Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
  • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches

Definitions

• the present invention relates to application aids for transdermal therapeutic systems, and more particularly to protective covers for transdermal therapeutic systems which facilitate the attachment of the systems to a patient's skin.
• Transdermal therapeutic systems are typically applied to the skin of a patient to administer an active ingredient contained therein.
• the administration takes place by diffusion of the active substance into the skin and via the vessels present therein into the bloodstream of the patient.
• Transdermal therapeutic systems usually include an active agent depot, a drug-impermeable backing layer and a protective film which is removed prior to application of the system.
• matrix systems two basic types of transdermal therapeutic systems are known, matrix systems and reservoir systems.
• matrix systems the active ingredient is contained in a polymer matrix, which is usually formed from a self-adhering pressure-sensitive polymer. The release of active ingredient is controlled by the concentration gradient to the skin.
• reservoir systems the active ingredient is contained in a liquid, semi-solid or solid reservoir, the release of active ingredient being regulated by means of a membrane.
• the protective film of the plaster is first removed before the system is attached to the skin.
• the protective film protrudes beyond the edge of the remaining plaster with some plasters.
• Other transdermal therapeutic systems use a two-part protective film, the abutting edges of which stand up when bending the plaster and can thus be gripped without touching the active substance-containing area of the plaster.
• Embodiments of such a transdermal therapeutic system comprise an active substance depot containing at least one active substance, an application side adapted to be applied to a skin, which is pressure-sensitive at least over part of the area, and a protective film covering the application side, which comprises a first
• Protective film part and a second protective film part comprises, wherein the first protective film part differs in its physical properties from the second protective film part.
• the application page is the side of the transdermal therapeutic system intended for contact with the skin.
• the application side can be made pressure-sensitive over the entire surface, for example by the active substance depot itself being coated over the entire surface with a pressure-sensitive adhesive or with a self-adhesive, or by adhesive bonding over only part of the surface, for example by enclosing the active substance depot in an adhesive ring with the aid of z.
• the back of the drug depot remote from the application side may be covered by a preferably active substance-impermeable backing layer.
• the different physical properties include different surface tensions of the protective film parts on the sides facing the application side, whereby different degrees of adhesion of the protective film parts on the application side is achieved.
• the different physical properties include different thicknesses of the protective film parts, whereby different take-off efficiencies can be easily realized.
• the different physical properties may also include the stiffnesses of the protective films, for example, by certain methods such. As stretching or plasticizer can be adjusted in order to achieve different deduction efficiencies.
• the different physical properties comprise different surface structures of the protective film on at least the sides facing the application side, as a result of which differently sized contact surfaces and, associated therewith, differing adhesive forces are created.
• the surface structure of a protective film part is formed by an embossed structure.
• the surface structure of a protective film part is formed by the roughness of its surface.
• the different physical properties in embodiments expediently include the formation of the protective film parts in different materials, since in this way both different adhesion properties and different withdrawal efficiencies can be achieved.
• the first protective film part and / or the second protective film part may have a coating on the side facing the application side, wherein the coating (s) are designed such that the protective film parts adhere differently to the application side.
• the two protective film parts differ in preferred embodiments in the color of their facing away from the application side surfaces, so that the more easily peelable protective film part is visually easy to identify.
• Figure 1 shows a cross section through a transdermal therapeutic
• FIG. 2 illustrates various embodiments of a transdermal therapeutic system designed according to FIG. 1 in a schematic bottom view
• Figure 3 is a schematic representation of a bottom view of a
• transdermal therapeutic system with improved release peelability, in which protective film parts partially overlap,
• FIG. 4 illustrates the transdermal therapeutic system of FIG. 3 in a schematic cross-sectional representation
• FIG. 5 shows various embodiments of coated protective film parts in schematic perspective illustrations
• FIG. 5 shows various embodiments of coated protective film parts in schematic perspective illustrations
• FIG. 6 shows a schematic representation of a cross section through part of a three-dimensionally structured protective film part.
• the schematic cross-sectional view of FIG. 1 illustrates a transdermal therapeutic system 10 with improved protective-film peelability.
• FIG. 2 shows, in the illustrations a) to f), schematic bottom views of various embodiments of patches 10 with a structure corresponding to FIG.
• the plasters 10 shown in FIGS. 1 and 2 consist of a backing layer 12, which is formed by a film which is impermeable to the active substance.
• the backing layer 12 covers the rear side of the drug depot 1 1 arranged thereunder.
• the drug depot 11 is formed with one of the two protective film parts 14a and 14b
• Protective film 14 covered In order to facilitate removal of the protective film parts 14a and 14b from the active substance depot 11, the two protective film parts, as explained in more detail below, have different physical properties.
• the two protective film parts 14a and 14b adjoin one another directly at one of their edges, so that together they form a closed surface of the width b and the length 1.
• the protective film 14 may also have a different shape from a rectangular shape.
• the two protective film parts 14a and 14b are replaced by the active substance depot 11, and that of the depot of active substance 1 1 and the
• Back layer 12 formed laminate 13 with the freed from the protective film 14 skin-side surface applied to the skin.
• the lateral dimensions of the laminates 13, ie their dimensions transverse to the layer sequence, are always smaller than those of the protective film 14 covering the respective laminate 13, the laminates 13 being arranged completely within the protective film edges are.
• Protective foils 14 thus have an edge area not covered by the laminate 13, at which they can be touched for peeling without the risk of touching an active substance-containing part of the laminate 13.
• first the more easily peelable protective film part is removed and then the laminate 13 is applied to the exposed skin-side area on the application site, the system being held in the area of the other protective film part.
• the second protective film part can then be grasped at the free edge area and stripped off either directly or by bending over the plaster, as a result of which the laminate comes to lie all over the skin.
• FIGS. 3 and 4 schematically illustrate a further embodiment of a transdermal therapeutic system 10 with improved peelability of the protective film 14.
• the two protective film parts partially overlap in this embodiment.
• Such embodiments are preferred in systems 10 where the drug depot 1 1 is prone to cold flow and could exit between shockwave protective foil portions.
• laminates 13 such as protective films 14 of transdermal therapeutic systems 10 are not limited to the embodiments illustrated in FIGS. 1 to 4. Rather, they are subject to the condition that the protective film 14 completely covers the skin-side surface of the laminate 13, according to the intended application of a respective transdermal Therapeutic system freely selectable, so that in addition to the shown round, oval and rectangular shapes in particular also annular, star-shaped or pronounced with wavy edges can be used. Further, laminate 13 and protective film 14 may be the same size so that the protective film does not protrude beyond the edge or edges of the laminate.
• the transdermal therapeutic system 10 can be embodied both as a matrix system and as a reservoir system.
• the agent depot formed by a matrix or a reservoir is covered on one side with an active substance-impermeable backing layer 12, which is also enclosed by it on the side surfaces.
• the application side of the drug depot opposite this side serves to establish contact with the skin of a patient.
• the application side is designed to be pressure-sensitive, which means that the active substance depot itself is pressure-sensitively adhesive, has a self-adhesive layer on the skin side, or is bordered by an adhesive edge.
• the active substance depot 11 When embodied as a matrix system, the active substance depot 11 preferably consists of a matrix containing the active substance based on a self-adhesive. To form the matrix, all suitable for transdermal therapeutic systems suitable materials such.
• B homopolymers and copolymers of (meth) acrylates, polyvinyl ethers, polyisobutylenes, polyisoprene rubber
• Styrene-butadiene copolymers or styrene-butadiene-styrene copolymers and silicones are examples.
• (meth) acrylate copolymers mention may be made, for example, of the copolymers of alkyl acrylates and / or alkyl methacrylates and further unsaturated monomers, such as acrylic acid, methacrylic acid, acrylamide, dimethylacrylamide, dimethylaminoethylacrylamide, acrylonitrile and / or vinyl acetate.
• a self-adhesive matrix system on the skin side with a further pressure-sensitive adhesive layer.
• a covering layer which covers the matrix and is provided with a self-adhesive adhesive on the skin side, usually referred to as overtape, can be used.
• the active ingredient will usually be in a liquid or gel, with the drug reservoir having a membrane on the skin side which controls the delivery of the active ingredient to the skin.
• the skin-side surface of the laminate 13 in reservoir systems is preferably coated with a pressure sensitive adhesive to allow adhesion of the protective film thereto and fixation of the patch on the skin.
• a covering layer which covers the reservoir and is provided with a self-adhesive adhesive on the skin side can also be used here, which encloses the reservoir within an adhesive edge.
• Adhesive adhesives also referred to as pressure-sensitive adhesives, are understood in this document to be adhesives which adhere to them when they come into contact with a material surface.
• the interfacial properties of such an adhesive bond are determined by the interfacial tensions, also referred to as surface tensions, at the interface between the material and pressure-sensitive adhesive surfaces.
• the construction of an adhesive bond requires wetting of the surface of the material by the adhesive, for which the interfacial tension of the adhesive must not be higher than that of the material surface. Only then is the attraction of the adhesive to the material surface higher than to itself, so that it can flow on the material surface.
• the peelability of a protective film applied to a pressure sensitive adhesive is determined by the release force required to peel off the film and the effectiveness with which the release force is applied can be. While the release force required to peel off increases with the adhesive force of the adhesive bond and is thus essentially determined by the wetting of the protective film by the adhesive, the effectiveness of applying the release force is determined by the physical properties of the protective film which depend on the reaction of peeling off the protective film applied tensile force act in a release force and thus are different from surface tensions. Essential for the implementation of a tensile force in a release force are primarily flexibility and elasticity of the protective film material.
• a protective film part is usually gripped at one of its edge regions and the gripped region is subsequently pulled over the region of the laminate covered by the gripped protective film part.
• the bending radius of the protective film part forming in this case is greater, the stiffer the protective film part is, or the smaller, the more flexible the protective film part is. Flexibility here is understood as the property of a material to bend as a result of a force acting perpendicularly to one of its surfaces. The smaller the bending radius when the protective film part is pulled off, the greater is the force component oriented perpendicular to the interface between the adhesive and the protective film at the transition from the area of the protective film part which has already been detached and still adheres to the adhesive.
• Embodiments of a transdermal therapeutic system with a protective film formed by protective film parts of different peelability therefore have at least two protective film parts of different stiffness, or, expressed differently, different degrees of flexibility.
• One possibility for the formation of protective film parts of different flexibility or rigidity consists in the formation of the two protective film parts with different materials.
• Suitable protective film materials are, for example, polyethylenes, such as HDPE, polypropylenes, polyesters, polysiloxanes, polyethylene terephthalates, polyvinyl chlorides or polyurethanes, optionally in the form of laminates.
• Suitable protective films are, for example, under the trade designation Scotchpak from 3M Company (as Scotchpak ® 1020, 1022, 9736, 9742, 9744, 9755), by the company Siliconature z.
• the flexibility and stiffness of a protective film part can also be influenced by its thickness or material thickness, so that in embodiments the film thickness of one of the protective film parts 14a differs from that of another of the protective film parts 14b.
• the protective film parts can differ both in the film material and in the film thickness.
• the material and thickness should be selected so that the protective film parts do not have significant elasticity, that is, they do not noticeably stretch in the forces required to detach.
• the thickness can be suitably selected as a function of the properties of the material, with the order of magnitude of, for example, the range of 10 to 70 ⁇ for a first protective film part and the range of 75 to 150 ⁇ for a second protective film part.
• the second factor that is important for the peelability of a protective film part 14a or 14b is its adhesive force on the adhesive surface of a transdermal therapeutic system 10. This is determined by the surface tension of the surface of the adhesive surface contacting the adhesive surface Protective film part influenced. In embodiments of transdermal therapeutic systems 10, the protective film parts 14a and 14b therefore differ in surface tension at their contact surface intended for application to a laminate 13.
• the surface tensions of the contact surfaces can be reduced by silicone, fluoropolymer or fluorosilicone coating, the choice of the coating 15 being matched to the adhesive used on the application or skin side of the laminate.
• the perspective sectional view of FIG. 5a illustrates a protective film part 14a or 14b, which is formed by a film material 14 # coated over the entire surface of the contact surface.
• the protective film part with the lower surface tension at the contact surface has a lower adhesion to the laminate 13 and therefore requires a smaller release force for detachment.
• the coating with the lower surface tension does not have to cover the entire laminate-side surface of a respective protective film part.
• a coating of the contact surface of the protective film part, d. H. the surface area used to cover the pressure-sensitive adhesive can also be limited to a partial area of the contact area, wherein this partial area is formed by the area to be detached first when the protective film part is removed.
• At least one of the two protective film parts 14a or 14b has two coatings with different surface tensions, wherein one of the coatings covers the laminate-side surface of the respective protective film part over part of its surface in the form of a pattern.
• This patterned coating 16 can, as shown schematically in FIG. 5b, be arranged on a previously applied coating 15 over the entire surface, or Also, as illustrated in FIG. 5c, cover uncovered surface areas of the protective film base material from a likewise patterned first coating 15. In the latter case, the patterns of the two coatings 15 and 16 instead of overlapping as illustrated can also be designed to be complementary.
• the wettability of the laminate-side surface of one of the protective film parts is reduced by bringing the surface into contact with a self-adhesive adhesive before it is applied to the laminate 13 and then releasing it again therefrom.
• peeling adhesive residues remain on the protective film part and determine at these points the local surface tension of the protective film part.
• the adhesive force of the protective film part on the skin side of the laminate 13 can be reduced.
• This method can also be used for coated protective film parts 14a or 14b, the adhesive residues filling in particular pores in the coating.
• the adhesion of protective film parts 14a and 14b to a laminate 13 is also determined by the ratio of contact area to coverage area on the contact side of a protective film part. Under contact surface is in this case wetted by the adhesive surface of a
• FIG. 6 An example of a correspondingly executed protective film 14 is shown in the cross-sectional representation of FIG. 6. shown schematically.
• the protective film parts 14a and 14b have recesses 14 *, the z. B. are formed by embossing. As a rule, the recesses are not filled with the pressure-sensitive adhesive of a laminate 13 covered by the protective film, and the bottom of the recesses is thus not wetted by the adhesive. If both protective film parts 14a and 14b have a three-dimensional structuring, the contact surface 14 "provided for contact with the self-adhesive adhesive is less in one of the two protective film parts than in the other.
• Protective film part 14a and 14b are achieved. If the surface is sufficiently rough, contact with a not-too-cold-flow may occur
• Protective films 14 with more than two protective film parts may also be limited to a partial region of the contact surface, as long as this partial region forms the region of the protective film part which is first peeled off when a laminate 13 is removed.
• Known test methods can be used to determine the peelability of the protective film parts. For example, an adhesion measurement according to a corresponding DIN specification such. B. DIN EN 1939 be made.
• the separation force can, for.
• a FINAT (Federation international des solids et transformateur d'ad hocifs et thermocollants sur papiers et herb supports) test such as FTM 3 and 4 can be used. Since the improvement of peelability of the protective film is achieved primarily by the relative differences in the peelability of the protective film parts and not so much by the separation force to be applied absolutely, another conventional method for determining adhesion or release force can be used, provided the measurement for both protective film parts according to the same method.
• this protective film part is preferably color-contrasted from the other protective film parts, for example, by a special coloration of its visible, generally the application side of the laminate 13 facing away, surface. For a different coloration, a colored or printed film material can be used.
• the protective film part to be peeled off first can also be identified by a corresponding imprint or gripping lug.
• Protective film 14 is formed by two protective film parts 14a and 14b with different physical properties.
• transdermal therapeutic systems were prepared containing a matrix of a pressure-sensitive adhesive acrylate-vinyl acetate copolymer.
• Each TTS was equipped with a combination of two different surface-coated protective film parts 14a and 14b, respectively.
• a first protective film part (14a) with the coated surface was applied to a part of the adhesive surface of the matrix.
• the second protective film part (14b) was applied overlapping to the first protective film part (14a) on the uncovered, free part of the adhesive surface of the matrix.
• the coated side of the second protective film part (14b) showed the adhesive surface of the matrix.
• the first protective film part was a silicone-coated polyester film having a thickness of 50 ⁇ m, which is commercially available from Loparex Inc. under the name FL2000 / 50, or a fluoropolymer-coated polyester film having a thickness of 74 ⁇ m, which from 3M under the designation Scotchpak TM 9755 in the Trade is.
• the second protective film part was a silicone-coated polyester film with a thickness of 100 ⁇ , which is marketed by the company Loparex Inc. under the name FL2000 / 100 ⁇ , or a fluoropolymer-coated polyester film with a thickness of 74 ⁇ used by the company 3M under the name Scotchpak TM 1020 is commercially available.
• the peel force of the individual protective film parts (14a, 14b) was determined by means of a tensile tester (EZ-Test, Shimadzu, Germany), the peel force being the force that is necessary for the protective film part of the pressure-sensitive adhesive matrix to solve.
• the specific take-off angle in the present case is 90 °
• the take-off speed is 300 ⁇ 30 mm / min.
• the specimen was fixed on the smooth surface of the sample block so that the
• Scotchpak TM 1020 0.306 It can be seen from the table that with the same coating, but different thickness of the protective film material, different take-off forces result. This also applies to protective films of the same thickness but different surface coating.
• the invention described enables a transdermal therapeutic system with improved peelability of the protective film, which also allows persons with limited motor skills to attach the patch to a skin easily and without the risk of accidental contamination of body parts or objects.

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• 2011
  • 2011-08-03 DE DE102011080390A patent/DE102011080390B3/de active Active
• 2012
  • 2012-08-03 EP EP12745829.7A patent/EP2739273A1/de not_active Withdrawn
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