MX2008004201A - Lid sheet for use in a blister pack - Google Patents

Abstract

There is provided a lid sheet for use in a blister form pack for packaging of products, wherein said lid sheet is a laminate comprising four layers.

Description

COVER SHEET FOR USE IN A BUBBLE TYPE PACKAGING Cross Reference with Related Requests This patent application claims the priority of EP 05 405 561.1 published on September 27, 2005, the description of which is incorporated herein by reference in its entirety. Field of the Invention The present invention relates to a cover sheet for use in a removable bubble type packaging and suitable for packaging products (e.g., pharmaceutical and medical products). The present invention in particular relates to a tear-resistant, wear-resistant, wear-resistant cover sheet for use with cold-formed and thermoformed base sheets for composing said bubble-type package. BACKGROUND OF THE INVENTION The use of drug dispensers in the supply of drugs for the lung is well known. Said dispensers generally comprise a body or housing within which a carrier of the drug (i.e. medicament) is located. Known inhalation devices include those in which the drug carrier is in the form of a bubble-type pack (e.g., an elongated bubble-type strip) containing a number of discrete doses of the powdered medicament. In use, the bubble-type package is typically housed within the dispenser such that the bubbles can be transported through the dispenser in an indexed manner to allow access of discrete doses of the drug carried therein. Such devices usually contain a mechanism for individually accessing the doses contained within the bubbles. Known access mechanisms typically comprise either bubble piercing means or means for detaching a cover sheet from a base sheet of the bubble-type package. Thus, the powder medicine can be accessed and inhaled. Bubble-type packages having removable cover sheets are also suitable for the packaging of other products including other pharmaceutical and medical products, cosmetic products, food and non-food products and for other technical applications. It is desirable that the cover sheet of a tear-off bubble pack be strong enough to maintain its integrity during the opening of the package (e.g., by peelable separation of the cover sheet of a base sheet) within a medicament dispenser. It is also desirable that said cover sheet be strong enough to maintain its integrity throughout the lifetime of use of the medicament dispenser such as during the winding of the cover sheet once it is separated from the base sheet. The known elongated bubble strip that forms drug packages for use in inhalable drug containers in the form of dry powder is disclosed in applicant's pending PCT patent application No. WO2004 / 041672. The cover sheet thereof typically comprises a laminate that includes at least the following successive layers: (a) paper; attached to (b) plastic polymer film; attached to (c) aluminum foil. The plastic polymer film layer suitably comprises a material selected from the group consisting of polyester, polyamide, polypropylene and PVC. Typically, the aluminum foil layer of the cover sheet is also provided with a heat-adhesive lacquer layer, which is bonded with the inner layer of the base sheet. This connection is interrupted during the opening of the bubble strip by the removable removal of the cover sheet from the base sheet. Other medical and pharmaceutical products of bubble-type removable packaging with a protective function against moisture, gases and light typically have the following structure: • Lacquered / aluminum foil > 30μ ?? / sealing layer • Paper, 40-50 g / m2 / aluminum foil, 20-30 // m / sealing layer • OPA or PET film, 12-25 // m / aluminum foil, 20-25 pm I sealing layer • Paper, 20-50 g / m2 / OPA or PET film, 12-25 μ? / aluminum foil, 20-25 m / Sealing layer Applicant has found that the strength of the cover sheet can be increased by the use of non-conventional polymeric materials, particular for use in laminated sheets thereof which are additional to the layers of paper and aluminum foil. In particular, wear resistance and resistance to wear propagation of the cover sheet during use can be improved. In this way, bubble-shaped medicine packages including cover sheets can be obtained. Brief Description of the Invention In accordance with one aspect of the present invention, a cover sheet is provided for use in a bubble-shaped package for packaging products (eg pharmaceutical and medical), wherein said cover sheet is a laminate containing four layers A, B, C and D with the sequence of layers ABCD and the layers comprising the following: (Layer A) a layer A material selected from the group consisting of cellulose material (eg cellulose film or paper); aluminum foil; plastic film with a temperature resistance of at least 1 second at 220 ° C; Lacquer with a temperature resistance of at least 1 second at 220 ° C; and anti-adhesive cover; (Layer B) a layer B material selected from the group consisting of at least two unoriented, mono-oriented or biaxially oriented plastic films arranged at an angle and joined by means of lamination or hot calendering plastic coated with a structure of type net; a non-woven material made of a plastic polymer; at least one fiber or plastic film having a network type; a paper comprising a material selected from the group consisting of Polysulfone, PEN polyethylene naphthalate, polyphenylisulfone (PPSU), polyimide (Pl); Polyetherimide (PEI) and Tetrafluoroethylene / ethylene; and a multilayer paper consisting of at least two of the aforementioned materials; (Layer C) aluminum foil; and (Layer D) a heat-adhesive layer (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or heat-adhesive lacquer). The cover sheet ('cover paper') herein suitable for use as a wear-resistant cover sheet and resistant to wear propagation, for example for use with thermoformed and cold formed base sheets to form a bubble-type package to pack products that include pharmaceutical and medical products, cosmetic products, food and non-food products and for other technical applications.

These and other embodiments of the present invention are set forth in the following description, which describes, for illustrative purposes only, several of the embodiments thereof. Detailed Description of the Invention Suitably, layers A and B and layers B and C are joined using a lamination aid to achieve a bond strength of at least 2N / 15 mm. Suitable lamination aids are chosen in such a way that delamination of the laminate does not occur during the peelable opening of the bubble-type package. For example, laminating aids can be: • Solvent-based or solvent-free, aqueous, or single-component adhesives or • Extrusion resin as a monolayer or co-extruded.

Surprisingly it was found that the combination of the individual materials with different special physical and mechanical properties that ran along and cross-shaped to the machine direction together with the layers made of aluminum and heat-resistant lacquer provided a cover sheet of adequate hardness. Layers A to D have the following functions, in particular: • Layer A: Prevent adhesion of the laminate on the sealing machine. • Layer B: Prevent wear and propagation of wear of the cover sheet during opening. • Layer C: Vehicle with a barrier effect against moisture, gases and light • Layer D: Sealing layer for peelable opening The paper of layer A can be untreated, coated or satin (calendered) and suitably has a weight of 15 to 100 g / m2, preferably 20 to 50 g / m2. The aluminum foil of layer A suitably has a thickness of 6 to 60 μm, preferably 7 to 25 μm. The temperature-resistant plastic film of layer A suitably has a thickness of from 7 to 15 25, preferably from 12 to 25 pm. As an example, the temperature-resistant plastic film of layer A consists of Polyethylene Terephthalate (PET), Oriented Polyamide (OPA), Polysulfone (PSU), Polyphenylsulfone (PPSU), Polyaryletherketone (PEEK), Polyimide (Pl) or Polyetherimide (PEI) with an adequate thickness of 7 to 25 pm, preferably 12 to 25 pm. The plastic films of layer B consist for example of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), Polystyrene (PS), Polycarbonate (PC) , halogen-containing plastics; in particular Polyvinylchloride (PVC), Polyvinylidene chloride (PVDC), or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluoroethylene / ethylene or a combination of the aforementioned plastics and suitably have a thickness of 8 to 200 μm. , preferably from 12 to 100 p.m. Suitable plastic films can have a woven structure. The plastic cover of the network-like structure of layer B preferably consists of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE, or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), plastics containing halogen, in particular polyvinylchloride (PVC), polyvinylidene chloride (PVDC) or polychlorotrifluoroethylene (PCTFE) or albumen (silk) and has a preferred weight of 30 to 150 g / m2, particularly 40 to 120 g / m2. Suitable plastic coatings may have a woven structure. The non-woven material of layer B consists for example of HDPE (eg Tyvec®), Polyester (eg Spunbond® or Evolon®) Polyethylene terephthalate (PET) / Polybutylene terephthalate (PBT) with Polyamide 6 or Polyamide 6.6, Polyester with polyolefins, in particular PET with PP or Polyamide with polyolefins and suitably preferably has a surface weight of 10 to 120 g / m2. The paper consists of at least one fiber or plastic film having a network type (eg woven) of the B layer consisting for example of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE or HDPE, Polypropylene (PP) ), Polyester, Polyamide (PA), Polystyrene (PS), Polycarbonate (PC), halogen-containing plastics, in particular Polyvinylchloride (PVC), Polyvinylidene Chloride (PVDC) or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluorothylene / Ethylene or a combination of the aforementioned plastics and has a suitable thickness of 8 to 200 μm, preferably 12 to 80 μm. The individual films of the multilayer sheet of layer B consist for example of Polyethylene (PE), in particular VLDE, LLDPE, LMDPE, LDPE or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), Polystyrene (PS) , Polycarbonate (PC), plastics containing halogen, in particular Polyvinylchloride (PVC). Polyvinylidene chloride (PVDC) or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluoroethylene / ethylene or a combination of the aforementioned plastics and has a thickness of 8 to 200 μ? T ?, preferably 12 to 75 pm. The aluminum foil of layer C preferably has a suitable thickness of 7 to 60 μm, preferably 9 to 30 μm. As a means of thermo-adhesive lacquer, lacquers, plastic papers, and coatings can be used and allow an air-tight sealing of the cover sheet ('cover paper') to the interior of the base sheet and at the same time allow the removal of the cover sheet by detachment. Overprint of both the cover sheet and the base sheet is possible.

A bubble-shaped package for packaging pharmaceutical and medical products is also provided which contains (a) a base sheet in which bubbles are formed to define bags therein; and (b) a cover sheet as defined herein, and which can be sealed to the base sheet (e.g., except in the region of the bubbles) and mechanically peelable from the base sheet. Also provided is a bubble-shaped medication package (e.g., a formed package) comprising (a) a base sheet in which bubbles are formed to define bags therein to contain the inhalable medicament; (b) a cover sheet that can be sealed to the base sheet (eg except in the region of the bubbles) and mechanically (eg manually) peelable from the base sheet to allow release of said inhalable medicament, wherein said sheet The cover has a laminated structure comprising at least the following successive layers: (i) an outer paper cover sheet layer; united to (ii) a first layer of intermediate cover sheet of polymeric material; attached directly or indirectly to (iii) a sheet of aluminum foil cover sheet; attached directly or indirectly to (iv) a layer of heat-adhesive inner cover sheet (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-resistant lacquer). A bubble-shaped drug package (i.e. medicament) is provided comprising a base sheet and a cover sheet, each of the base and cover sheet having a particular shape as described in more detail hereafter. In embodiments, the drug package has different and multiple doses of the drug (i.e. separate) therein, and may, for example, be in the form of an elongated bubble strip, disc or other suitable bubble-type packaging. Preferably, the drug package is in the form of an elongated bubble strip. The base sheet is provided with bubbles that define bags to contain the inhalable drug. The bags can define any suitable profile including square, circular or rectangular or variations with rounded corners of the square and rectangular profiles. In modalities, two or more bags can be joined to a channel that during the inhalation process the powder is combined. The term "inhalable drug" is used herein to refer to a drug suitable for inhaled delivery to the lung. The cover sheet can be sealed to the base sheet except in the region of the bubbles and mechanically (e.g. manually) detach from the base sheet to allow release of the inhalable drug from an open pouch. Preferably, the drug package is in the form of an elongated bubble strip. The elongated bubble strip comprises a base sheet in the form of an elongated strip in which the bubbles are formed to define bags for containing the inhalable drug. Typically, one or more series of bubbles are arranged (e.g. in linear or zig-zag series or circular arrangement) along the base sheet. The cover sheet is sealed (e.g., hermetically) to the base sheet except in the region of the bubbles such that the cover sheet and the base sheet can be peeled off to release the inhalable drug from one or more bags. The base and cover sheets are typically sealed together across the entire width except for the forward end portions where they typically do not seal with each other. Therefore, the forward end portions of the base sheet and cover sheet are presented at the forward end of the elongated bubble strip. Sealing can be done by any of the known techniques (rotary, intermittent and a combination of flat bed and sealing roller). The joining of the cover sheet to the base sheet can be done in all known techniques, e.g. Contact heat, ultrasonic welding. In some embodiments, both the cover sheet and the base sheet of the drug packet herein are in the form of a laminate, comprising multiple layers of different materials. In other embodiments, the base sheet comprises a single material. The base sheet of the present typically comprises (i) a first layer of aluminum foil base sheet; and (ii) a second base sheet layer of polymeric material with a thickness of 10 to 150 microns. Typically, the second base sheet layer is arranged to join the inner cover sheet layer and this joint allows separation by detachment of these layers. The first foil layer of aluminum foil typically has a thickness of 15 to 120 microns, in particular 20 to 90 microns. The thickness of the second base sheet layer of polymeric material is 10 to 150 microns, such as 10 to 120 microns, preferably 15 to 100 microns. In embodiments, the second base sheet layer comprises a polymer material of low water vapor permeability. In embodiments, the water vapor permeability is less than 0.6 g / (100 inches2) (24 hours) (thousand) at 25 ° C, preferably less than 0.3 g / (100 inches2) (24 hours) (mil) at 25 ° C appropriately measured by ASTM E96-635 (E) which defines a standard test method for measuring the permeability of water vapor.

In embodiments, the polymeric material of the second base sheet layer comprises a material selected from the group consisting of polyvinyl chloride (PVC) (e.g., oriented or molded); polypropylene (e.g., oriented or molded, standard or metallocene); polyethylene (e.g. in the form of high density, low or intermediate, standard or metallocene); polyvinylidene chloride (PVDC); polychlorotrifluoroethylene (PCTFE); cyclic olefin copolymer (COC); and cyclic olefin polymer (COP). Optionally, other layers of material are also present. The material sold under the trade name Aclar by Honeywell Inc, a United States corporation is an appropriate polychlorotrifluoroethylene (PCTFE) polymer material herein. The suitable cyclic olefin copolymer (COC) is sold by Hoechst AG of Germany under the trade name Topaz. A suitable cyclic olefin polymer is sold by Nippon Zeon Co. Ltd of Tokyo, Japan under the trade name Zenor. In embodiments, the polypropylene polymer material and the polyethylene polymer material are manufactured by a process in which one or more metallocene compounds are used to modify and / or control the nature of any side chain group thereof. When the polymeric material of the second base sheet layer is selected from the group consisting of polyethylene (in the form of high density), polypropylene or polyvinylidene chloride (PVDC), penetration of reduced oxygen through the polymeric layer can be achieved, and as a result inside the bubble. The penetration of oxygen through the polymeric layer can be tested using an ASTM D3985-81 test method, wherein said oxygen transmission is measured at 25 ° C and 50% Relative Humidity. In embodiments, the first foil layer of foil is provided with an outer foil layer of a polymeric material, particularly oriented polyamide (OPA). As a result, the base sheet comprises an outer oriented polyamide (OPA) layer, which is bonded to (i) the first foil layer of aluminum foil; which is attached to (ii) the second base sheet layer of polymeric material with a thickness of 10 to 100 microns. The bond between the layers of the base sheet is conveniently provided as an adhesive bond (e.g., solvent-based adhesive in which the solvent is organic or water-based); bonding of solvent-free adhesive; extrusion laminated joint; or hot calendering. A particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) polyvinyl chloride (PVC). The thickness of the polyvinyl chloride (PVC) layer is 10 to 100 microns, in particular 50 to 100 microns.

Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) polyester. The thickness of the polyester layer is from 10 to 100 microns, particularly from 50 to 100 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) polypropylene. The thickness of the polypropylene layer is 10 to 100 microns, particularly 50 to 100 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded or laminated by extrusion to (c) oriented polypropylene (OPP). The thickness of the oriented polypropylene layer (OPP) is 10 to 60 microns, particularly 20 to 30 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) molded polypropylene. The thickness of the molded polypropylene layer is from 10 to 60 microns, particularly from 20 to 30 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded or laminated by extrusion to (c) high density polyethylene (HDPE). The thickness of the high density polyethylene (HDPE) layer is 10 to 100 microns, particularly 30 to 70 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded or laminated by extrusion to (c) low density polyethylene (LDPE). The thickness of the low density polyethylene (LDPE) layer is 10 to 80 microns, particularly 20 to 50 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) polyvinylidene chloride (PVDC). The thickness of the polyvinylidene chloride layer (PVDC) is 10 to 60 microns, particularly 20 to 30 microns. The PVDC grade is generally from 8 to 95 gsm, in particular from 10 to 40 gsm. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded to (c) polychlorotrifluoroethylene (PCTFE). The thickness of the polychlorotrifluoroethylene chloride layer (PCTFE) is 10 to 60 microns, particularly 20 to 45 microns. The polychlorotrifluoroethylene (PCTFE) layer can be oriented. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded or laminated by extrusion to (c) cyclic olefin copolymer (COC). The thickness of the cyclic olefin copolymer (COC) layer is from 10 to 60 microns, particularly from 20 to 30 microns. Another particular base sheet comprises the following successive layers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminum foil; adhesively bonded or laminated by extrusion to (c) cyclic olefin polymer (COP). The thickness of the cyclic olefin polymer (COC) layer is 10 to 60 microns, particularly 20 to 30 microns. The cover sheet of the drug package herein has a particular laminate structure. In one aspect of the present, the cover sheet has a laminated structure comprising at least the following successive layers: (i) an outer cover sheet layer of cellulose material (e.g. paper or cellulose film); attached to (ii) a first layer of intermediate cover sheet of polymeric material; attached directly or indirectly to (iii) a layer of aluminum foil cover sheet; bonded directly or indirectly to (iv) a layer of inner heat-resistant sheet (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-resistant lacquer). The thickness of each of the layers of the cover sheet can be selected according to the desired properties but is typically in the order of 3 to 200 microns, particularly 5 to 50 microns. The outer paper cover sheet layer typically comprises paper of size from 10 to 80 g / m2, particularly from 20 to 50 g / m2. The first layer of intermediate cover sheet of polymeric material adds strength to the cover sheet to increase wear resistance and resistance to wear propagation. The first layer of intermediate cover sheet of polymeric material conveniently has a thickness of 5 to 100 microns, particularly from 10 to 80 microns. In one aspect, the first intermediate cover sheet layer of polymeric material comprises woven polyamide, which for example defines a network-like structure. The interfolding of the woven polyamide layer to its adjacent layers is conveniently achieved as an adhesive lamination or an extrusion lamination. A particular cover sheet comprises (i) an outer paper cover sheet layer; attached to (i) a first layer of intermediate cover sheet of woven polyamide material with a thickness of 50 to 120 microns, particularly 50 to 100 microns; attached to (iii) a layer of aluminum foil cover sheet; attached to (iv) an inner sheet layer of heat-adhesive lacquer. In another aspect, the first optional intermediate layer of polymeric material comprises spun poly (ethylene terephthalate) (spun PET), which is a non-woven material. The spun PET has a weight typically of 10 to 250 g / m2, particularly of 20 to 60 g / m2. The crevice connection of the spun PET layer is conveniently achieved using extrusion lamination, particularly polyethylene extrusion (PE). Suitable spinning PET materials include those sold by Johns Manvilie of Waterville, Ohio under the trade names spunbond 488/20, spunbond 488/30 and spunbond 088/30. A particular cover sheet comprises (i) an outer paper cover sheet layer; which is joined using PE extrusion to (ii) a first layer of intermediate cover sheet of spun PET material with a weight of 10 to 80 g / m2; joined using PE extrusion to (iii) a sheet of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. Another particular cover sheet comprises (i) an outer paper cover sheet layer; which is joined using extrusion lamination to (ii) a first layer of intermediate cover sheet of spun PET material with a weight of 10 to 80 g / m2; joined using coextrusion lamination (one or two layers of co-extrusion) to (iii) a sheet of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. Another particular cover sheet comprises (i) an outer paper cover sheet layer; which is joined using lacquer lamination to (ii) a first layer of intermediate cover sheet of spun PET material with a weight of 10 to 80 g / m2; joined using lacquer lamination to (iii) a layer of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. In another aspect, the first optional intermediate layer of polymeric material comprises spun high-density polyethylene (spun HDPE), which is a non-woven material. The spun HDPE typically weighs 10 to 80 g / m2, particularly 20 to 60 g / m2. The crevice connection of the spun HDPE layer is conveniently achieved using extrusion lamination, particularly polyethylene (PE) extrusion. The material sold by Du Pont under the trade name Tyvek is a suitable spun HDPE sheet material. A particular cover sheet comprises (i) an outer paper cover sheet layer; which is joined using PE extrusion to (ii) a first layer of intermediate cover sheet of spun HDPE material with a weight of 10 to 80 g / m2; joined using PE extrusion to (iii) a sheet of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. In another aspect, the first optional intermediate layer of polymeric material comprises a cross-laminated high density polyethylene (HDPE). Cross-laminated HDPE means a material that contains at least two cross-laminated HDPE films with one another at a suitable cross-lamination angle, wherein the angle of cross lamination is typically 30 to 60 °, particularly 45 °. The cross-laminated HDPE typically has a thickness of 30 to 100 microns, particularly 50 to 80 microns. The material sold by Illinois Tool Works, Inc. under the trade name Valeron is a cross-laminated HDPE material suitable for the present. A particular cover sheet comprises (i) an outer paper cover sheet layer; attached to (ii) a first layer of intermediate cover sheet of cross-laminated HDPE material with a thickness of 30 to 100 microns, particularly 50 to 80 microns; attached to (iii) a sheet of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. In another aspect, the first optional intermediate layer of polymeric material comprises a cross-laminated polyethylene terephthalate (PET). By cross-laminated PET is meant a material containing at least two cross-laminated PET films with one another at a suitable cross-lamination angle, wherein the angle of cross-lamination is typically 30 to 60 °, particularly 45 °. Cross-laminated PET typically has a thickness of 30 to 100 microns, particularly 50 to 80 microns. A particular cover sheet comprises (i) an outer paper cover sheet layer; attached to (ii) a first layer of intermediate cover sheet of cross-laminated PET material with a thickness of 30 to 100 microns, particularly 50 to 80 microns; attached to (iii) a sheet of aluminum foil cover sheet; attached to (iv) a layer of an inner cover sheet of a heat-adhesive lacquer, a thermo-adhesive film or a thermo-adhesive extrusion coating. The thickness of the aluminum foil cover sheet layer is typically 10 to 60 microns, particularly 15 to 40 microns. The aluminum foil cover sheet layer is bonded directly or indirectly to the inner heat-sensitive foil sheet layer. When joined indirectly, one or more of the layers of the additional cover sheets is placed between the foil cover layer of foil and the inner foil cover sheet layer. The inner heat-sensitive cover sheet layer is arranged to be attached to the base sheet, typically to the second base sheet layer of polymeric material. The bond between the layers of the cover sheet is conveniently provided as an adhesive bond (e.g., solvent-based adhesive wherein the solvent is organic or water-based); a bond of solvent-free adhesive; an extrusion laminated joint; or hot calendered. In accordance with another aspect of the present invention there is provided a bubble-shaped package for drug containing (a) a base sheet in which bubbles are formed to define bags therein to contain the inhalable medicament; (b) a cover sheet that can be sealed to the base sheet, except in the region of the bubbles and mechanically peeled off from the base sheet to allow release of said inhalable medicament, wherein said cover sheet has a laminated structure that it comprises at least the following successive layers: (i) a cover sheet layer of external cellulose material (eg paper or cellulose film); attached directly or via an optional first intermediate layer of polymeric material to (ii) a layer of aluminum foil cover sheet; attached to (iii) a cover sheet layer of internal polymeric material. In this aspect, the base sheet can comprise any of the base sheet laminate structures described above; the outer paper cover sheet layer typically comprises paper with a size from 10 to 80 g / m2, particularly from 20 to 50 g / m2; and the thickness of the aluminum foil cover sheet layer is typically 10 to 60 microns, particularly 15 to 40 microns. The cover sheet layer of external cellulose material (e.g., paper or cellulose film) is attached directly or through an optional first intermediate layer of polymeric material to the foil sheet cover layer. In variations of the present, the outer paper cover sheet layer is absent. In some aspects, the (iii) inner cover sheet layer does not comprise a heat-adhesive lacquer component but another polymeric material (e.g., a film or extrusion coating). When this is the case, the cover sheet is more suitable for use with a base sheet having heat-adhesive lacquer or other substance capable of providing release function as its inner base sheet layer. In one aspect, the first optional intermediate layer of polymeric material comprises an extrusion layer of polyethylene (PE) and the inner shell sheet layer of polymeric material comprises a removable coextrusion coating (e.g., polyethylene / polybutylene). Examples of peelable coextrusion coating materials include those produced by Alean Packaging Singen GmbH: (1) intermediate extrusion layer (APS reference number: X2228EX): a copolymerisate of ethylene and ethylene acrylic acid provided by DOW Plastics; and (2) Coextrusion coating (APS No. X2253EX and X2311EX) where X2253EX is a random terpolymer of ethylene, butylacrylate and maleic anhydride provided by Arkema and X2311 EX is a polyethylene blend provided by Shuman and a copolymer of ethylene and acrylic ester provided by Arkema. Thus, a suitable package for drug comprises (i) an outer paper cover sheet layer; joined through an optional intermediate first extrusion layer by polyethylene (PE) to (ii) a layer of aluminum foil cover sheet; attached to (iii) a removable coextrusion coating inner cover sheet layer having a weight of about 5 to 50 g / m2, particularly 10 to 30 g / m2. In embodiments, the inner cover sheet layer of polymeric material comprises a release film. The release film is for example, a polyethylene (PE) film, a polyvinyl chloride (PVC) film or a polypropylene (PP) film. This release film is particularly suitable for a removable seal to an inner base sheet layer containing polyvinyl chloride (PVC) or polyethylene (PE). A suitable release film for sealing in polyethylene (PE) is produced by Nordenia Gronau GmbH of Germany (Alean commercial reference FSN097). A release film suitable for sealing in polyvinyl chloride (PVC) is produced by Nordenia Gronau GmbH of Germany (Alean commercial reference X3496FSN). In one aspect, there is no optional first intermediate layer of polymeric material and the inner cover sheet layer of polymeric material comprises a release film (eg a polyethylene (PE) release film, a release film of polyvinyl chloride (PVC). or a polypropylene (PP) release film). Therefore, a suitable cover sheet comprises an outer paper cover sheet layer; attached to (ii) a layer of aluminum foil cover sheet; attached to (iii) a layer of inner cover sheet of polyethylene (PE) peelable film of thickness from 10 to 80 microns, particularly from 15 to 50 microns. This cover sheet is particularly suitable for use with a base sheet having peelable PE film as its inner foil layer. Therefore, another suitable cover sheet comprises (i) an outer paper cover sheet layer; attached to (ii) a layer of aluminum foil cover sheet; attached to (iii) an inner cover sheet of polyvinyl (PVC) release film chloride of thickness from 10 to 80 microns, particularly from 20 to 50 microns. In a further aspect, the first optional intermediate layer of polymeric material comprises polyethylene terephthalate (PET) and the inner shell sheet layer of polymeric material comprises polyvinyl chloride (PVC). A package for drug therefore comprises (i) an outer paper cover sheet layer; bonded through a first optional intermediate layer of PET with a thickness of 5 to 30 microns, particularly 10 to 25 microns joined (ii) a layer of aluminum foil cover sheet; attached to (iii) a layer of PVC inner cover sheet of thickness from 5 to 50 microns, particularly from 30 to 40 microns. This cover sheet is particularly suitable for use with a base sheet having heat-resistant lacquer as its inner base sheet layer. In another aspect, the first optional intermediate layer of polymeric material comprises spun poly (ethylene terephthalate) (spun PET) and the inner cover sheet layer of polymeric material comprises a release film (eg a peelable polyethylene (PE) film, a release film of polyvinyl chloride (PVC) or a polypropylene (PP) release film). This cover sheet is particularly suitable for use with a base sheet having PVC as its inner base sheet layer. Spun PET typically has a weight of 10 to 250 g / m2, particularly from 20 to 60 g / m2. The crevice connection of the spun PET layer is conveniently achieved using extrusion lamination, particularly polyethylene extrusion (PE). Suitable spinning PET materials include those sold by Johns Manville under the trade names spunbond 10488/20, spunbond 488/30 and spunbond 088/30. Therefore, a suitable drug package comprises (i) an outer paper cover sheet layer; joined through a first optional intermediate layer of spun PET with a thickness of 10 to 60 microns, particularly 20 to 30 microns attached to (i) a layer of aluminum foil cover sheet; attached to (iii) an inner cover sheet layer of a release film having a thickness of 5 to 50 microns, particularly 10 to 40 microns. When the inner cover sheet layer is made of PE release film, this cover sheet is particularly suitable for use with a base sheet having PVC as its inner base sheet layer. In another aspect, the first optional intermediate layer of polymeric material comprises the first optional intermediate layer of polymeric material containing cross-laminated high density polyethylene (HDPE) and the inner cover sheet layer of polymeric material comprises a release film (eg a polyethylene (PE) release film, a polyvinyl chloride (PVC) release film, or a polypropylene (PP) release film). By "cross-laminated HDPE" is meant a material comprising at least two HDPE films cross-laminated to each other at a suitable cross-lamination angle, wherein the cross-lamination angle is typically 30 to 60 °, particularly 45 ° . The cross-laminated HDPE typically has a thickness of 30 to 100 microns, particularly 50 to 80 microns. The material sold by Illinois Tool Works, Inc. Under the trade name Valeron is a cross-laminated HDPE material suitable for the present. This cover sheet is particularly suitable for use with a base sheet having PVC as its inner base sheet layer. Therefore, a suitable drug package comprises (i) an outer paper cover sheet layer; bonded through an optional intermediate first layer of cross-laminated HDPE with a thickness of 30 to 100 microns, particularly 50 to 80 microns attached to (ii) a layer of aluminum foil cover sheet; attached to (iii) an inner cover sheet layer of a release film having a thickness of 5 to 50 microns, particularly 10 to 40 microns. When the inner cover sheet layer is made of PE release film, this cover sheet is particularly suitable for use with a base sheet having PVC as its inner base sheet layer.

Various known techniques can be used to join the cover sheet and the base sheet and thereby seal the bubble-type bags. Such methods include adhesive bonding, radiofrequency welding, ultrasonic welding, inductor sealing and hot rod sealing. The base sheet of the present is particularly suitable to be formed by 'cold-formed' methods (eg cold formation in one or two steps - advanced formation technology (AFT), cold forming in high pressure (HPCF)), which are carried out without heating the material of the base sheet. Such 'cold-form' methods are of particular utility when the drug or drug formulation for containment within the bubble is very sensitive to moisture, oxygen, other gases and / or flavors. To decrease the heat influence of the sealing process to avoid damage to the filling product, the sealing material is used with a low boiling point, e.g. polyethylene, polyethylene / metallocene; Surlyn® as sold by Du Pont. If the packaged product does not require a very high barrier to moisture and gases, the thermoforming of plastic materials such as PVC; Polypropylene; PVC / PVDC; PVC / Aclar® or COC laminates are used to form the bubble. A method for forming a package for drug herein comprises the steps of (a) providing a base sheet having a first contact surface and a cover sheet having a second contact surface, the base sheet includes at least one bag bubble type having a peripheral region, the bubble type bag is adapted to receive the composition of the drug; (b) filling the bubble bag with the pharmaceutical composition (e.g. in an amount of 10 to 3000 pg, such as 25 to 500 pg); (c) join the base sheet to the cover sheet to create a primary seal on it. The bubble-type bag can be in any form for a suitable air flow (e.g. to aid aerosolization of the powder contained therein), preferably, substantially elongated or substantially circular. In embodiments, the base sheet includes at least one first bonding material disposed on the first contact surface and the cover sheet includes at least one second bonding material disposed on the second contacting surface. In one embodiment, one or both of the bonding materials comprise at least one polymeric material. In a further embodiment, one or more of the first or second binding material comprises a substance that allows peelable separation e.g. a thermo-adhesive lacquer, a plastic film or coating. A suitable manufacturing system of the present invention comprises (a) a base conveyor for transporting a base sheet to the filling station, the base sheet includes at least one bubble-type bag adapted to receive an inhalable drug composition, the base sheet also includes a first bonding material; (b) a filling apparatus for filling the bubble bag with the inhalable drug composition; (c) a cover conveyor for transporting a cover sheet proximate to the filled base sheet, the cover sheet includes a second joining material; (d) a joining mechanism for joining the first and second joining material to create a primary seal therebetween. In use, the drug package herein is conveniently received in a drug dispenser comprising a housing for receiving the drug package. In one aspect, the drug dispenser has a unit shape and the housing is integral thereto. In another aspect, the drug dispenser is configured to receive a refill container and the housing is part of that refill container. In embodiments, the interior of the housing is shaped, or alternatively is provided with specific guiding features, to guide the drug package appropriately into the housing. In particular, the guide should ensure that the drug package is conveniently located to interact with internal mechanisms (e.g., indexing and opening mechanisms) of the housing. In embodiments, the dispenser has an internal mechanism for dispensing the various doses of the inhaled drug housed in the drug package for administration to the patient (e.g., by inhalation). In modalities, the mechanism contains a) receiving means for receiving the drug package; b) release means for releasing a dose of drug other than the drug package when it is received by said receiving means; c) an exit, placed in communication with the dose of the drug that can be released by said release means; d) addition means for individually indexing the different drug doses of the drug package; and The mechanism comprises receiving means (e.g., a receiving station) for receiving the drug package. The mechanism also comprises releasing means for releasing a dose of drug other than the drug package on receipt by the receiving station. The release means typically comprise means for mechanically detaching the bubble-type strip. An exit is placed in communication with the different doses of the drug that are released by said release means. The output can have any suitable form. In one aspect, it has the shape of a mouthpiece and in the other the shape of a vacuum for insertion into the nasal cavity of a patient. The outlet is preferably an individual outlet, which communicates with the different dose of drug that can be released by said release means through a common air channeling means (e.g. formed as a common air tube or manifold). Therefore, the patient can breathe through an individual outlet, and that breathing can be transferred by common channeling means for the dose of drug released, thus allowing its inhalation. The mechanism also comprises addition means for individually indexing the different drug doses of the drug package. Said addition typically occurs sequentially, for example accessing the sequentially arranged dose portions along the elongated carrier. Optionally, the drug dispenser also includes counting means for counting each time a drug dose other than the drug package is added to said addition means. In one aspect, the counting means are arranged to count each time a drug dose other than the drug package is added to said addition means. In embodiments, the addition means and the counting means are coupled directly or indirectly (e.g. through a coupling) with each other to allow counting of each indexing. In modalities, the means of counting are provided with (or communicated with) a screen to present the patient with the number of different doses remaining or the number of doses taken. In a preferred aspect, the drug dispenser takes the form of a dispenser for use with a drug package having multiple distinct pockets for containing the doses of the inhalable drug, wherein said pockets are spaced throughout and are defined between two detachable sheets secured to each other, said dispenser has an internal mechanism for dispensing the drug doses contained within said drug package, said mechanism contains, a) an opening station for receiving a bag from the drug package; b) releasable means positioned to retain a base sheet and a cover sheet of a bag that has been received in said opening station to detach said base sheet and cover sheet, to open said bag, said removable means include means for directing the cover for removing a cover sheet and a base sheet from a bag that has been received in said opening station; c) an exit, placed in communication with an open bag by which the user can access the drug dose of such open bag; d) addition means for individually indexing the different pouches of the drug package. In embodiments, the addition means comprises a rotary index wheel having gaps therein, said index wheel engaging with a drug package herein, in use with said drug dispenser such that said gaps receive a respective bag of the base sheet of a drug pack in the form of a bubble strip for use with said drug dispenser. Preferably, the drug dispenser has the general form as described in U.S. Pat. Núms. 5,860,419, 5,873,360 and 5,590,645 in the name of Glaxo Group Ltd, each of which is incorporated herein by reference. An example of a drug dispenser of this type is the well-known Diskus inhaler device (trademark) sold by GlaxoSmithKIine Pie. The drug dispenser can also be used as described in WO 03/061743 and WO 03/061744, the descriptions of which are incorporated by reference in their entirety. According to another aspect of the present invention there is provided a drug dispenser comprising (e.g., loaded with) at least one drug package herein. BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described with reference to the accompanying drawings, in which: Figure 1 shows a perspective view of the shape of a drug package in a suitable manner in accordance with the present invention; Figure 2 shows a top view of the shape of a drug package in a form suitable for use in accordance with the present invention; Figure 3 shows a top view of the form of another drug package in a form suitable for use in accordance with the present invention; and Figure 4 shows a cross-sectional side view of the shape of a drug package in the form of laminate according to the present invention; and Figure 5 shows a cross-sectional side view of the shape of a drug package in the form of laminate according to the present invention; and Figure 6 shows a cross-sectional side view of the shape of a drug package in the form of laminate according to the present invention; and Figure 7 shows a cross-sectional side view of the shape of a drug package in the form of laminate according to the present invention; and Figure 8 shows a cross-sectional side view of the shape of a cover sheet in the form of laminate according to the present invention.

Detailed Description of the Drawings Figure 1 shows a package for drug 100 that can be constructed to have a detailed form according to the present invention. The drug package comprises a flexible strip 101 which defines a plurality of bags 103, 105, 107 each of which contain a portion of a dose of drug that can be inhaled, in powder form.

The strip comprises a base sheet 109 in which the bubbles are formed to define the bags 103, 105, 107 and a cover sheet 111 which is hermetically sealed to the base sheet except in the region of the bubbles such that the sheet of cover 111 and base sheet 109 can be peeled off. The sheets 109, 111 are sealed with one another over the full width except for the front end portions 113, 115 where they preferably do not seal together. The cover sheets 111 and base 109 are formed of a laminate and adhere conveniently to each other by thermo-adhesion. Strip 101 is shown with elongated pouches 103, 105, and 107 running transversely to the length of strip 101. This is convenient since it allows a large number of pouches 103, 105, 107 to be provided in a strip length determined 101. Strip 101 may, for example, be provided with sixty or one hundred bags but it should be understood that strip 101 may have any number of suitable bags. Referring now to FIG. 2, a package for drug in the form of a laminate assembly or bubble strip 200 seen below is shown. The bubble strip has a substantially elongated shape and includes a plurality of bubbles 203, 205, 207 formed in the base 209 thereof adapted to receive a pharmaceutical composition, preferably in the form of a dry powder. Each bubble 203, 205, 207 has a length U that is preferably 1.5 to 15.0 mm, more preferably, 1.5 to 8.0 mm, and in a real mode is equal to 7.5 mm, measured along its axis, and a width b which is preferably from 1.5 to 10.0 mm, more preferably from 1.5 to 8.0 mm, and in a real mode is equal to 4.0 mm, measured along its shortest axis. In the illustrated example of Fig. 2, the bubble strip 200 has a width of 12.5 mm. The thickness of the base 209 is in the range of 75 to 200 microns. The thickness of the cover is in the range of 40 to 100 microns. The combined thickness of base 209 and cover (not visible) is approximately 115 to 300 microns. The bubbles 203, 205, 207 typically have spaces of 7.5 mm along the bubble strip 200. Each bubble 203, 205, 207 contains an effective dose of powder, preferably less than 30 mg of powder, more preferably, between - 25 mg of powder, and more preferably, about 12.5 mg of powder. The powder is an inhalable drug composition comprising at least one active drug. Suitable materials are used to build the base 209 and the cover (not visible). According to the invention, the base 209 and / or cover comprise laminate structures having at least one bonding material on at least one contact surface of either the base 209 or the cover. The bonding material preferably comprises at least one polymeric material and a heat-adhesive layer (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-sensitive lacquer such as a heat-adhesive vinyl lacquer). Referring now to Fig. 4, a bubble pack 400 is shown herein having a cover sheet having a four layer structure and comprising the following successive layers: (i) a layer of paper cover sheet external 425; attached to (ii) a first intermediate cover sheet layer of polymeric material 427; attached to (iii) a sheet of aluminum foil cover sheet 429; bonded directly or indirectly to (iv) a layer of inner heat-resistant cover sheet 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). A particular variety of cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; attached to (ii) a first layer of intermediate cover sheet 427 of woven polyamide material with a thickness of 50 to 120 microns; attached to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another variety of particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 20 g / m2; attached to (ii) a first layer of intermediate cover sheet 427 of woven polyamide material with a thickness of 50 to 120 microns; attached to (Mi) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; joined using PE extrusion to (ii) a first layer of intermediate cover sheet 427 of PET material spun with a weight of 30 g / m2; attached to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; joined using PE extrusion to (ii) a first layer of intermediate cover sheet 427 of PET material spun with a weight of 50 g / m2; attached to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; joined using extrusion lamination to (ii) a first layer of intermediate cover sheet 427 of 488/20 spun PET material with a weight of 20 g / m2; joined using two layers of coextrusion lamination to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; joined using lacquer lamination to (ii) a first layer of intermediate cover sheet 427 of 088/30 spun PET material with a weight of 30 g / m2; joined using two layers of lacquer lamination to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner heat-resistant cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). Another particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; joined using PE extrusion to (ii) a first layer of intermediate cover sheet 427 of spun HDPE material with a weight of 50 g / m2; joined using PE extrusion to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). A particular cover sheet comprises (i) an outer paper cover sheet layer 425 with a weight of 25 g / m2; attached to (ii) a first layer of intermediate cover sheet 427 of cross-laminated HDPE material with a weight of 25 g / m2; attached to (iii) a cover sheet layer of aluminum foil 429 with a thickness of 20 microns; attached to (iv) an inner thermo-adhesive cover sheet layer 430 (e.g., a heat-adhesive film, a heat-adhesive extrusion coating or a heat-adhesive lacquer). The material sold by Illinois Tool Works, Inc. under the tradename Valeron is a cross-laminated HDPE material suitable for layer 427. The base sheet of the bubble pack of Fig. 4 also has a multilayer structure and comprises the following successive layers: oriented polyamide (OPA) 420 adhesively bonded to aluminum foil 422 adhesively bonded to a base sheet layer 424 of polymeric material with a thickness of 10 to 100 microns. The bubble-type pack 400 is filled with an inhalable drug 414 in the dry powder form. In embodiments, the base sheet layer 424 of the polymeric material meets the requirement that the polymeric material has a permeability of less than 0.6 g / (100 inches2) (24 hours) (mil) at 25 ° C as measured by ASTM E96-635 (AND). In a particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: a layer of oriented polyamide (OPA) 420 with a thickness of 25 microns; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 100 microns. In a particular variation, the base sheet of the bubble pack of FIG. 4 has the following structure: layer of 25 microns in thickness of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 60 microns. In a particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 20 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; Adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 60 microns. In a particular variation, the base sheet of the bubble pack of FIG. 4 has the following structure: layer of 25 microns in thickness of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 30 microns. In a particular variation, the base sheet of the bubble pack of FIG. 4 has the following structure: layer of 25 microns in thickness of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; Adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 20 microns. In a particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 100 microns thick of PVC adhesively bonded to 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; adhesively bonded to polyvinyl chloride (PVC) 424 with a thickness of 15 microns. In a particular variation, the base sheet of the bubble pack of FIG. 4 has the following structure: layer of 25 microns in thickness of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 45 microns; adhesively bonded to polyvinylidene chloride (PVDC) 424 with a thickness of 30 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to oriented polypropylene 424 with a thickness of 20 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to molded polypropylene 424 with a thickness of 25 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to oriented polypropylene 424 with a thickness of 20 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to molded polypropylene 424 with a thickness of 20 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: 60 micron thick layer of polypropylene; adhesively bonded to a layer with a thickness of 25 microns of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to molded polypropylene 424 with a thickness of 25 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to polypropylene 424 with a thickness of 25 microns, wherein the polypropylene is manufactured by a process in which one or more metallocene compounds are used to control the side chain characteristics thereof. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to low density polyethylene (LDPE) 424 with a thickness of 40 microns.

In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns in thickness of oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to high density polyethylene (HDPE) 424 with a thickness of 40 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to polychlorotrifluoroethylene (PCTFE) 424 with a thickness of 20 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to cyclic olefin copolymer (COC) 424 with a thickness of 25 microns. In another particular variation, the base sheet of the bubble pack of Fig. 4 has the following structure: layer of 25 microns thick oriented polyamide (OPA) 420; adhesively bonded to aluminum foil 422 with a thickness of 60 microns; adhesively bonded to cyclic olefin polymer (COP) 424 with a thickness of 25 microns. Any of the variants of the particular cover sheet described with respect to Fig. 4 can be used in combination with any of the particular base sheet variants described with respect to the same Fig. 4. As will be appreciated by one skilled in the art, various conventional adhesives are used to join the laminate layers within the scope of the invention. Such adhesives include, but are not limited to, cyanoacrylates, acrylics and polyurethanes and resins for extrusion lamination, such as EAA, ionomer structures such as Surlyn® and Bynel® (trade names of Du Pont) and maleic anhydride acid (MAH resins). . During a typical process for manufacturing a drug package as shown in the example in Fig. 4, each bubble 412 is filled with a pharmaceutical composition 414 and subsequently sealed. The sealing temperature and other parameters of the sealing method may vary including setting, dwell time, sealing pressure and sealing speed. The heat sealing step joins the contact layers (e.g., PVC 424 and heat-setting lacquer 430) of the base and cover to seal each bubble 412 and, thus, forms a secure container for the pharmaceutical composition 414 contained therein. Ideally, the union creates an airtight seal that is formed. As will be appreciated, the sealing of each bubble 412 to eliminate the possibility of contamination of the external environment can be an important aspect of the manufacturing process. The figures. 5 and 6 show an alternative package for drug structures of the present, wherein the cover sheet is provided with an internal release layer. Referring now to FIG. 5, there is shown a bubble pack 700 of the present having a cover sheet having a three layer structure and comprising the following successive layers: (i) a layer of paper cover sheet external 725; attached to (ii) a layer of aluminum foil cover sheet 729; attached to (iii) an inner cover sheet layer of polymeric material 730. A particular cover sheet of FIG. 5 comprises (i) an outer paper cover sheet layer 725 with a weight of 25 g / m2; bonded by extrusion of polyethylene (PE) to (ii) a cover sheet layer of aluminum foil 729 thickness of 20 microns; attached to (iii) an inner cover sheet layer 730 of removable coextrusion coating having a weight of 15 g / m2. Another particular cover sheet of Fig. 5 comprises (i) an outer paper cover sheet layer 725 with a weight of 25 g / m2; attached to (ii) a layer of aluminum foil cover sheet 729 of thickness of 38 microns; attached to (iii) a layer of inner cover sheet of polyethylene (PE) release film with a thickness of 30 or 40 microns. The base sheet of the bubble-type packaging of Fig. 5 also has a multi-layer structure and comprises the following successive layers: oriented polyamide (OPA) 720 with a thickness of 25 microns adhesively bonded to aluminum foil 722 with a thickness of 45 microns adhesively bonded to a base sheet layer 724 of PE release film with a thickness of 30 microns. Bubble gasket 700 is filled with an inhalable drug 714 in the dry powder form. With reference now to Fig. 6, there is shown a bubble pack 800 of the present having a cover sheet having a three layer structure and comprising the following successive layers: (i) an outer paper cover sheet layer 825; attached to (i) an intermediate layer of polymeric material 827; attached to (iii) a layer of aluminum foil cover sheet 829; attached to (iv) an inner cover sheet layer of polymeric material 830. Thus, a particular drug package of FIG. 6 comprises (i) an outer paper cover sheet layer 825 with a weight of 25%. g / m2; attached to (ii) intermediate layer 827 of PET with a thickness of 12 microns attached to (iii) a cover sheet layer of aluminum foil 829 with a thickness of 20 microns; attached to (iv) a layer of inner cover sheet 830 of PVC film with a thickness of 15 or 30 microns. This cover sheet is particularly suitable for use with a base sheet having heat-resistant lacquer as its inner base sheet layer. As a result, the base sheet of the bubble-type packaging of Fig. 6 also has a multi-layer structure and comprises the following successive layers: oriented polyamide (OPA) 820 with a thickness of 25 microns adhesively bonded to aluminum foil 822 of thickness 60 microns adhesively bonded to a base sheet layer 824 of heat-adhesive lacquer. The bubble-type pack 800 is filled with inhalable drug 814 in the form of dry powder. Referring now to Fig. 7, there is shown a bubble pack 900 of the present having a cover sheet having a three layer structure and comprising the following successive layers: (i) a layer of paper cover sheet external 925; attached to (ii) an intermediate layer of polymeric material 927; attached to (iii) a layer of 92T aluminum foil cover sheet; attached to (iv) an inner cover sheet layer of polymeric material 930. As a result, a particular package for drug of FIG. 7 comprises (i) a layer of outer paper cover sheet 925 with a weight of 25 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of 488/20 spun PET with a thickness of 20 microns joined by two layers of coextrusion lamination to (iii) a cover sheet layer of 929 aluminum foil with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. As a result, another particular drug package of FIG. 7 comprises (i) an outer paper cover sheet layer 925 with a weight of 25 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of spun PET 488/30 with a thickness of 30 microns joined by two coextrusion lamination layers to (iii) a cover sheet layer of aluminum foil 929 with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. As a result, another particular drug package of FIG. 7 comprises (i) an outer paper cover sheet layer 925 with a weight of 25 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of spinning PET 088/30 with a thickness of 30 microns joined by two layers of coextrusion lamination to (iii) a cover sheet layer of aluminum foil 929 with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. As a result, another particular package for drug of Fig. 7 comprises (i) an outer paper cover sheet layer 925 with a weight of 50 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of spinning PET 088/30 with a thickness of 30 microns joined by two layers of coextrusion lamination to (iii) a cover sheet layer of aluminum foil 929 with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. As a result, another particular drug package of FIG. 7 comprises (i) an outer paper cover sheet layer 925 with a weight of 25 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of cross-laminated HDPE with a thickness of 60 microns bonded by lacquer lamination to (iii) a cover sheet layer of 929 aluminum foil with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. The material sold by Illinois Tool Works, Inc. under the trade name Valeron is a suitable cross-laminated HDPE material.

Therefore, another particular package for drug of Fig. 7 comprises (i) an outer paper sheet covering layer 925 with a weight of 50 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of cross-laminated HDPE with a thickness of 60 microns bonded by lacquer lamination to (iii) a cover sheet layer of 929 aluminum foil with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. The material sold by Illinois Tool Works, Inc. under the trade name Valeron is a suitable cross-laminated HDPE material.

Therefore, another particular package for drug of Fig. 7 comprises (i) an outer paper cover sheet layer 925 with a weight of 25 g / m2; bonded by extrusion lamination to (ii) intermediate layer 927 of cross-laminated HDPE with a thickness of 60 microns bonded by lacquer lamination to (iii) a cover sheet layer of 929 aluminum foil with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. The material sold by Illinois Tool Works, Inc. under the trade name Valeron is a suitable cross-laminated HDPE material.

Therefore, another particular package for drug of Fig. 7 comprises (i) an outer paper sheet covering layer 925 with a weight of 50 g / m2; bonded by lacquer lamination to (ii) intermediate layer 927 of cross-laminated HDPE with a thickness of 60 microns bonded by lacquer lamination to (iii) a cover layer of 929 aluminum foil with a thickness of 20 microns; bonded by lacquer lamination to (iv) a layer of inner cover sheet 930 of PE release film having a thickness of 30 microns. The material sold by Illinois Tool Works, Inc. under the trade name Valeron is a suitable cross-laminated HDPE material. As a result, the base sheet of the bubble-type packaging of Fig. 7 also has a multi-layer structure and comprises the following successive layers: oriented polyamide (OPA) 920 with a thickness of 25 microns adhesively bonded to 922 aluminum foil with a thickness of 60 microns adhesively bonded to the base sheet layer 924 with a thickness of 15 to 100 microns of PVC. The bubble-type pack 900 is filled with inhalable drug 914 in the form of dry powder. In other embodiments, the respective cover sheets of the Figures. 5 to 7 of the present may also be employed with any of the base sheets of Fig. 4 herein. Various patterns and joining patterns can be used to join and seal the bubble strip packages such as those shown in the Figures. 4 to 7. The patterns and patterns of union shown in Figures 2 and 3 are illustrative.

Now with reference to Fig. 2, a bonding scheme employing heat uniformly distributed substantially through at least one bubble strip surface 200 is shown to create discrete bond areas of the contact base 209 and the surfaces covering. Although several joining patterns can be formed by this joining scheme (e.g., zig-zag, dots, checkered, etc.), a checkered grid pattern 216 is employed in this example. As illustrated in FIG. 2, the grid 216 provides a restricted, tortuous path (generally designated by the M-arrow) for the entry of contaminants and / or moisture into the bubbles 203, 205, 207. Referring now to FIG. 3, another bonding scheme employing heat evenly distributed substantially through at least one bubble strip surface 300 is shown to create discrete bond areas of the contact base 309 and the cover surfaces. In this example a knurling joint pattern 316 is employed. Knurling 316 provides a restricted, tortuous path (generally designated by the M-arrow) for the ingress of contaminants and / or moisture into the bubbles 303, 305, 307. FIG. 8 shows a cover sheet ('cover paper') 1011 suitable for use in a bubble-type packaging of the present (not shown) and having the following layer structure from the outside in: Layer A 1025 for example, made of satin paper superimposed with a weight of 30 g / m2; Rolling aid 1026; Layer B 1027 for example, made of a non-woven material of HDPE with a weight of 60 g / m2; Rolling aid 1028; Layer C 1029 for example, made of aluminum foil with a thickness of 25 μm; and Layer D 1030, for example, made of heat-resistant lacquer. The cover sheet of the present drug pack is designed to provide greater resistance to wear and resistance to propagation to wear. Wear resistance is a measure of the strength of the cover sheet in the initial wear of the cover and is generally related to the properties of the tensile strength and puncture resistance of at least one layer of the cover sheet, generally a layer of polymeric material. Resistance to wear propagation is a measure of the strength of the cover sheet to wear once an initial wear (or nick or cut or similar) has been experienced by the cover sheet and in existing cover sheets is related generally to the properties of the paper and layer of aluminum foil cover sheet. The wear resistance can be measured in the laboratory by the ASTM method that has the reference number ASTM D1004. The resistance to wear propagation can be measured in the laboratory by a method called the Elmendorf test (DIN 53128 or EN21974). The cover sheet of the drug package of the present conveniently has a wear resistance of more than 20N and a resistance to wear propagation of more than 2.5N. The drug package and the related drug delivery device of the invention are suitable for delivering pharmaceutical products particularly for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD), bronchitis and chest infections. Other applications are also contemplated. Appropriate drugs can be selected from, for example, analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. as the sodium salt), ketotifen or nedocromil (e.g. as the sodium salt); anti-infectives e.g., cephalosporins, penicillins, streptomycin, sulfonamides, tetracyclines and pentamidine; antihistamines, e.g., metapyrylene; anti-inflammatory, e.g., beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. as the propionate ester), flunisolide, budesonide, rofleponide, mometasone e.g. as the furcation ester), ciclesonide, triamcinolone (eg as acetonide) or 6a, 9a-difluoro-11β-hydroxy-6a-methyl-3-oxo-17a-propionyloxy-androsta-1,4-dienic acid. 17 p-carbothioic ester S- (2-oxo-tetrahydro-furan-3-yl), (6a, 11β, 16 a, 17 a) -6,9-difluoro-17-. { [(fluorometyl) thio] carbonyl} -11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl-2-furoate, and (6 a, 11 b, 16 a, 17 a) -6,9-difluoro- 17-. { [(f I uorom et il) thio] coal i l} -11-hydroxy-16-methyl-3-oxoa nd rosta-, 4-dien-i-7-l-4-methyl-1,3-thiazole-5-carboxylate; antitussives, e.g., noscapine; bronchodilators, eg, 3- (4-. {[[6- ( { (2R) -2-hydroxy-2- [4-hydroxy-3- (hydroxymethyl) phenyl] ethyl} amino) hexyl] oxy .}. butyl) benzenesulfonamide, 3- (3. {[[7- ( { (2R) -2-hydroxy-2- [4-hydroxy-3-hydroxymethyl) phenyl] ethyl} -amino) heptyl] oxy} propyl) benzenesulfonamide, 4-. { (1 R) -2 - [(6- { 2 - [(2,6-dichlorobenzyl) oxy] ethoxy} hexyl) amino] -1-hydroxyethyl} -2- (hydroxymethyl) phenol, 4-. { (1 R) -2 - [(6- { 4- [3- (Cyclopentylsulfonyl) phenyl] butoxy}. Hexyl) amino] -1-hydroxyethyl} -2- (hydroxymethyl) phenol, N- [2-hydroxyl-5- [(1 R) -1-hydroxy-2 - [[2-4 - [[(2R) -2-hydroxy-2-phenylethyl] amino ] phenyl] ethyl] amino] ethyl] phenyl] formamide, N-2. { 2- [4- (3-phenyl-4-methoxyphenyl) aminophenyl] ethyl} -2-hydroxy-2- (8-hydroxy-2 (1 H) -quinolinon-5-yl) et lamina, 5 - [(R) -2- (2-. {4- [4- (2 -amino-2-methyl-propoxy) -phenylamino] -phenyl.}. -ethylamino) -1-hydroxy-ethyl] -8-hydroxy-1 H -quinolin-2-one, 5- [(1 R) -2 - [(5,6-Diethyl-2,3-dihydro-1 H -inden-2-yl) amino] -1-hydroxyethyl] -8-hydroxy-2 (1 H ) -quinolinone, albuterol (eg as a free base or sulfate), salmeterol (eg as xinafoate), ephedrine, adrenaline, fenoterol (eg as hydrobromide), formoterol (eg as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (eg as acetate), reproterol (eg as hydrochloride), rimiteroi, terbutaline (eg as sulphate), isoetarin, tulobuterol or 4-hydroxy-7- [2 - [[2 - [[3- (2-phenylethoxy) propyl] ] sulfonyl] ethyl] amino] ethyl-2 (3H) -benzothiazolone; adenosine agonists 2a, e.g. 2R, 3R, 4S, 5R) -2- [6-Amino-2- (1 S-hydroxymethyl-2-phenyl-ethylamino) -purin-9-yl] -5- (2-ethyl-2H-tetrazole-5 -il) -tetrahydro-furan-3 > 4-diol (e.g. as a maleate); integrin a4 inhibitors e.g. (2S) -3- [4- ( { [4- (aminocarbonyl) -1- piperidinyl] carbonyl} oxy) phenyl] -2 - [((2S) -4-methyl-2-. { . [2- (2-methylphenoxy) acetyl] amino.}. Pentanoyl) amino] propanoic (eg as free acid or potassium salt), diuretics, eg, amiloride; anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, e.g., aminophylline, choline theophyllinate, Usin theophyllinate or theophylline; therapeutic proteins and peptides, e.g., insulin or glucagon; vaccines, diagnostics, and gene therapies. It will be clear to a person skilled in the art that, when appropriate, the drugs can be used in the form of salts, (eg, as alkali metal salts or amines or as acid addition salts) or as esters (eg, esters) lower alkyl) or as solvates (eg, hydrates) to optimize the activity and / or stability of the drug. The drug product may in some aspects be a mono therapy product (i.e. containing an individual active drug) or it may be a combination therapy product (i.e. containing a plurality of active drugs). The drugs or drug components of a combination therapy product are typically selected from the group consisting of anti-inflammatory agents (e.g., a corticosteroid or an NSAID), anticholinergic agents (e.g., a Mi, M2, Malviz receptor antagonist). or M3), other p2-adrenoreceptor agonists, anti-infective agents (eg an antibiotic or an antiviral), and antihistamines. All suitable combinations are contemplated. Suitable anti-inflammatory agents include corticosteroids and NSAIDs. Suitable corticosteroids that can be used in combination with the compounds of the invention are those oral and inhaled corticosteroids and their prodrugs that have an anti-inflammatory activity. Examples include methyl prednisolone, prednisolone, dexamethasone, fluticasone propionate, 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11β-hydroxy-6a-methyl-3-oxo-androsta-1,4 acid. -dien-17 -carbothioic S-fluoromethyl ester, 6a, 9a-difluoro-1 p-hydroxy-16a-methyl-3-oxo-17a-propionyloxy-androsta-1,4-dien-17 -carbothioic ester S- ( 2-oxo-tetrahydro-furan-3S-il), beclomethasone esters (eg 17-propionate ester or 17.21 -dipropionate ester), budesonide, flunisolide, mometasone esters (eg furoate ester), acetonide triamcinolone, rofleponide, ciclesonide, butixocort propionate, RPR-106541, and ST-126. Preferred corticosteroids include fluticasone propionate, 6a, 9a-difluoro-11β-hydroxy-6a-methyl-17a - [(4-methyl-1,3-thiazole-5-carbonyl) oxy] -3-oxo-6-acid. androsta-1, 4-dien-17p-carbothioic S-fluoromethyl ester and 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11-hydroxy-16a-methyl-3-oxo-androsta-1 acid, 4-Dien-17β-carbothioic S-fluoromethyl ester, more preferably 6a, 9a-difluoro-17a- [(2-furanylcarbonyl) oxy] -11β-hydroxy-6a-methyl-3-oxo-androsta-1 acid, 4-dien-17 -carbothioic ester S-fluoromethyl. Suitable NSAIDs include sodium cromoglycate, nedocromil sodium, phosphodiesterase (PDE) inhibitors (eg theophylline, PDE4 inhibitors or mixed PDE3 / PDE4 inhibitors), leukotriene antagonists, leukotriene synthesis inhibitors, NOS inhibitors, tryptase inhibitors and elastase, beta-2 integrin antagonists and adenosine receptor agonists or antagonists (eg adenosine 2a agonists), cytokine antagonists (eg chemokine antagonists) or inhibitors of cytokine synthesis. Other suitable 32-adrenoreceptor agonists include salmeterol (e.g., as the xinafoate), salbutamol (e.g. as the sulfate or free base), formoterol (e.g. as the fumarate), fenoterol or terbutaline and salts thereof. Suitable phosphodiesterase 4 (PDE4) inhibitors include compounds that are known to inhibit the PDE4 enzyme or that were discovered to act as a PDE4 inhibitor, and that they are only PDE4 inhibitors, not compounds that inhibit other members of the PDE family as well as PDE4. It is generally preferable to use a PDE4 inhibitor that has an IC50 index of about 0.1 or more with respect to IC50 for the catalytic form of PDE4 which binds rolipram with a high affinity divided by IC50 for the form binding the rolipram with a low affinity. For purposes of this description, the cAMP catalytic site that binds the rolipram R and S with a low affinity is termed the "low affinity" binding site (LPDE 4) and the other form of this catalytic site that binds the rolipram with a High affinity is termed the "high affinity" binding site (HPDE 4). This term "HPDE4" should not be confused with the term "hPDE4" which is used to denote the human PDE4. A method for determining the IC50S indices is set forth in U.S. Pat. 5,998,428 which is incorporated herein by reference. See also application WO 00/51599 for another description of said test. Suitable PDE4 inhibitors include those compounds that have a healthy therapeutic index, Le., Compounds that preferably inhibit the catalytic activity of cAMP wherein the enzyme is in the form that binds rolipram with a low affinity, thereby reducing the side effects that apparently they are linked to the inhibition of the form that binds the rolipram with a high affinity. Another way to establish this is that the preferred compounds will have an IC50 index of about 0.1 or more with respect to the IC50 index for the catalytic form of PDE4 that binds rolipram with a high affinity divided by IC50 for the form that binds the rolipram with a low affinity. Another modification of this standard is one in which the PDE4 inhibitor has an IC50 index of about 0.1 or higher; said index is the index of the IC50 value to compete with the binding of 1nM of [3H] R-rolipram to a form of PDE4 that binds the rolipram with a high affinity on the IC50 value to inhibit the catalytic activity of PDE4 in a way that binds the rolipram with a low affinity using 1 μ? [3?] - ???? as the substrate. The most suitable are those PDE4 inhibitors that have an IC50 index of more than 0.5, and particularly those compounds that have an index of more than 1.0. Preferred compounds are c / 's 4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid, 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan -1-one and c / 's- [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxy-phenyl) -cyclohexan-1-yl]; these are examples of compounds that preferably bind to the low affinity binding site and have an IC50 index of 0.1 or greater.

Other suitable drug compounds include: c / 's-4-cyano-4- [3- (cyclopentyl i) -4-methoxyphenyl] cyclohexane-1-carboxylic acid (also known as cilomalast) described in U.S. Pat. . 5,552,438 and its salts, esters, pro-drugs or physical forms; AWD-12-281 from elbion (Hofgen, N. et al 15th EFMC Int Symp Med Chem (Sept. 6-10, Edinburgh) 1998, Abst P.98; CAS No. 247584020-9); a 9-benzyl adenine derivative nominated NCS-613 (INSERM); D-4418 of Chiroscience and Schering-Plow; a benzodiazepine PDE4 inhibitor identified as CI-1018 (PD-168787) and attributed to Pfizer; a benzodioxole derivative described by Kyowa Hakko in W099 / 16766; K-34 of Kyowa Hakko; V-11294A by Napp (Landells, LJ, et al., Eur Resp J [Annu Cong Eur Resp Soc (Sept 19-23, Geneva) 1998] 1998, 12 (Suppl 28): Abst P2393); roflumilast (Cat. No. 162401-32-3) and a phthalazinone (WO99 / 47505, the disclosure of which is incorporated herein by reference) by Byk-Gulden; Pumafentrine, (-) - p - [(4a R *, 10 £ »S *) - 9-ethoxy-1, 2,3,4,4a, 10b-hexahydro-8-methoxy-2-methylbenzo [c] [ 1,6] naphthyridin-6-yl] -N, N-diisopropylbenzamide which is a mixed inhibitor of PDE3 / PDE4 which has been prepared and published in and by Byk-Gulden, now Altana; arofiline developed by Almirall-Prodesfarma; VM554 / UM565 from Vemalis; or T-440 (Tanabe Seiyaku, Fuji, K. et al., J. Farmacol Exp Ther, 1998, 284 (1): 162), and T2585. Suitable anticholinergic agents are those compounds which act as antagonists at the muscarinic receptor, in particular those compounds which are antagonists of the M ^ and M2 receptors. Exemplary compounds include the alkaloids of belladonna plants as illustrated by the like of atropine, scopolamine, homatropine, hyoscyamine; these compounds are normally administered as a salt, being tertiary amines. Particularly suitable anticholinergics include ipratropium (e.g. as the bromide), sold under the name Atrovent, oxitropium (e.g. as the bromide) and tiotropium (e.g. as the bromide) (CAS-139404-48-1). Also of interest are: metantelin (CAS-53-46-3), propantheline bromide (CAS-50-34-9), anisotropin methyl bromide or Valpin 50 (CAS- 80-50-2), clidinium bromide ( Quarzan, CAS-3485-62-9), copyrrolate (Robinul), isopropamide iodide (CAS-71 -81-8), mepenzolate bromide (US Patent 2,918,408), tridihexetyl chloride (Pathilone, CAS- 4310-35-4), and hexcyclic methylsulfate (Tral, CAS-115-63-9). See also cyclopentolate hydrochloride (CAS-5870-29-1), tropicamide (CAS-1508-75-4), trihexyphenidyl hydrochloride (CAS-144-11 -6), pirenzepine (CAS-29868-97-1), Telenzepine (CAS-80880-90-9), AF-DX 116, or methoctramine, and the compounds described in WO01 / 04118. Suitable antihistamines (also referred to as ^ receptor antagonists) include one or more of the numerous known antagonists that inhibit Hi receptors, and are safe for human use. All are competitive, reversible inhibitors of histamine interaction with Hi receptors. Examples include ethanolamines, ethylenediamines, and alkylamines. In addition, other first generation antihistamines include those that can be characterized as being based on piperizine and phenothiazines. The second generation antagonists, which are not sedatives, have a similar activity-structure relationship in that they retain the central ethylene group (the alkylamines) or copy the tertiary amine group with piperizine or piperidine. Exemplary antagonists are the following: Ethanolamines: carbinoxamine maleate, clemastine fumarate, diphenylhydramine hydrochloride, and dimenhydrinate. Ethylenediamines: pyrilamine maleate, tripelennamine HCI, and tripelennamine citrate. Alkylamines: clofeniramine and its salts such as maleate salt, and acrivastine. Piperazines: HCI hydroxyzine, hydroxyzine pamoate, HCI cyclizine, lactate cyclizine, meclizine HCI, and cetirizine HCI. Piperidines: Astemizole, levocabastine HCl, loratadine or its analogue descarboethoxy, and terfenadine and fexofenadine hydrochloride or another pharmaceutically acceptable salt. Azelastine hydrochloride is another Hi receptor antagonist that can be used in combination with a PDE4 inhibitor.

Particularly suitable antihistamines include metapyrylene and loratadine. With respect to the combination products, the co-formulation compatibility is generally determined on an experimental basis by known methods and may depend on the chosen type of drug dispenser. The drug components of a combination product are conveniently selected from the group consisting of anti-inflammatory agents (e.g., a corticosteroid or an NSAID), anticholinergic agents (e.g., a Mi, M2, M- / M2 receptor antagonist). or M3), other 2-adrenoreceptor agonists, anti-infective agents (eg an antibiotic or an antiviral), and antihistamines. All suitable combinations are contemplated. In embodiments, compatible components of co-formulation comprise a p2-adrenoreceptor agonist and a corticosteroid; and the incompatible co-formulation component comprises an inhibitor PDE-4 inhibitor, an anti-cholinergic or a mixture thereof. The 2-adrenoreceptor agonists may for example be salbutamol (e.g., as the free base or the sulfate salt) or salmeterol (e.g., as the xinafoate salt) or formoterol (e.g. as the fumarate salt). The corticosteroid may for example be an ester of beclomethasone (e.g., dipropionate) or an ester of fluticasone (e.g., propionate) or budesonide.

In one example, the components compatible with the co-formulation comprise fluticasone propionate and salmeterol, or a salt thereof (particularly the xinafoate salt) and the component incompatible with the co-formulation comprises a PDE-4 inhibitor, an anticholinergic ( eg ipratropium bromide or tiotropium bromide) or a mixture thereof. In another example, the components compatible with the co-formulation comprise budesonide and formoterol (eg as the fumarate salt) and the component compatible with the co-formulation comprises a PDE-4 inhibitor, an anti-cholinergic (eg ipratropium bromide or tiotropium bromide) or a mixture thereof. In general, powdered drug particles suitable for delivery to the bronchial or alveolar region of the lung have an aerodynamic diameter of less than 10 microns, preferably less than 6 microns. Particles of other sizes may be used if delivery to other portions of the respiratory tract, such as the nasal cavity, mouth or throat, is desired. The medicament can be supplied as a pure drug, but it is preferable and more appropriate that the drugs are supplied together with excipients (carriers) which are suitable for inhalation. Suitable excipients include organic excipients such as polysaccharides (i.e. starch, cellulose and the like), lactose, glucose, mannitol, amino acids, and maltodextrins, and inorganic excipients such as calcium carbonate or sodium chloride. Lactose is a preferred excipient. The powdered drug and / or excipient particles can be produced by conventional techniques, for example by micronization, milling or calibration. In addition, the powders of the medicaments and / or excipients can be maneuvered with particular densities, scales of size or characteristics. The particles may comprise active agents, surfactants, wall-forming materials or other components that are considered desirable by one skilled in the art. The excipient can be included with a drug through well-known methods, such as mixing, co-precipitating and the like. Mixtures of excipients and drugs are typically formulated to allow precise measurement and dispersion of the mixture in doses. A standard mixture, for example, contains 13,000 micrograms of lactose mixed with 50 micrograms of the drug, giving a drug-to-drug ratio of 260: 1. The rates of dose mixes with drug excipient of 100: 1 to 1: 1 can be used. At very low ratios of excipient to drug, however, the reproducibility of the drug dose may become more variable. The drug package and the dispensing device of the invention is in a suitable aspect for dispensing the medicament for the treatment of respiratory disorders such as disorders of the lungs and bronchial passages, including asthma and chronic obstructive pulmonary disorder (COPD). In another aspect, the invention is suitable for delivering drug for the treatment of a condition that requires treatment by the systemic circulation of the drug, for example migraine, diabetes, pain relief e.g. inhaled morphine. Also, the use of a drug package and dispensing device according to the invention for the treatment of a respiratory disorder, such as asthma and COPD, is provided. Alternatively, the present invention provides a method for treating a respiratory disorder such as, for example, asthma and COPD, which comprises administering by inhalation an effective amount of drug product as described herein for a drug or device package. Dispatcher of the present invention. The amount of any particular drug compound or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof that is required to achieve a therapeutic effect will, of course, vary with the particular compound, the route of administration, the subject being treated, and the particular disorder or disease treated. Medications for the treatment of respiratory disorders of the present can, for example, be administered by inhalation at a dose of 0.0005 mg to 10 mg, preferably 0.005 mg to 0.5 mg. The dosage scale for adult humans is generally from 0.0005 mg to 100 mg per day and preferably 0.01 mg to 1 mg per day. It should be understood that the present disclosure is solely for the purpose of illustration and the invention extends to modifications, variations and improvements thereto. The application of which this description and claims are a part may be used as a basis for the priority related to any subsequent application. The claims of said subsequent application may be directed to any characteristic or combination of features described therein. They may take the form of product, method or use and may include, by way of example and without limitation, one or more of the following claims:

Claims (75)

1. CLAIMS 1. A cover sheet for use in the bubble-type package for packaging pharmaceutical and medical products, wherein said cover sheet is a laminate comprising four layers A, B, C and D with the ABCD layer sequence and the layers they are as follows: (Layer A) a layer A material selected from the group consisting of cellulose material (eg cellulose film or paper); aluminum foil; plastic film with a temperature resistance of at least 1 second at 220 ° C; Lacquer with a temperature resistance of at least 1 second at 220 ° C; and anti-adhesive cover; (Layer B) a layer B material selected from the group consisting of at least two non-oriented, mono-oriented or biaxially oriented plastic films arranged at an angle and joined by means of rolling or hot calendering or plastic coating with a structure of network type; a non-woven material made of a plastic polymer; at least one fiber or plastic film having a network type; a paper comprising a material selected from the group consisting of Polysulfone, PEN polyethylene naphthalate, polyphenylsulfone (PPSU), polyimide (Pl); Polyetherimide (PEI) and Tetrafluoroethylene / ethylene; and a multilayer paper consisting of at least two of the aforementioned materials; (Layer C) aluminum foil; and (Layer D) a heat-adhesive layer.
2. 2. A cover sheet according to claim 1, wherein layers A and B and layers B and C that join using a rolling aid to achieve bond strength of at least 2N / 15 mm.
3. 3. A cover sheet according to any of claims 1 or 2, wherein the paper of the layer A can be untreated, coated or satin and has a weight of 15 to 100 g / m2, preferably 20 to 80 g / m2.
4. 4. A cover sheet according to any of claims 1 or 2, wherein the aluminum foil of layer A has a thickness of 6 to 60 μm, preferably 7 to 25 μm.
5. 5. A cover sheet according to any of claims 1 or 2, wherein the temperature-resistant plastic film of the layer A has a thickness of 7 to 25 μ ??, preferably 12 to 25 μ?. .
6. 6. A cover sheet according to any of claims 1 or 2, wherein the temperature-resistant plastic film of layer A consists of polyethylene terephthalate (PET), oriented polyamide (OPA), polysulfone (PSU), Polyphenylsulfone (PPSU), Polyaryletherketone (PEEK), Polyimide (Pl), Polyetherimide (PEI) or Tetrafluoroethylene / Ethylene and has a thickness of 7 to 25 μm, preferably 12 to 25 μm.
7. 7. A cover sheet according to any of claims 1 to 6, wherein the plastic film of layer B consists of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), Polystyrene (PS), Polycarbonate (PC), halogen-containing plastics; in particular Polyvinylchloride (PVC), Polyvinylidene chloride (PVDC), or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluoroethylene or a combination of the aforementioned plastics and have a thickness of 8 to 200 μ? t ?, preferably from 12 to 100 pm.
8. 8. A cover sheet according to any of claims 1 to 6, wherein the plastic cover of the network structure of layer B consists of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE, or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), halogen-containing plastics, in particular Polyvinylchloride (PVC), Polyvinylidene chloride (PVDC) or Polychlorotrifluoroethylene (PCTFE), Tetrafluoroethylene / ethylene or a protein (satin) and has a preferred weight of 30 to 150 g / m2, particularly 40 to 120 g / m2.
9. 9. A cover sheet according to any of claims 1 to 6, wherein the non-woven material of layer B consists for example of HDPE, Polyester, PET7 Polybutylene terephthalate (PBT) with Polyamide 6 or Polyamide 6.6, Polyester with polyolefins, in particular PET with PP or Polyamide with polyolefins, Tetrafluoroethylene / ethylene and has a weight of 10 to 120 g / m2.
10. A cover sheet according to any one of claims 1 to 6, wherein the paper consists of at least one fiber or plastic film of layer B having a network type consisting of Polyethylene (PE), in particular VLDPE, LLDPE, LMDPE, LDPE or HDPE, Polypropylene (PP), Polyester, Polyamide (PA), Polystyrene (PS), Polycarbonate (PC), Plastics containing halogen; in particular Polyvinylchloride (PVC), Polyvinylidene chloride (PVDC), or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluoroethylene / ethylene or a combination of the aforementioned plastics and suitably have a thickness of 8 to 200 μ ? p, preferably 12 to 80 μ ?? A cover sheet according to any of claims 1 to 6, wherein the individual films of the multilayer sheet of layer B consist of Polyethylene (PE), in particular VLDE, LLDPE, LMDPE, LDPE or HDPE , Polypropylene (PP), Polyester, Polyamide (PA), Polystyrene (PS), Polycarbonate (PC), Plastics containing halogen, in particular Polyvinylchloride (PVC).
11. Polyvinylidene chloride (PVDC) or Polychlorotrifluoroethylene (PCTFE), Poly-Acrylic-Nitrile (PAN), Tetrafluoroethylene / ethylene or a combination of the aforementioned plastics and has a thickness of 8 to 200 μ, preferably 12 to 75 μ.
12. 12. A cover sheet according to any of claims 1 to 11, wherein the aluminum foil of the C layer has a thickness of 7 to 60 μ? T ?, preferably 9 to 30 μ.
13. 13. A bubble-shaped package for packaging pharmaceutical and medical products containing (a) a base sheet in which bubbles are formed to define bags therein; and (b) a cover sheet according to any of claims 1 to 12, which can be sealed to the base sheet except in the region of the bubbles and mechanically peelable from the base sheet.
14. 14. A bubble-shaped medicine package according to claim 13 comprising (a) a base sheet in which bubbles are formed to define pockets therein to contain the inhalable medicament; (b) a cover sheet that can be sealed to the base sheet except in the region of the bubbles and mechanically peelable from the base sheet to allow release of said inhalable medicament, wherein said cover sheet has a laminate structure comprising at least the following successive layers: (Layer A) an outer cover sheet layer of cellulose material; attached to (Layer B) a first layer of intermediate cover sheet of layer B material; attached directly or indirectly to (Layer C) a layer of aluminum foil cover sheet; attached directly or indirectly to (Layer D) a layer of internal thermoadhesive cover sheet.
15. 15. A drug package according to claim 14 in the form of an elongated bubble strip.
16. 16. A drug package according to any of claims 14 or 15, wherein the first intermediate cover sheet layer comprises woven polyamide.
17. 17. A drug package according to claim 16, wherein the woven polyamide layer has a thickness of 50 to 100 microns.
18. 18. A drug package according to claim 17, wherein the bonding of the woven polyamide layer to its adjacent layers is by means of adhesive lamination.
19. 19. A drug package according to claim 17, wherein the bonding of the woven polyamide layer to its adjacent layers is by means of extrusion lamination.
20. 20. A drug package according to any of claims 14 or 15, wherein the first intermediate cover sheet layer comprises spun PET.
21. 21. A package for drug according to claim 20, wherein the spun PET has a weight of 10 to 250 g / m2, particularly 20 to 60 g / m2.
22. 22. A drug package according to claim 21, wherein the bonding of the spun PET layer to its adjacent layers is by means of a lamination technique selected from the group consisting of extrusion lamination, co-lamination, extrusion and lamination by lacquer.
23. 23. A drug package according to claim 22, wherein the bonding of the spun PET layer to its adjacent layers is by extrusion lamination of polyethylene (PE).
24. 24. A drug package according to any of claims 14 or 15, wherein the first intermediate cover sheet layer comprises spun HDPE.
25. 25. A drug package according to claim 24, wherein the spun HDPE has a weight of 10 to 80 g / m2, particularly 20 to 60 g / m2.
26. 26. A drug package according to any of claims 24 or 25, wherein the bonding of the HDPE layer spun to its adjacent layers is by means of extrusion lamination.
27. 27. A package for drug according to claim 26, wherein the bonding of the HDPE layer spun to its adjacent layers is by means of extrusion of polyethylene (PE).
28. 28. A drug package according to any of claims 14 or 15, wherein the first intermediate cover sheet layer comprises cross-laminated HDPE.
29. 29. A drug package according to claim 28, wherein said cross-laminated HDPE comprises at least two HDPE films cross-laminated to each other at a cross lamination angle of 30 to 60 °, particularly 45 °.
30. 30. A package for drug according to any of claims 28 or 29, wherein the layer of Cross-laminated HDPE has a thickness of 30 to 100 microns, particularly 50 to 80 microns.
31. 31. A drug package according to any of claims 14 or 15, wherein the first intermediate cover sheet layer comprises cross-laminated PET.
32. 32. A drug package according to claim 31, wherein said cross-laminated PET comprises at least two PET films cross-laminated to each other at a cross lamination angle of 30 to 60 °, particularly 45 °.
33. 33. A package for drug according to any of claims 31 or 32, wherein the layer of cross-laminated PET has a thickness of 30 to 100 microns, particularly 50 to 80 microns.
34. 34. A drug package according to any of claims 14 to 33, wherein the outer paper cover sheet layer comprises paper with a grade of 10 to 50 g / m2, particularly 20 to 30 g / m2 .
35. 35. A drug package according to any of claims 14 to 34, wherein the thickness of the aluminum foil cover sheet layer is 10 to 60 microns, particularly 15 to 40 microns.
36. 36. A bubble-shaped medicine package comprising (a) a base sheet in which bubbles are formed to define pockets therein to contain the inhalable medicament; (b) a cover sheet that can be sealed to the base sheet except in the region of the bubbles and mechanically peelable from the base sheet to allow release of said inhalable medicament, wherein said cover sheet has a laminated structure comprising at least the following successive layers: (i) an outer cover sheet layer of cellulose material; attached directly or through a first intermediate layer of polymeric material to (ii) a layer of aluminum foil cover sheet; attached to (iii) a cover sheet layer of internal polymeric material.
37. 37. A drug package according to claim 36 in the form of an elongated bubble strip.
38. 38. A package for drug according to any of claims 36 or 37, wherein said first optional intermediate layer of polymeric material comprises a layer by extrusion of polyethylene (PE) and the inner cover sheet layer of polymeric material comprises a removable coating by co-extrusion.
39. 39. A drug package according to claim 38, wherein the release coextrusion coating cover sheet layer has a weight of about 5 to 50 g / m2, particularly 10 to 30 g / m2. .
40. 40. A drug package according to any of claims 36 or 37, wherein there is no optional first intermediate layer of polymeric material and the inner cover sheet layer of polymeric material comprises a release film.
41. 41. A drug package according to claim 40, wherein said release film is selected from the group consisting of a polyethylene (PE) peelable film, a polyvinyl chloride (PVC) peelable film or a peelable film. polypropylene (PP).
42. 42. A drug package according to any of claims 40 or 41, wherein the release film is particularly suitable for releasably sealing an inner base sheet layer comprising polyvinyl chloride (PVC) or polyethylene (PE). ).
43. 43. A package for drug according to any of claims 40 to 42, wherein the layer of release film has a thickness of 10 to 80 microns, particularly 15 to 50 microns.
44. 44. A package for drug according to any of claims 36 or 37, wherein the first optional intermediate layer of polymeric material comprises poly (ethylene terephthalate) (PET) and the inner cover sheet layer of polymeric material comprises polyvinyl (PVC).
45. 45. A package for a drug according to claim 44, wherein the PET layer has a thickness of 5 to 30 microns, particularly 10 to 25 microns; and the PVC layer has a thickness of 5 to 50 microns, particularly 10 to 40 microns.
46. 46. A package for drug according to any of claims 36 or 37, wherein the first optional intermediate layer of polymeric material comprises spun poly (ethylene terephthalate) (spun PET) and the inner cover sheet layer of polymeric material comprises a film removable.
47. 47. A drug package according to claim 46, wherein said release film is selected from the group consisting of a polyethylene (PE) release film, a polyvinyl chloride (PVC) release film or a release film of polyvinyl chloride (PVC). polypropylene (PP).
48. 48. A drug package according to any of claims 46 or 47, wherein the release film is particularly suitable for releasably sealing an inner base sheet layer comprising polyvinyl chloride (PVC) or polyethylene (PE). ).
49. 49. A drug package according to any of claims 46 to 48, wherein the spun PET layer has a thickness of 10 to 60 microns, particularly 20 to 30 microns; and the release film layer has a thickness of 5 to 50 microns, particularly 10 to 40 microns.
50. 50. A package for drug according to any of claims 36 or 37, wherein the optional first intermediate layer of polymeric material comprises cross-laminated high density polyethylene (HDPE) and the inner cover sheet layer of polymeric material comprises a release film.
51. 51. A drug package according to claim 50, wherein said cross-laminated HDPE comprises at least two HDPE films cross-laminated to each other at a cross lamination angle of 30 to 60 °, particularly 45 °.
52. 52. A package for drug according to any of claims 50 or 51, wherein said layer of cross-laminated HDPE has a thickness of 30 to 100 microns, particularly 50 to 80 microns; and the release film layer has a thickness of 5 to 50 microns, particularly 10 to 40 microns.
53. 53. A drug package according to any of claims 50 to 52, wherein said release film is selected from the group consisting of a polyethylene (PE) release film, a polyvinyl chloride (PVC) release film, or a removable polypropylene (PP) film.
54. 54. A drug package according to any of claims 50 to 53, wherein the release film is particularly suitable for releasably sealing an inner base sheet layer comprising polyvinyl chloride (PVC) or polyethylene (PE). ).
55. 55. A drug package according to any of claims 36 to 54, wherein the joining of the first optional intermediate layer of polymeric material to its adjacent layers is by means of a lamination technique selected from the group consisting of extrusion lamination. , lamination by co-extrusion and lamination by lacquer.
56. 56. A drug package according to any of claims 36 to 55, wherein the layer of the outer cover sheet comprises paper with a grade of 10 to 80 g / m2, particularly 20 to 50 g / m2.
57. 57. A drug package according to any of claims 36 to 56, wherein the thickness of the aluminum foil cover sheet layer is 10 to 60 microns, particularly 15 to 40 microns.
58. 58. A drug package according to any of claims 14 to 57, wherein the base sheet of the present invention comprises (i) a first foil layer of aluminum foil; and (ii) a second base sheet layer of polymeric material with a thickness of 10 to 150 microns.
59. 59. A drug package according to claim 58, wherein the first foil layer of aluminum foil typically has a thickness of 15 to 120 microns, particularly 20 to 90 microns.
60. 60. A package for drug according to any of claims 58 or 59, wherein the second base sheet layer of polymeric material has a thickness of 10 to 120 microns, particularly 15 to 100 microns.
61. 61. A drug package according to any of claims 58 to 60, wherein the second base sheet layer comprises a polymeric material of water vapor permeability of less than 0.6 g / (100 inches2) (24 hours) (one thousand) at 25 ° C.
62. 62. A drug package according to claim 61, wherein the second base sheet layer comprises a material selected from the group consisting of polyvinyl chloride (PVC).; Polypropylene; polyethylene; polyvinylidene chloride (PVDC); polychlorotrifluoroethylene (PCTFE); cyclic olefin copolymer (COC); and cyclic olefin polymer (COP).
63. 63. A drug package according to any of claims 58 to 62, wherein the first foil layer of foil is provided with an outer foil layer of a polymeric material.
64. 64. A package for drug according to claim 63, wherein said outer base sheet layer comprises oriented polyamide (OPA).
65. 65. A drug package according to any of claims 40 to 43, wherein the base sheet has a PE peelable film provided as an inner base sheet layer.
66. 66. A package for drug according to any of claims 44 or 45, wherein the base sheet is provided with an inner base sheet layer comprising heat-adhesive lacquer.
67. 67. A package for drug according to any of claims 14 to 39 and 46 to 54, wherein the base sheet is provided with an inner base sheet layer comprising polyvinyl chloride (PVC).
68. 68. A bubble-type package for drug according to any of claims 14 to 67, wherein one or more of said package bubbles contain inhalable drug in dry powder form.
69. 69. A bubble-type package for a drug according to claim 68, wherein said inhalable drug comprises one or more drug actives selected from the group consisting of anti-inflammatory agents, anticholinergic agents, other β2-adrenoreceptor agonists, anti-infective agents. , and antihistamines, and any mixture thereof.
70. 70. A bubble-type package for a drug according to claim 69, wherein said anti-inflammatory agents are selected from the group consisting of corticosteroids, NSAIDs and any mixture thereof.
71. 71. A bubble type pack for drug according to claim 69, wherein said corticosteroids are selected from the group consisting of methyl prednisolone, prednisolone, dexamethasone, fluticasone propionate, 6a, 9a-difluoro-17a - [( 2-furanylcarbonyl) oxy] -11 ß-h id roxy-16a-methyl-3-oxo-and rosta-1,4-dien-17-carbothioic ester-fluoromethyl ester, 6a, 9a-difluoro-11-hydroxy acid -l 6a-methyl-3-oxo-17a-propionyloxy-androsta-1,4-dien-17p-carbothioic ester S- (2-oxo-tetrahydro-furan-3S-il), esters of beclomethasone (eg the ester 17 -propionate or ester 17,21-dipropionate), budesonide, flunisolide, mometasone esters (eg furoate ester), triamcinolone acetonide, rofleponide, ciclesonide, butyxocort propionate, RPR-106541, and ST-126, and any mixture of the same.
72. 72. A bubble-type package for drug according to claim 69, wherein said NSAIDs are selected from the group consisting of sodium cromoglycate, nedocromil sodium, phosphodiesterase inhibitors (PDE), leukotriene antagonists, synthesis inhibitors of leukotriene, NOS inhibitors, tryptase and elastase inhibitors, beta-2-enetrin antagonists and adenosine receptor agonists or antagonists, cytosine antagonists, cytosine synthesis inhibitors and any mixture thereof.
73. 73. A drug delivery device comprising a housing; and within said housing an elongated bubble-type drug package according to any of claims 68 to 72, wherein said dispensing device includes an internal mechanism for delivering inhalable drug from the bags of the drug package, said mechanism comprises, a) an opening station for receiving a drug package bag; b) releasable means positioned to retain a base sheet and a cover sheet of a bag that has been received in said opening station to detach said base sheet and cover sheet, to open said bag, said removable means include means for directing the cover for removing a cover sheet and a base sheet from a bag that has been received in said opening station; c) an exit, placed in communication with an open bag by which the user can access the drug dose of such open bag; d) addition means for individually indexing the different pouches of the drug package.
74. 74. The use of a drug delivery device according to claim 73 for delivering inhalable drug.
75. 75. A bubble-type package for packaging products including pharmaceutical and medical products, cosmetic products, food and non-food products and for other technical applications, the package comprises (a) a base sheet in which the bubbles are formed to define the bags in it; and (b) a cover sheet according to any of claims 1 to 12, which can be sealed to the base sheet except in the region of the bubbles and can be mechanically released from the base sheet.