ) Kgs 40 .00 Aquaba 200 - 114 mm ( PVC Film ) Kgs 40 . 00 CrisPak PL - 108 mm ( PVC Film ) Kgs 40 . 00 CrisPak PL - 108 mm (PVC Film ) Kgs 40 . 00 2 gram Sorb - it Tyvek ( 22 x 53) No. 9000 . 00 2 gram Sorb - it Tyvek (22 x 53 ) No . 9000 . 00 Display Carton ( 8 .686 x 3 .625 x 4 .4063 ) Nos 120 .00 Display Carton ( 8 .686 x 3 .625 x 4 . 4063 ) Nos 120 . 00 Display Carton Label for Nos 120 .00 Display Carton Label for Nos 120 . 00 200 /225 cc Master Carton Nos 30 .00 200 /225 cc Master Carton Nos 30 . 00

Example 3 Example 7 [ 0079 ] Dronabinol Capsules, 2 . 5 mg [0083 ] Dronabinol Capsules , 10 mg

S . Name of Packaging Qty. / 36000 S . Name of Packaging Qty ./ 36000 No. Component Unit units No . Component Unit units Dronabinol Capsules , 2 . 5 mg No 36000 . 00 Dronabinol Capsules , 10 mg 36000 . 00 Aquaba 200 - 114 mm ( PVC Film ) Kgs 40 . 00 Aquaba 200 - 114 mm ( PVC Film ) Kgs 40 . 00 CrisPak PL - 108 mm ( PVC Film ) Kgs 40 . 00 CrisPak PL - 108 mm (PVC Film ) 40 . 00 StabilOX ® DF - 100 -H31 ( Tyvek ) No . 9000 . 00 StabilOX ® DF - 100 -H31 ( Tyvek ) No . 9000 . 00 Display Carton ( 8 .686 x 3 . 625 x 4 . 4063) Nos 120 .00 Display Carton ( 8 . 686 x 3 .625 x 4 .4063 ) Nos 120 . 00 Display Carton Label for Nos 120 . 00 Display Carton Label for Nos 120 . 00 200 /225 cc Master Carton Nos 30 . 00 Zlarinitron 200 /225 cc Master Carton Nos 30 .00 Example 4 Example 8 [0080 ] Dronabinol Capsules, 2 . 5 mg [0084 ] Dronabinol Capsules , 10 mg

S . Name of Packaging Qty ./ 36000 Name of Packaging Qty. / 36000 No . Component Unit units Component Unit units Dronabinol Capsules, 2 . 5 mg No 36000 .00 Dronabinol Capsules , 10 mg No 36000 . 00 Aquaba 200 - 114 mm (PVC Film ) Kgs 40 .00 Aquaba 200 - 114 mm (PVC Film ) Kgs 40 . 00 CrisPak PL - 108 mm (PVC Film ) Kgs 40 .00 Cris Pak PL - 108 mm ( PVC Film ) Kgs 40 . 00 StabilOX ® DF- 200 - H31 ( Tyvek ) No . 9000 . 00 StabilOX ® DF- 200 -H31 ( Tyvek ) No . 9000 . 00 nimifinos Display Carton ( 8 .686 x 3 .625 x 4 .4063 ) Nos 120 .00 Display Carton ( 8 .686 x 3 .625 x 4 . 4063 ) Nos 120 . 00 Display Carton Label for Nos 120 . 00 Display Carton Label for Nos 120 . 00 200 /225 cc Master Carton Nos 30 . 00 Žarimitivo 200 /225 cc Master Carton Nos 30 . 00 US 2017 /0304150 A1 Oct . 26 , 2017

Example 9 What is claimed is : 1 . A packaging system for a pharmaceutical product that [0085 ] Pravastatin Sodium Tablets , USP 20 mg is sensitive to oxygen and /or moisture comprising : a blister pack comprising : S . Name of Packaging Qty ./ 10000 ( i ) a blister sheet comprising of an array of intercon No. Component Unit units nected cavities connected through channels that Pravastatin Sodium Tablets , USP 20 mg No 10000 . 00 allows the exchange of air between them ; Aquaba 200 - 114 mm (PVC Film ) Kgs 15 .00 ( ii) wherein one or more of the cavities serve as a CrisPak PL - 108 mm ( PVC Film ) Kgs 15 . 00 reservoirs holding an oxygen scavenger and / or a 2 gram Sorb - it Canister No. 1000 . 00 desiccant at concentrations high enough to provide Display Carton ( 8 .686 x 3 .625 x 4 . 4063 ) Nos 100 .00 Display Carton Label for Nos 100 .00 higher equilibration time for oxygen and / or mois 200 /225 cc Master Carton Nos 20 . 00 ture ; IOWAW ( iii ) further wherein one or more of the cavities com prise at least one pharmaceutical product that is sensitive to oxygen and / or moisture ; and Example 10 ( iii ) a frangible lidding sealed to the sheet protecting [0086 ] Pravastatin Sodium Tablets , USP 20 mg the product in the cavity . 2 . The package in claim 1 , wherein the pharmaceutical product contains an active that comprises at least one amine S . Name of Packaging Qty ./ 10000 as a part of chemical groups. No. Component Unit units 3 . The package in claim 1 , where in the pharmaceutical Pravastatin Sodium Tablets , USP 20 mg No 10000 .00 products is an active that is selected from the group con Aquaba 200 - 114 mm ( PVC Film ) Kgs 15 .00 sisting of cannabinoids, drobinol, dronabinol , d - tetrahydro CrisPak PL - 108 mm (PVC Film ) Kgs 15 .00 cirimifino 3 gram Sorb - it Tyvek (22 x 53 ) No . 1000 . 00 cannabinol, cannabidiol, and combinations thereof . Display Carton ( 8 .686 x 3 .625 x 4 .4063 ) Nos 100 . 00 4 . The package in claim 1 , wherein the pharmaceutical Display Carton Label for Nos 100 .00 product is selected from the group consisting of statins , 200 / 225 cc Master Carton Nos 20 .00 lovastatin , simvastatin , fluvastatin , atorvastatin , pitavastatin , and combinations thereof. 5 . The package in claim 1 , wherein the pharmaceutical Example 11 product is selected from the group consisting of morphine , hydromorphone , promethazine , dopamine , epinephrine, nor [ 0087 ] Pravastatin Sodium Tablets , USP 20 mg epinephrine , esterified estrogen , ephedrine , pseudoephed rine , acetaminophen , ibuprofen , danofloxacin , erythromy cin , penicillin , cyclosporine , methyldopate , cetirizine , S . Name of Packaging Qty . / 10000 diltiazem , verapamil , mexiletine, chlorothiazide , carbam No. Component Unit units azepine, selegiline, oxybutynin , vitamin A , vitamin B , vita Pravastatin Sodium Tablets , USP 20 mg No 10000 .00 min C , L - , L -tryptophan , and combinations thereof. Aquaba 200 - 114 mm (PVC Film ) Kgs 15 .00 CrisPak PL - 108 mm (PVC Film ) Kgs 15 .00 6 . The package in claim 1 wherein the blister sheet that StabilOX ® DF - 200 - H31 ( Tyvek ) No . 1000 . 00 has light and moisture protectant properties . Display Carton ( 8 .686 x 3 .625 x 4 . 4063) Nos 100 . 00 7 . The package in claim 1 wherein the blister sheet is Display Carton Label for Nos 100 . 00 made of materials selected from the group consisting of 200 /225 cc Master Carton Nos 20 .00 polyvinylchloride, polyvinylidene chloride, polycarbonate , polyester, copolyester, acrylonitrile , low density polyethyl ene , polypropylene , and combinations thereof. Example 12 8 . The package in claim 1 wherein the oxygen scavenger is selected from the group consisting of organic , inorganic , [0088 ] Pravastatin Sodium Tablets , USP 20 mg metallic , non -metallic , and enzymatic in nature . 9 . The package in claim 1 , where in the desiccants is S. Name of Packaging Qty . / 10000 selected from the group consisting of organic desiccants , No . Component Unit units inorganic desiccants , uncoated polymers , coated adsorbent polymers , and combinations thereof. Pravastatin Sodium Tablets , USP 20 mg No 10000 .00 Aquaba 200 - 114 mm (PVC Film ) Kgs 15 .00 10 . The package in claim 1 wherein the frangible lidding CrisPak PL - 108 mm ( PVC Film ) Kgs 15 . 00 has moisture barrier properties . StabilOX ® DF - 300 - H31 ( Tyvek ) No . 1000 . 00 Display Carton ( 8 .686 x 3 .625 x 4 .4063 ) Nos 100 . 00 11 . A blister package for an oxygen and /or moisture Display Carton Label for Nos 100 .00 sensitive pharmaceutical product comprising : mirnos 200 /225 cc Master Carton Nos 20 . 00 ( i) a shaped film comprising : ( A ) a plurality of cavities configured to each hold a [0089 ] While the invention has been described in detail single unit dose of the pharmaceutical product , and and with reference to specific examples thereof, it will be ( B ) at least one airflow channel , and apparent to one skilled in the art that various changes and ( C ) at least one reservoir ; modifications can be made therein without departing from wherein the at least one airflow channel connects each of the spirit and scope thereof. the plurality of cavities to the at least one reservoir; US 2017 /0304150 A1 Oct. 26 , 2017 11

( ii ) a frangible lidding sealed to the shaped film so that the 14 . The package of claim 11 , wherein the cavities are unit dose is substantially confined between said fran - interconnected by airflow channels . gible lidding and said at least one cavity ; 15 . The package of claim 11 , wherein the pharmaceutical ( iii ) an absorbent confined between the reservoir and the product is selected from the group consisting ofmorphine , frangible lidding ; hydromorphone , promethazine , dopamine , epinephrine , nor (iii ) optionally a backing film ; and epinephrine , esterified estrogen , ephedrine , pseudoephed ( iv ) single unit doses of an oxygen and / or moisture rine, acetaminophen , ibuprofen , danofloxacin , erythromy sensitive pharmaceutical product confined between the cin , penicillin , cyclosporine , methyldopate , cetirizine , cavities and the frangible lidding . diltiazem , verapamil, mexiletine , chlorothiazide, carbam 12 . The package of claim 11, wherein the absorbent azepine, selegiline, oxybutynin , vitamin A , vitamin B , vita comprises a desiccant and an oxygen absorber , wherein the min C , L - cysteine, L - tryptophan , and combinations thereof. desiccant is selected from the group consisting of silica gel, 16 . The package of claim 11, wherein the shaped film clay desiccants , calcium sulfate , calcium chloride , calcium comprises polyvinyl chloride , polyvinylidene chloride , oxide, zeolite , activated alumina , activated charcoal, and polycarbonate , polyester, copolyester, acrylonitrile , low combinations thereof, and the oxygen absorber is selected density polyethylene , polypropylene , or a combination from the group consisting of iron oxidase , glucose oxidase , thereof. sodium sulfate , potassium chloride, ammonium chloride , 17 . The package of claim 11 , wherein an active pharma ammonium sulfate , calcium chloride , sodium phosphate , ceutical ingredient in the pharmaceutical product is an active calcium phosphate , magnesium chloride , and combinations that is selected from the group consisting of cannabinoids , thereof. drobinol, dronabinol, d - tetrahydrocannabinol, cannabidiol, 13 . The package of claim 12 , wherein the absorbent statins , lovastatin , simvastatin , fluvastatin , atorvastatin , comprises a moisture sensitive color indicator to indicate pitavastatinpita , and combinations thereof . when the desiccant is no longer operable . * * * * *