Patent Publication Number: US-2021161764-A1

Title: Pharmaceutical packs comprising holographic lidding material, and method of making the same

Description:
PRIORITY CLAIM AND CROSS-REFERENCE 
     This application is a continuation-in-part of U.S. application Ser. No. 15/792,248, filed Oct. 24, 2017, which claims the benefit of U.S. Provisional Application No. 62/413,253, filed Oct. 26, 2016, which applications are expressly incorporated by reference herein in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The disclosure relates to pharmaceutical product packaging generally. More particularly, the disclosed subject matter relates to a pharmaceutical pack such as a blister pack comprising anti-counterfeiting features, and the method of making the same. 
     BACKGROUND 
     Blister packs are commonly used for the distribution of pharmaceutical products such as pills or capsules because they provide excellent product protection, tamper evidence, childproof safeguards, as well as dosage compliance to show exactly the number of pills that have been taken and those that remain. 
     One extremely important issue that is currently not being adequately addressed by pharmaceutical blister pack manufacturers is product authentication. A counterfeit drug may contain inappropriate quantities or none of its active ingredients, may be improperly processed within the body, may contain ingredients that are not on the label (which may or may not be harmful), or may be supplied with inaccurate or fake packaging and labeling. The World Health Organization estimates that 10 percent of medicines globally—and as much as one-third in some developing countries—are likely to be counterfeit, and that the annual earnings from substandard and/or counterfeit drugs are over 75 billion U.S. dollars. 
     Currently, the counterfeiting of pharmaceutical products places the health of millions of patients at risk, who assume that the medications that they are buying are safe and effective. 
     SUMMARY OF THE INVENTION 
     The present disclosure provides a pharmaceutical pack such as a blister pack, and a method of making the same. 
     In some embodiments, such a pharmaceutical pack (e.g., a blister pack) comprises a blister layer and a lidding sheet disposed over the blister layer. The blister layer defines at least one opening. The lidding sheet comprises one or multiple layers, for example, a first layer and optionally a second layer. The first layer comprises at least one hologram, which might be embossed, transferred, or stamped on or in a base material of the first layer. The base material of the first layer may comprise metal, plastics, paper, or a combination thereof. The second layer is a plastic film or a metal foil (e.g. aluminum foil), or a combination thereof. The first layer is disposed on the second layer. The blister layer and the lidding sheet are sealed together and define at least one cavity for holding at least one pharmaceutical dosage form therein. 
     In some embodiments, the blister layer comprises a plastic material having an optical transparency to visible light in the range of from about 60% to about 100% (e.g., 80-100%, 90-100%). Examples of a suitable material for the blister layer include, but are not limited to, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polychlorotrifluoro ethylene (PCTFE), cyclic olefin copolymers (COC), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), and any combination thereof. 
     The at least one hologram in the lidding sheet may be disposed over the at least one cavity. The hologram may be overt in the pharmaceutical pack in some embodiments. In some embodiments, the hologram will be visible on the top surface of the pharmaceutical pack. The hologram may be designed to provide hidden 2-D or 3-D security features for authentication, and to prevent counterfeiting. In some embodiments, the first layer in the lidding sheet is a metallized holographic paper. The second layer in the lidding sheet may be a plastic (e.g., PET), a metal (e.g., aluminum or tin) foil, or any combination thereof (e.g., aluminum/PET). In some embodiments, for child-resistant blister packs, the second layer made of polyethylene terephthalate (PET) or other plastic film, which may be transparent, is used. In some embodiments, the second layer being an aluminum foil is used when the first layer is a holographic paper. 
     In some embodiments, the lidding sheet further comprises an adhesive disposed below the first layer, for example, below the second layer or on the bottom surface of the second layer. The blister layer and the lidding sheet are bonded together using the adhesive. 
     In some embodiments, the pharmaceutical pack further comprises an ink printed on the top surface of the first layer of the lidding sheet and surrounding the at least one hologram. The lidding sheet may further comprise a primer disposed on the top surface of the first layer and between the first layer and the ink. A heat resistant primer is preferred. The primer is used to improve printability of the lidding layer, and also improve adhesion between the ink and the lidding layer. The primer is also utilized to protect the hologram from the high levels of heat that are inherent in the blister-pack sealing process. The ink, which may be in white or a light color, can be used to cover and/or obscure any defects in a portion of hologram or the surrounding area. Possible damage to the holograms outside of the recessed capsule area may be caused by the heat sealing process due to the high sensitivity of embossed holograms to heat. Consumer information such as words, logo, graphics, drug name, manufacturing, expiration dates, dosing instructions, and/or warning information may be printed on the ink. 
     In some embodiments, the pharmaceutical pack includes multiple (e.g., 2-8) sealed cavities defined by the blister layer and the lidding sheet. One or more (e.g., two) pills or tablets are disposed in each cavity. The pharmaceutical pack may be a blister pack, which may be one of three types: a push-through type, peel-push type, or a lock type. For example, in some embodiments, the pharmaceutical pack is a push-through type of blister pack. A consumer can use a finger to push against the blister layer at or above a cavity to break the lidding layer to push the pharmaceutical dosage out of the cavity. In some other embodiments, the blister layer may be peeled away from the lidding material so that a consumer can retrieve the pharmaceutical dosage that is sealed in a cavity. 
     In another aspect, the present disclosure provides a method for making a pharmaceutical pack such as a blister pack as described. In some embodiments, such a method comprises the following steps. A lidding sheet comprising a first layer and optionally a second layer is provided. The first layer comprises at least one hologram and is disposed on the second layer. The second layer is a plastic (e.g., PET) film, a metal (e.g., Al) foil, or a combination thereof (e.g., laminated PET/Al). The method further comprises providing a blister layer defining at least one opening, placing the lidding sheet over the blister layer, and applying a plate (e.g., a heating plate) defining a recess or a through-hole therein onto the lidding sheet. At least one pharmaceutical dosage form is introduced into the at least one opening defined by the blister layer. The recess or the through-hole in the plate is disposed above the at least one hologram. The plate may not be in direct contact with the at least one hologram in some embodiments, or at least not in direct contact with the main body of the at least one hologram, which is designed to remain in a final product. The at least one hologram above the at least one opening of the blister layer does not directly contact with the plate during the step of sealing. The plate may be made of metal, ceramic, or other suitable material, and may function as a molding plate. The plate may be used as a sealing tool or a portion of a sealing tool, and is configured to prevent or minimize any damage to the at least one hologram, because of the sensitivity of holograms to heat. 
     The method further comprises sealing the lidding sheet and the blister layer together so as to form a pharmaceutical pack. The blister layer and the lidding sheet define at least one cavity for holding at least one pharmaceutical dosage form therein. 
     In some embodiments, the step of providing the lidding sheet comprises any of the following steps: bonding the first layer and the second layer together, applying an adhesive below the first layer, for example, below the second layer or onto the bottom surface of the second layer, and applying a primer onto a top surface of the first layer. In some embodiments, the adhesive is a heat activated adhesive, and the lidding sheet and the blister layer are sealed together using heating and pressure. In some other embodiments, the adhesive may be a pressure sensitive adhesive, and the lidding sheet and the blister layer are sealed together using pressure without heat. 
     In some embodiments, the method further comprises printing an ink on the top surface of the first layer of the lidding sheet. The ink is printed in such a manner that the hologram above the cavity is left uncovered by the ink and remains clearly visible to the consumer. The hologram above the cavity is not be negatively impacted by the heat due to the recess or through-hole in the heating plate that has been designed to be directly above the cavity for pills or tablets. The remainder of the holographic material, which is negatively impacted by its direct contact with the heating plate is covered by ink to obscure the holographic distortion created by heat. This allows this area to be overprinted with a white, or light colored layer of ink, which can then be printed with marketing or dosage information. In some embodiments, the ink is applied to the areas surrounding the at least one hologram, which is visible in a final product. 
     In some embodiments, the at least one hologram in the lidding sheet is placed over the at least one opening (or cavity) defined by the blister layer. The hologram is intended to be visible on the top surface of the pharmaceutical pack in some embodiments. 
     In some embodiments, the present disclosure provides a method for forming a blister pack. Such a method comprises providing a lidding sheet comprising a first layer and optionally a second layer. The first layer comprises at least one hologram and is disposed on the second layer. The second layer is a plastic film, or a metal foil, or any combination thereof. For example, the second layer may include two layers: a PET layer and an aluminum layer. In some embodiments, providing the lidding sheet comprises the following steps: bonding the first layer and the second layer (including possibly multiple layers for the second layer), applying an adhesive onto a bottom surface of the second layer, and applying a heating resist primer onto a top surface of the first layer. 
     The method further comprises placing the lidding sheet over a blister layer. The blister layer defines at least one opening. The at least one hologram is disposed over the at least one opening. The method further comprises applying a plate defining a recess or through-hole therein above and/or onto the lidding sheet. The plate is for heat and pressure sealing. The recess or the through-hole is disposed above the at least one hologram. The method further comprises sealing the lidding sheet and the blister layer together utilizing heat and pressure. The blister layer and the lidding sheet define at least one cavity for holding at least one pharmaceutical dosage form therein. The method may further comprise printing a white ink on the top surface of the first layer of the lidding sheet so that the white ink surrounds the at least one hologram, after the lidding sheet and the blister layer are sealed together. Information such as a drug&#39;s name, manufacturing and expiration dates, dosing instructions, and warning information may be then printed on the white ink. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure is best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, according to common practice, the various features of the drawings are not necessarily to scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. 
       Like reference numerals denote like features throughout the specification and drawings. 
         FIG. 1A  is a flow chart illustrating an exemplary method for forming a pharmaceutical pack in accordance with some embodiments. 
         FIG. 1B  is a flow chart illustrating an exemplary method for providing a lidding sheet in accordance with some embodiments. 
         FIG. 2A  is a perspective view of an exemplary first layer of a lidding sheet comprising at least one hologram in accordance with some embodiments. 
         FIG. 2B  is a cross-sectional view of the exemplary first layer of  FIG. 2A  (along line A-A′). 
         FIG. 3A  is a perspective view of an exemplary lidding sheet comprising at least one hologram in accordance with some embodiments. 
         FIG. 3B  is a cross-sectional view of the exemplary lidding sheet of  FIG. 3A  (along line B-B′). 
         FIG. 4  is a cross-sectional view of an exemplary blister layer defining at least one opening in accordance with some embodiments. 
         FIG. 5A  is a perspective view of an exemplary plate (or sealing tool) defining at least one recess in accordance with some embodiments. 
         FIG. 5B  is a cross-sectional view of the exemplary plate (or sealing tool) of  FIG. 5A  (along line C-C′). 
         FIG. 6  is a cross-sectional view of a portion of an exemplary assembly during fabrication comprising a blister layer, a lidding sheet, and a plate in accordance with some embodiments. 
         FIG. 7  is a cross-sectional view of an exemplary pharmaceutical pack in accordance with some embodiments. 
         FIG. 8A  is a plan view illustrating an exemplary front side (the lidding sheet side) of an exemplary pharmaceutical pack in accordance with some embodiments. 
         FIG. 8B  is a plan view illustrating an exemplary back side (the blister layer side) of the exemplary pharmaceutical pack of  FIG. 8A . 
       Similar to  FIG. 5B ,  FIG. 9  is a cross-sectional view of another exemplary plate (or sealing tool) of  FIG. 5A  (along line C-C′) having at least one through-hole in accordance with some embodiments. 
       Similar to  FIG. 6 ,  FIG. 10  is a cross-sectional view of a portion of an exemplary assembly during fabrication comprising a blister layer, a lidding sheet, and a plate of  FIG. 5B  in accordance with some embodiments. 
         FIG. 11A  is a perspective view of an exemplary plate (or sealing tool) defining at least one through-hole in accordance with some embodiments. 
         FIG. 11B  is a cross-sectional view of the exemplary plate (or sealing tool) of  FIG. 11A  (along line C-C′). 
         FIG. 12  is a cross-sectional view of a portion of an exemplary assembly during fabrication comprising a blister layer, a lidding sheet, and a plate of  FIGS. 11A-B  in accordance with some embodiments. 
     
    
    
     DETAILED DESCRIPTION 
     This description of the exemplary embodiments is intended to be read in connection with the accompanying drawings, which are to be considered part of the entire written description. In the description, relative terms such as “lower,” “upper,” “horizontal,” “vertical,”, “above,” “below,” “up,” “down,” “top” and “bottom” as well as derivative thereof (e.g., “horizontally,” “downwardly,” “upwardly,” etc.) should be construed to refer to the orientation as then described or as shown in the drawing under discussion. These relative terms are for convenience of description and do not require that the apparatus be constructed or operated in a particular orientation. Terms concerning attachments, coupling and the like, such as “connected” and “interconnected,” refer to a relationship wherein structures are secured or attached to one another either directly or indirectly through intervening structures, as well as both movable or rigid attachments or relationships, unless expressly described otherwise. 
     For purposes of the description hereinafter, it is to be understood that the embodiments described below may assume alternative variations and embodiments. It is also to be understood that the specific articles, compositions, and/or processes described herein are exemplary and should not be considered as limiting. 
     In the present disclosure the singular forms “a,” “an,” and “the” include the plural reference, and reference to a particular numerical value includes at least that particular value, unless the context clearly indicates otherwise. Thus, for example, a reference to “a hologram” or “a holographic structure” is a reference to one or more of such structures and equivalents thereof known to those skilled in the art, and so forth. When values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. As used herein, “about X” (where X is a numerical value) preferably refers to ±10% of the recited value, inclusive. For example, the phrase “about 8” preferably refers to a value of 7.2 to 8.8, inclusive; as another example, the phrase “about 8%” preferably (but not always) refers to a value of 7.2% to 8.8%, inclusive. Where present, all ranges are inclusive and combinable. For example, when a range of “1 to 5” is recited, the recited range should be construed as including ranges “1 to 4”, “1 to 3”, “1-2”, “1-2 &amp; 4-5”, “1-3 &amp; 5”, “2-5”, and the like. In addition, when a list of alternatives is positively provided, such listing can be interpreted to mean that any of the alternatives may be excluded, e.g., by a negative limitation in the claims. For example, when a range of “1 to 5” is recited, the recited range may be construed as including situations whereby any of 1, 2, 3, 4, or 5 are negatively excluded; thus, a recitation of “1 to 5” may be construed as “1 and 3-5, but not 2”, or simply “wherein 2 is not included.” It is intended that any component, element, attribute, or step that is positively recited herein may be explicitly excluded in the claims, whether such components, elements, attributes, or steps are listed as alternatives or whether they are recited in isolation. 
     The present disclosure provides a pharmaceutical pack (or package) such as a blister pack, and a method of making the same. The pharmaceutical pack comprises at least one hologram to provide authentication and prevent counterfeiting. A holographic lidding material layer is used in some embodiments. 
     In  FIGS. 1A-8B , like items are indicated by like reference numerals, and for brevity, descriptions of the structure, provided above with reference to the preceding figures, are not repeated. The methods described in  FIGS. 1A-1B  are described with reference to the exemplary structure described in  FIGS. 2A-6 . The resulting product structures are illustrated in  FIGS. 7 and 8A-8B . 
     Unless expressly indicated otherwise, references to “hologram” or “holographic feature” made below will be understood to encompass a photograph of an interference pattern that, when illuminated, produces a two-dimensional or three-dimensional image. 
     References to “a blister layer” or “a blister film” made below will be understood to encompass a layer used as a bottom part of a pharmaceutical pack such as a blister pack, with one or more recesses or openings formed therein. Such recesses or opening are formed through vacuum forming or pressure forming. A product piece such as a pharmaceutical dosage form (e.g., a tablet or pill) is positioned and held therein. 
     References to “a lidding sheet,” “lidding foil,” or “a lidding material layer” made below will be understood to encompass a cover of a pharmaceutical pack such as a blister pack, and such a cover is placed over and sealed to the blister layer. The one or more recesses or openings in a blister layer are sealed by a lidding sheet to form one or more corresponding cavities. At least one pharmaceutical dosage form (e.g., a tablet or pill) is disposed and held therein in a pharmaceutical pack. For brevity, an adhesive and a primer disposed thereon are also described as portions of a lidding sheet in the present disclosure. The adhesive and the primer can be described as separate layers or materials. 
     A lidding material layer is the structural component upon which a blister package is built. Such a lidding material layer may be made of metal such as aluminum, paper, or plastic or any layered combination thereof. The lidding material layer is adhered to a blister layer (e.g., a plastic layer) with the use of heat and/or pressure, through a heat or pressure sensitive adhesive coating. 
     To identify counterfeit packaging, the authenticity of a blister pack comprising pharmaceutical products can be visually confirmed with the use of custom overprinted holographic lidding material that is embossed, transferred or stamped into layered sheets of paper, plastic, and/or aluminum. Lidding material can be holographically embossed using images such as a pharmaceutical company&#39;s logo combined with a wide range of proprietary 2D or 3D images specifically designed to deter counterfeiting. The holographic images can then be selectively overprinted with graphics along with the product&#39;s applicable dosing/usage information. 
     To maximize the security and performance of the holographic lidding material layer additional overt and covert elements can be integrated into the holograms. The use of security devices such as hidden (latent) images, which can only be detected with special lighting (such as laser or UV), or the integration of micro text into the holographic image, can make the fraudulent duplication the holographic substrate extremely difficult to implement. In addition to use within the pharmaceutical industry, other valuable consumer goods marketed in blister packs that may be subject to fraudulent duplication (i.e. branded disc shaped batteries) can also benefit from the use of holographic lidding material for product authentication. 
     The method and the product provided in the present disclosure are suitable for mass production of blister pack packaging having holograms, which was previously considered to be cost prohibitive. Wide-web holographic manufacturing has reduced the cost of producing large quantities of holograms so that they can now be cost-effectively used with disposable packaging applications. In accordance with some embodiments, a holographic material layer can be used as a lidding sheet or as a layer for the lidding sheet. Holograms that are more complex can be cost-effectively included to provide pharmaceutical packs with heightened security features. In addition to its functional improvements, the resulting product projects a high quality aesthetic appearance. 
     Referring to  FIGS. 1A-1B , an exemplary method  10  for making a pharmaceutical pack such as a blister pack is provided. In some embodiments, such a method comprises one or more of steps  12 ,  20 ,  30 ,  40  and  50 . 
     At step  12 , a lidding sheet  110  incorporating at least one hologram is provided. In some embodiments, the lidding sheet  110  comprises a first layer  102  and a second layer  112 . The second layer  112  may be optional in some embodiments. An exemplary first layer  102  is illustrated in  FIGS. 2A-2B . An exemplary lidding sheet  110  is illustrated in  FIGS. 3A-3B . 
     Referring to  FIGS. 2A-2B , the first layer  102  comprises at least one hologram  106 . The first layer  102  is disposed on the second layer  112 . The second layer  112  may be optional in some embodiments. 
     The at least one hologram  106  may be transferred onto, embossed directly onto, or hot or cold stamped onto the first layer  102 , which includes a base material  104 . The base material  104  may be paper, plastic, aluminum, or a combination thereof. The at least one hologram  106  is transferred, embossed, stamped onto or into the base material  104 . In another word, the first layer  102  includes a base material  104  and the at least one hologram  106 . 
     In some embodiments, the first layer  102  in the lidding sheet  110  is a metallized holographic paper. For example, a transfer holographic aluminum foil is used in some embodiments. The holographic security effect has been transferred on the aluminum surface from a PET film (or carrier material). In some other embodiments, a directly embossed holographic foil or paper is used. For example, a holographic aluminum foil (HOLO-A), which is directly embossed, is available under a trademark ALUCARE®, from Daivy s. r. l. of Italy. The holographic images are micro-embossed on the foil before the packing process. The holographic images may be in a thickness from 7 microns to 60 microns. The directly embossed holographic aluminum foil may be used for “push-through” pharmaceutical blister packs. When the directly embossed holographic aluminum foil is used as the first layer  102 , the second layer  112  may be optional for “push-through” blister packaging applications. 
     In some embodiments, the first layer  102  is a holographic paper. The holographic paper can be available from a company such as the Hazen Paper Company of Massachusetts, U.S.A. The holographic paper may have a weight in the range of from about 10 g/m 2  to about 50 g/m 2 , for example from about 15 g/m 2  to about 30 g/m 2 . 
     Referring to  FIGS. 2A-2B , in some embodiments, the at least one hologram  106  may be patterned on the first layer  102 . The holograms  106  may be also distributed throughout the first layer  102  including peripheral areas  108  ( FIG. 2A ). The excessive holograms in such peripheral areas  108  or any other area are to be covered by inks in a step of printing (i.e. overprinting) as described below. 
     The second layer  112  in the lidding sheet  110  may be a plastic (e.g., PET), a metal (e.g., aluminum or tin) foil, or any combination thereof (e.g., aluminum/PET). In some embodiments, the second layer  112  made of polyethylene terephthalate (PET) or other plastic film, which may be transparent, is used. Such a combination may be used for child resistant blister packs. In some embodiments, the second layer  112  being an aluminum foil is used when the first layer  102  is a holographic paper. For child resistant packs, an additional layer of PET can be used in combination with an aluminum foil as the second layer  112  when a holographic paper is used as the first layer  102 . 
     The selection and combination of the first layer  102  and the second layer  112  can provide different structures. For illustration only, the following exemplary structures can be obtained. In some embodiments, the first layer  102  includes a base material  104  made of metal (e.g., aluminum) and the at least one hologram  106 . The first layer  102  without a second layer  112  is used in the lidding sheet  110  for push-though packs. 
     In some embodiments, the first layer  102  includes a base material  104  made of metal (e.g., aluminum) and the at least one hologram  106 . The first layer  102 , and a second layer  112  such as a PET film are used in the lidding sheet  110  for child-resistant packs. 
     In some embodiments, the first layer  102  includes a base material  104  made of paper and the at least one hologram  106 . A second layer  112  being an aluminum foil is used in the lidding sheet  110  for improved moisture resistance. 
     In some embodiments, the first layer  102  is a holographic paper as described. A second layer  112  including a PET film and an aluminum foil is used in the lidding sheet  110  for child-resistant packs having improved moisture resistance. The PET film can be disposed between the first layer  102  and the aluminum foil. 
     Referring to  FIG. 1B , in some embodiments, an exemplary step  12  of providing the lidding sheet  110  may comprise any or all of steps  14 ,  16  and  18 . The resulting structure of the lidding sheet  110  is illustrated in  FIGS. 3A-3B . 
     At step  14 , the first layer  102  and the second layer  112  are bonded together. In some embodiments, the first layer  102  and the second layer  112  are laminated together through a suitable process such as thermoforming. 
     At step  16 , an adhesive  114  is applied below the first layer  102 , for example, below the second layer  112  or onto a bottom surface of the second layer  112 . The adhesive  114  may be a heat activated adhesive, or a pressure sensitive adhesive. In some embodiments, the adhesive  114  may be cured using visible light or ultra-violet light. The adhesive  114  may be an oligomer or a polymer made of acrylic, acrylate, epoxy, urethane, silicone, or any combination thereof. 
     At step  18 , a primer  116  is applied onto a top surface of the first layer  102 . The primer  116  functions as an adhesion promoter for an ink to be subsequently printed thereon. Chemically, the primer  116  may comprise acrylic, epoxy, or silane coupling agents. The structure of  FIGS. 3A-3B  is for illustration only. In some embodiments, as a thin layer, the primer  116  is uniformly distributed on the entire top surface of the first layer  102 . In some embodiments, the primer  116  may be applied to the peripheral areas  108  only. The primer  116  is optically clear and resistant to heat in some embodiments. 
     At step  20  of  FIG. 1A , the lidding sheet  110  is placed over a blister layer  120 . Before step  20 , the blister layer  120  is provided. Referring to  FIG. 4 , an exemplary blister layer  120  is illustrated. Such an exemplary blister layer  120  includes a base film  122  having at least one recess, and defines at least one opening  134  therein. The exemplary blister layer  120  may be formed by depressing the base film  122  in a mold under pressure or under vacuum. 
     In some embodiments, the blister layer  120  comprises a plastic material having an optical transparency to visible light in the range of from about 60% to about 100% (e.g., 80-100%, 90-100%). The blister layer  120  may be transparent or translucent, and may have moisture barrier properties. In some embodiments, the blister layer  120  may be opaque. Examples of a suitable material for the blister layer  120  include, but are not limited to, polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polychlorotrifluoro ethylene (PCTFE), cyclic olefin copolymers (COC), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), and any combination thereof. 
     In some embodiments, the at least one hologram  106  is disposed over the at least one opening  124 . In some embodiments, at least one pharmaceutical dosage form  126  ( FIG. 6 ) is introduced into the at least one opening  124  defined by the blister layer  120 . 
     In some embodiments, the first layer  102  and the second layer  112  may be supplied or made in wide web sizes, resulting from web (roll) manufacturing processes. Before step  20  or  30 , they may be sliced into smaller rolls (e.g., about 140 mm in width), which will fit into blister packing machines. 
     At step  30 , a plate  130  defining a recess  134  therein is applied onto the lidding sheet  110 . An exemplary plate  130  (or called the upper sealing tool) is illustrated in  FIGS. 5A-5B . The resulting structure  140  at step  30  is illustrated in  FIG. 6 . 
     Referring to  FIGS. 5A-5B , an exemplary plate  130  may be made of a metal or ceramic, and defines at least one recess  134  therein on one surface  135 . The surface  135  may be referred as a bottom surface of the plate  130 . The plate  130  in  FIGS. 5A-5B  is placed upside down. The at least one recess  134  may have a suitable depth, for example, in a range from about 1 mm to 5 mm, and may have a shape matching with the opening  124  on the second layer  112 . At step  30 , the surface  135  is in contact with the first layer  102  of the lidding sheet  110 . The size and location of the at least one recess  134  correspond to the size and location of the at least one hologram  106  in the first layer  102 . For example, the size of one respective recess  134  on the plate  130  is substantially equal to or slightly larger than that of the size of a respective hologram  106 . 
     As illustrated in  FIG. 5A , the exposed surface  136  of the plate  130 , which is the surface  135  except the at least one opening  134 , corresponds to the peripheral areas  108  of the first layer  102  of the lidding sheet  110 . The exposed surface  136  includes a fine knurl pattern, with a plurality of a small projecting ridges, which will imprint such a pattern onto the lidding sheet  110  and the blister layer  120  when the two layers are sealed together. The use of the fine knurl pattern also allows for even heat distribution and minimizes the likelihood that the print primer on the holographic lidding material may adhere to the upper sealing tool. The knurl pattern shown in  FIG. 5A  is for illustration only. The whole exposed surface  136  may have such a knurl pattern, which is uniformly distributed thereon. The plate  130  may be made of metal, ceramic, or other suitable material, and may function as a molding plate. 
     Referring to  FIG. 6 , in some embodiments, the at least one recess  134  is disposed above the at least one hologram  106  in the lidding sheet  110 . The surface  136  of the plate  130  may not be in direct contact with the at least one hologram  106  in some embodiments, or at least not in direct contact with the main body of the at least one hologram  106 , which is shown in a final product. The hologram  106  may be sensitive to heat, mechanical stress, or other processing conditions. The plate  130  may be used as a sealing tool or a portion of a sealing tool, and is configured to prevent or minimize any damage to the at least one hologram  106 . Such a configuration in the plate  130  also minimizes damage to the pharmaceutical dosage  126  disposed in the recess  124  of the blister layer  120 . 
     At step  40  of  FIG. 1A , the lidding sheet  110  and the blister layer  120  are bonded and sealed together so as to form an exemplary pharmaceutical pack  150 . The resulting structure is illustrated in  FIG. 7 . The exemplary pharmaceutical pack  150  is also illustrated in  FIGS. 8A-8B . For the illustration only,  FIG. 7  shows only one unit of pharmaceutical pack, and  FIGS. 8A-8B  illustrates six units of pharmaceutical pack. For brevity, some features are illustrated or marked in only one unit, while the other units comprise the same features. An exemplary pharmaceutical pack  150  may comprise any number of units. The dotted line illustrates that each unit may be cut or torn from other units in one same pack. 
     The blister layer  120  and the lidding sheet  110  define at least one corresponding cavity  144  (or pocket) for holding at least one pharmaceutical dosage form  126  therein. In some embodiments, the adhesive  114  is a heat activated adhesive, and the lidding sheet  110  and the blister layer  120  are sealed together using heat and pressure by the plate  130 . Step  40  may be performed at an increased temperature, for example, in a range of from 150° C. to 250° C. (e.g., from 180° C. to 250° C.). The pressure may be in a range from about 1 Kg/cm 2  to about 10 Kg/cm 2  (e.g., about 2.8 Kg/cm 2  to about 5.6 Kg/cm 2 ). The dwell time may be in a range from about 0.01 second to about 1 second (e.g., from about 0.05 second to 0.25 second). In some other embodiments, the adhesive  114  is a pressure sensitive adhesive, and the lidding sheet  110  and the blister layer  120  are sealed together under pressure. The pressure and the dwell time may be the same as those described above. 
     As illustrated in  FIGS. 6-7 , in some embodiments, the at least one hologram  106  in the lidding sheet  110  is placed over the at least one opening  124  defined by the blister layer  120 . The hologram  106  will be visible on the top surface of the pharmaceutical pack. 
     At step  50  of  FIG. 1A , a continuous layer of opaque masking ink  152  ( FIG. 8A ) is printed on a top surface of the first layer  102  of the lidding sheet  110  and surrounding the at least one hologram  106 . Step  50  may be optional in some embodiments. This step is also referred as overprinting. The ink  152  may be printed in the peripheral areas  108 . In some embodiments, the ink  152  is white or in a light color. Step  50  may be performed after the lidding sheet  110  and the blister layer  120  are sealed together. Information  154  such as the drug&#39;s name, manufacturing date, expiration date, dosing instructions, and warning information may be then printed on the ink  152 . The ink  152  may also be used to cover possible distortions to the hologram  106 . 
     In some embodiments, the present disclosure provides solutions to at least two problems. One aspect being addressed relates to the degradation of holography by heat applies to the heating plates that are used to activate the adhesive layer of the lidding material thereby allowing it to adhere to the plastic “blister” material. In some embodiments, the heating plates are flat (without recess), and provide even distribution of heat across the entire surface of the lidding material. To prevent the heat from the plates from degrading the holography in specific areas, the plate used to apply the holographic lidding material is configured to have areas that are recessed in the positions that lie above where the pharmaceutical pills are inserted. This area does not require a heat seal (because it is directly above the pills). By recessing the heating plates in these areas, it will minimize the direct impact of the heat upon these areas, thus resulting in the elimination of the heat degradation of the holography in the locations above the pill cavities. 
     Another aspect being addressed is the impact of the blister-pack heat seal process with holograms  106 . To date, the heat used in the sealing process has prevented holography and a holography film from being used for the blister packaging application. Because embossed holograms are heat sensitive (heat tends to distort and degrade the holographic effect), the specific areas of the hologram that would be impacted by the heat sealing process will be overprinted with ink (e.g., an opaque white or light colored ink). The ink  152  can cover any holographic distortion, while allowing overprinting of the hologram with graphics and information such as dosage instructions. This overprinting is accomplished following the application of a primer  116  that is applied on top of the holographic material. 
     The combination of reduced heat in specified locations (e.g., above the cavity  144 ), and the use of an overprinted masking layer in areas where the heat is directly applied, allows the holography to remain visible without being degraded in the desired areas, for example, directly above the pill cavities. Such a combination also allows overprinting throughout the remainder of the lidding material so as to totally cover and obscure any distortion of the holographic images that would have been caused by the application of heat. The net result is unobscured and highly visible holographic images in the areas delineated by the cavity  144  surrounded by overprinted holography across the remaining surface area of the lidding material. The white masking overprinted area not only obscures the heat damaged/distorted holography, but also allows the surface to be utilized to print usage or dosage information that is typically used on the back of lidding material. 
     Referring to  FIG. 7 , and  FIGS. 8A-8B , the exemplary pharmaceutical pack  150  comprises a lidding sheet  110  and a blister layer  120 . The lidding sheet  110  is disposed over the blister layer  120 . The blister layer  120  defines at least one opening  124 . The lidding sheet  110  comprises a first layer  102  and optionally a second layer  112 . The first layer  102  comprises at least one hologram  106 . In some embodiments, the second layer  112  is a plastic film, a metal foil, or any combination thereof as described above. The first layer  102  is disposed on the second layer  112 . The blister layer  120  and the lidding sheet  110  are sealed together and define at least one cavity  144  for holding at least one pharmaceutical dosage  126  form therein. 
     The at least one hologram  106  in the lidding sheet  110  may be disposed over the at least one cavity  144 . The hologram  106  is visible on the top surface of the pharmaceutical pack  150 . In some embodiments, the hologram  106  may be made visible inside the at least one cavity  144  though the blister layer  120 . The hologram  106  may be designed to provide hidden 2-D or 3-D security features, and prevent from counterfeiting. 
     In some embodiments, the lidding sheet  110  further comprises an adhesive  114  disposed below the first layer  102 , for example, on a bottom surface of the second layer  112 . The blister layer  120  and the lidding sheet  110  are bonded together through the adhesive  114 . 
     In some embodiments, the exemplary pharmaceutical pack  150  further comprises an ink  152  printed on a top surface of the first layer  102  of the lidding sheet  110  and surrounding the at least one hologram  106 . The lidding sheet  110  may further comprise a primer  116  disposed on the top surface of the first layer  102  and between the first layer  102  and the ink  152 . The primer  116  is used to improve printability of the lidding layer  110 , improve adhesion between the ink  152  and the lidding layer  110 , and provide an additional protection to the holographic image from the heat inherent in the sealing process. The opaque ink  152 , which may be in white or a light color, can be used to cover any defects in a portion of hologram or the surrounding area. Information such as drug name, manufacturing and expiration dates, dosing instructions, and warning information may be printed on the surface of this masking layer of the ink  152 . Referring to  FIG. 8B , in the exemplary pharmaceutical pack  150  (or package), the laminated portion of the lidding sheet  110  and the blister layer  120  include a pattern  156 , which results from a fine knurl pattern  136  on the plate  130 . Such a pattern  156  may be more apparent on the bottom surface of the lidding sheet  110  in some embodiments. 
     In some embodiments, the exemplary pharmaceutical pack  150  includes multiple (e.g., 2-8) sealed cavities  144  defined by the blister layer  120  and the lidding sheet  110 . One or more (e.g., two) pills or tablets  126  are disposed in each cavity  144 . The exemplary pharmaceutical pack  150  provided in the present disclosure may be one of three different types of blister packs, depending on how a consumer or patient is meant to retrieve the pharmaceutical dosage form: push-through type, peel-push type and lock type. For example, in some embodiments, the pharmaceutical pack  150  is a push-through type of blister pack. A consumer can use his or her finger to push against the deformable blister layer  120  at the location of a cavity  144  to break the lidding layer  110  so as to push the pharmaceutical dosage  126  form out of the cavity  144 . In some other embodiments, a consumer first peels away the blister layer  120  (or at least the first layer  102 ) from the lidding material  110  so that a consumer can retrieve the pharmaceutical dosage  126  form sealed in a cavity  144 . If the first layer  102  is peeled away, the consumer may need to then push against the blister layer  120  at the location of a cavity  144  to break through the second layer  112  of the lidding sheet  110  and then retrieve a pharmaceutical dosage form. In the “lock” type of blister pack, a consumer can only access to the pharmaceutical dosage  126  form by cutting the lidding sheet  110  using a tool such as a pair of scissors, a knife, or with his or her nails. 
     Currently, the counterfeiting of pharmaceutical products places the health of millions of patients at risk who assume that the medications that they are buying are safe and effective. As a result of the innovations detailed in this patent application, the integration of holographic lidding material or film onto blister packages can now be used to provide an additional layer of security that will ensure that the pharmaceutical products that they contain are authentic. 
     In accordance with some embodiments, the exemplary plate  130  (or sealing tool) defines at least one through-hole  234  other than a recess  134 . In another word, each recess  134  described above becomes a hole  234  going through the plate  130 . Similar to  FIG. 5B ,  FIG. 9  illustrates another exemplary plate of  FIG. 5A  (along line C-C′) in accordance with some embodiments, except that the recesses  134  in  FIG. 5A  is replaced with through-holes  234 . Similar to  FIG. 6 ,  FIG. 10  illustrates a portion of an exemplary assembly during fabrication comprising a blister layer, a lidding sheet, and a plate in accordance with some embodiments. Unless expressly indicated otherwise, the descriptions of other components are also applicable to the structure of the plate  130  and the molding method using such a plate  130 . 
     At step  30  of  FIG. 1A , a plate  130  defining at least one through-hole  234  therein as illustrated in  FIG. 9  is applied onto the lidding sheet  110 . The resulting structure  140  at step  30  is illustrated in  FIG. 10 . 
     Referring to  FIG. 9 , an exemplary plate  130  defines at least one through hole  234 , which going through the plate  130  from one surface  135  to the opposing surface  137 . The surfaces  135  and  137  may be referred as a bottom surface and an upper surface of the plate  130 , respectively. The plate  130  may have side surfaces  132 . The plate  130  in  FIG. 9  is placed upside down. The at least one through hole  234  may have suitable sizes. The size and location of the at least holes  234  correspond to the size and location of the at least one hologram  106  in the first layer  102 . At step  30 , the surface  135  is in contact with the first layer  102  of the lidding sheet  110 . For example, the size of each respective hole  34  on the bottom surface  135  of the plate  130  is substantially equal to or slightly larger than that of the size of a respective hologram  106 . 
     The perspective view of the plate  130  illustrated in  FIG. 9  is similar to what is illustrated in  FIG. 5A , except that the recesses  134  in  FIG. 5A  is replaced with through-holes  234 . The exposed surface  136  of the plate  130 , which is the surface  135  except the at least one through-hole  234 , corresponds to the peripheral areas  108  of the first layer  102  of the lidding sheet  110 . The exposed surface  136  includes a fine knurl pattern as described in  FIG. 5A . 
     Referring to  FIG. 10 , in some embodiments, the at least one through-hole  234  is disposed above the at least one hologram  106  in the lidding sheet  110 . The surface  136  of the plate  130  may not be in direct contact with the at least one hologram  106  in some embodiments, or at least not in direct contact with the main body of the at least one hologram  106 , which is shown in a final product. The hologram  106  may be sensitive to heat, mechanical stress, or other processing conditions. The plate  130  may be used as a sealing tool or a portion of a sealing tool, and is configured to prevent or minimize any damage to the at least one hologram  106 . Such a configuration in the plate  130  also minimizes damage to the pharmaceutical dosage  126  disposed in the recess  124  of the blister layer  120 . Compared to the at least one recess  134  in the plate  130 , the through-holes  234  provides more heat dissipation, thus more protection to the hologram  106 . 
     The at least one through hole  234  may have any suitable configuration and sizes.  FIGS. 11A-B  illustrates an exemplary plate (or sealing tool) defining at least one through-holes  234  having opening size gradually increasing from one side to the opposing side in accordance with some embodiments.  FIG. 11A  is a perspective view, while  FIG. 11B  is a cross-sectional view.  FIG. 12  illustrates a portion of an exemplary assembly during fabrication comprising a blister layer, a lidding sheet, and the plate of  FIGS. 11A-B  in accordance with some embodiments. The at least one through-hole  234  is the same as that described above in  FIG. 9-10 , except that at least one through-holes  234  have an opening size gradually increasing from one side (surface  135 ) to the opposing side (surface  137 ) in accordance with some embodiments. 
     The cross-section of the through-hole  234  is in rectangular or square shape as illustrated in  FIGS. 11-12 . This shape is for illustration only. The cross-section of the through-hole  234  may have any suitable shape, for example, circular, oval, or any regular or irregular shape. 
     The opening of the through-holes  234  is shown in  FIGS. 11-12  as having a gradually increasing size toward the top of the sealing tool to increase the dissipation of the heat. However, the size and configuration of the drill through could be any shape or size, ranging from a straight sided drill through to any configuration that will surround the pill cavity and allow for the upward dissipation of the heat. 
     The sealing tool having at least one through-hole described above allows additional heat to dissipate through the top of the tool, thereby providing additional protection against the degradation of the heat sensitive holograms that are located beneath the openings. 
     In another aspect, the present disclosure also provides the resulting assembly, for example, those as described in  FIGS. 6, 10, and 12 . The present disclosure also provides the resulting pharmaceutical packs. 
     Although the subject matter has been described in terms of exemplary embodiments, it is not limited thereto. Rather, the appended claims should be construed broadly, to include other variants and embodiments, which may be made by those skilled in the art.