US20150150827A1 - Multi-layered transdermal system with triazine uv absorber - Google Patents
Multi-layered transdermal system with triazine uv absorber Download PDFInfo
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- US20150150827A1 US20150150827A1 US14/607,861 US201514607861A US2015150827A1 US 20150150827 A1 US20150150827 A1 US 20150150827A1 US 201514607861 A US201514607861 A US 201514607861A US 2015150827 A1 US2015150827 A1 US 2015150827A1
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- transdermal therapeutic
- therapeutic system
- solid transdermal
- absorber
- layer
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- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
-
- 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
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
-
- 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
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- 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
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
Definitions
- the invention is a solid transdermal therapeutic system with UV absorber.
- the UV-stable transdermal therapeutic system is particularly designed for photosensitive active pharmaceutical ingredients. It comprises a backing layer 1 , of at least one active ingredient-containing matrix 2 , and of a detachable protective film 3 . However an adhesive layer 4 and a separating layer 5 can optionally be introduced between the backing layer 1 and the active ingredient-containing matrix 2 . At least one hydroxyphenyltriazine acting as UV absorber can be embedded in the backing layer 1 , in the active ingredient-containing matrix 2 , or in the adhesive layer 4 .
- Transdermal therapeutic systems which contain a gestagen and/or an estrogen, are suitable for controlling fertility.
- TTS transdermal therapeutic systems
- WO-A1-00/56289 describes a method for protecting therapeutic preparations, systems or their constituents, the intention being to achieve in each case specific protection from degradation by harmful factors, such as atmospheric oxygen, water, and/or light.
- Photo-protective substances which absorb or reflect electromagnetic waves, are used, employing respectively absorbents or reflectants whose absorption or reflection spectrum covers the wave-length range responsible for the instability of the photosensitive substance or its constituents.
- Colored plastic films are used, inter alia, in this case as covering film, indicated by example of the 1,4-dihydopyridine derivative lacidipine.
- WO-A2-02/34200 further discloses transdermal therapeutic systems (TTS), which consist of an active ingredient-containing polymer matrix and of a backing layer.
- TTS transdermal therapeutic systems
- the polymer matrix and the backing layer are firmly connected or form a laminate. Both the polymer matrix and the backing layer comprise a colorless system, which absorbs in the UV range but has no intrinsic pharmacological effect.
- EP-A1-1452173 describes transdermal therapeutic systems, which consist of a backing layer, of at least one active ingredient-containing matrix and optionally of a detachable film and comprises a UV absorber. At least one UV absorber-containing adhesive layer is provided between the backing layer and the active ingredient-containing matrix furthest away from the surface of the skin.
- the UV absorber can be p-aminobenzoic acid, an aminobenzoic acid derivative, preferably 2-ethylhexyl 4-dimethyl-amino-benzoate and/or polyethoxyethyl 4-bis-(polyethoxyl)amino-benzoate, cinnamic acid, a cinnamic acid derivative, preferably isoamyl 4-methoxycinnamate or 2-ethylhexyl 4-methoxycinnamate, 3-benzylidenebornan-2-one, a benzylidene bornan-2-one derivative, preferably 3-(4′-methylbenzylindenebornan-2-one, 3-(4-sulphone)-benzylideneborn
- a solid transdermal therapeutic system with a UV absorber
- the UV-stable TTS comprises a sequence of at least three layers, namely a backing layer 1 , at least one active ingredient-containing matrix 2 , and a detachable protective film 3 .
- an adhesive layer 4 and a separating layer 5 can be introduced between the backing layer 1 and the at least one active ingredient-containing matrix 2 .
- the UV absorber comprises at least one hydroxyphenyltriazine compound and the UV absorber is embedded in the backing layer 1 , in the active ingredient-containing matrix 2 , or in the adhesive layer 4 .
- FIG. 1 is a graphical illustration showing the percentage of photosensitive active ingredient remaining in a transdermal therapeutic system according to the invention with photo-protective features and the percentage of photosensitive active ingredient remaining in a comparative transdermal therapeutic system;
- FIGS. 2 to 4 are respective diagrammatic cross-sectional views through various embodiments of the transdermal therapeutic systems according to the invention.
- the UV absorber is 2,4-bis-([4-(2′-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine.
- the weight per unit area of the matrix 2 is from 30 to 150 g/m 2 .
- a weight per unit area of from 50 to 120 g/m 2 is preferred, and of 100 g/m 2 is particularly preferred.
- the weight per unit area of the adhesive layer 4 is from 5 to 50 g/m 2 .
- a weight per unit area of from 20 to 30 g/m 2 is preferred.
- the UV absorber can be present according to the invention in the adhesive layer 4 in a concentration of from 0.5 to 5% (m/m) in dissolved form. In this connection, a concentration of from 1.0 to 4.0% is preferred, and of from 1.5 to 3.0% is particularly preferred.
- matrix 2 and/or the adhesive layer 4 in the solid transdermal therapeutic system can be designed according to the invention to be self-adhesive and can consist substantially of polymers, which are selected from the group consisting of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene-isoprene block polymer and polyisoprene.
- Preferred embodiments of the solid transdermal therapeutic systems according to the invention have a separating layer thickness of from 4 to 23 ⁇ m. In this connection, a layer thickness of from 4 to 10 ⁇ m is preferred.
- the separating layer 5 is preferably impermeable to the active ingredient and impermeable to the UV absorber.
- the separating layer 5 can consist of a barrier polymer. Preference is given in this connection to polyethylene terephthalate, polyacrylonitrile, polyvinyl chloride, polyvinylidene chloride, or its copolymers or co-laminates.
- the backing layer 1 is permeable to active ingredient and consists of polypropylene, of polyethylene, of polyurethane, of ethylene-vinyl acetate copolymer, or of a multilayer composite of these materials with one another or with other materials.
- the UV absorber(s) in the solid transdermal therapeutic system according to the invention can be colorless or yellowish.
- solid transdermal therapeutic system according to the invention it is furthermore possible for the solid transdermal therapeutic system according to the invention to be transparent or slightly opaque.
- the active ingredient in the solid transdermal therapeutic system according to the invention can be at least one hormone.
- the active pharmaceutical ingredient according to the invention can be a progestogen, preferably gestodene or levonorgestrol. Furthermore an estrogen, preferably ethinyl estradiol, can be added to the progestogen in the solid transdermal therapeutic system according to the invention.
- the solid transdermal therapeutic system can also be used to control fertility.
- the solid transdermal therapeutic system prefferably equipped without a membrane controlling active ingredient release.
- the transdermal therapeutic system according to the invention has the following advantages compared with conventional systems with photosensitive active ingredient content.
- Formulation 2 comprises an adhesive layer 4 and a separating layer 5 , and the adhesive layer comprises 2.5% by weight of a UV-absorbing substance from the hydroxyphenyltriazine compounds.
- Formulation 1 has no adhesive layer and no separating layer.
- Formulation 1 serves as comparative formulation. Both formulations comprise an active ingredient-containing matrix 2 with a photosensitive progestogen and are equipped with a backing layer 1 of polyethylene, resulting in a TTS in each case.
- Formulation 2 has the following composition:
- both formulations were irradiated with light having a UV spectrum of 300-800 nm for a period of up to 34 h.
- the radiation source used was a xenon lamp.
- a filter system (type: Suprax® filter) was placed between the radiation source and the samples to be irradiated in order to simulate irradiation under realistic conditions of use of the TTS. The active ingredient content in the TTS after irradiation was then determined.
- FIG. 1 reveals that the TTS of formulation 2, which comprised an adhesive layer with UV-absorbing substance and a separating layer, still comprised about 95% of the originally employed amount of the photosensitive active ingredient after irradiation for 34 h, whereas the TTS of formulation 1 comprised only about 3% of the originally employed amount of the photosensitive active ingredient after irradiation.
- the system according to the invention has improved protection from the sun under realistic conditions-of-use, since the UV-protective effect of the system according to the invention (formulation 2) was considerably greater than that of the comparative system (formulation 1).
- the formulations of example 2 have a photosensitive active ingredient from the progestogens, and in each case an adhesive layer and separating layer.
- the separating layer in each of these formulations consists of polyethylene terephthalate (Hostaphan® 1 from Mitsubishi Polyester, Wiesbaden).
- Each formulation has the following composition:
- the formulations of example 3 have a photosensitive active ingredient from the progestogens, and in each case two adhesive layers and separating layers.
- the separating layers in each case consist of polyethylene terephthalate (Hostaphan® 1 from Mitsubishi Polyester, Wiesbaden). These formulations each have the following composition:
- the formulations of example 4 have a photosensitive active ingredient from the progestogens, and in each case at least one adhesive layer and separating layer.
- the active ingredient-containing matrix is embodied analogous to examples 1 to 3 and the adhesive layer comprises a poly-isobutylene-based adhesive and has the compositions mentioned below.
- the formulations of examples 13 to 21 have a photosensitive active ingredient from the progestogens, and in each case at least one adhesive layer and separating layer.
- the active ingredient-containing matrix is embodied analogously to examples 1 to 3, and the adhesive layer comprises a polyacrylate-based adhesive and has the compositions mentioned below.
- Example adhesive layer 13 Composition of the Example adhesive layer 13 14 15 16 17 18 19 20 21 Tinosorb ® S [%] 2 2 2 3 3 3 4 4 4 Polyacrylate-based 98 98 98 97 97 96 96 96 adhesive [%] Weight per unit area [g/m 2 ] 20 30 50 20 30 50 20 30 50 20 30 50;
Abstract
Description
- The invention described and claimed hereinbelow is also described in U.S. Provisional Patent Application 60/676,788, filed May 2, 2005, and also in European Patent Application No. 05009579.3, also filed May 2, 2005. The aforesaid US Provisional Patent Application, whose subject matter is incorporated here by reference, provides the basis for a claim of priority of invention under 35 U.S.C. 119 (e).
- The invention is a solid transdermal therapeutic system with UV absorber. The UV-stable transdermal therapeutic system (TTS) is particularly designed for photosensitive active pharmaceutical ingredients. It comprises a
backing layer 1, of at least one active ingredient-containingmatrix 2, and of a detachableprotective film 3. However anadhesive layer 4 and a separatinglayer 5 can optionally be introduced between thebacking layer 1 and the active ingredient-containingmatrix 2. At least one hydroxyphenyltriazine acting as UV absorber can be embedded in thebacking layer 1, in the active ingredient-containingmatrix 2, or in theadhesive layer 4. - Transdermal therapeutic systems, which contain a gestagen and/or an estrogen, are suitable for controlling fertility.
- Attempts to employ photosensitive active ingredients, which absorb UV-A and UV-B rays, customarily used in sun creams, are known, as described by Briscart & Plaizier-Vercammen (Proc. 2nd World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, APGI/APV, 1998, 1231-1232).
- The patent literature further discloses the protection of transdermal therapeutic systems (TTS) provided with photosensitive active ingredients by visually conspicuous aluminized or lacquered covering films as backing layers of the TTS.
- WO-A1-00/56289 describes a method for protecting therapeutic preparations, systems or their constituents, the intention being to achieve in each case specific protection from degradation by harmful factors, such as atmospheric oxygen, water, and/or light. Photo-protective substances, which absorb or reflect electromagnetic waves, are used, employing respectively absorbents or reflectants whose absorption or reflection spectrum covers the wave-length range responsible for the instability of the photosensitive substance or its constituents. Colored plastic films are used, inter alia, in this case as covering film, indicated by example of the 1,4-dihydopyridine derivative lacidipine.
- The coloring of highly flexible plastic films proves to be difficult and does not provide reliable photo-protection owing to the frequently occurring fissures in the colored layer of the plastic film.
- WO-A2-02/34200 further discloses transdermal therapeutic systems (TTS), which consist of an active ingredient-containing polymer matrix and of a backing layer. The polymer matrix and the backing layer are firmly connected or form a laminate. Both the polymer matrix and the backing layer comprise a colorless system, which absorbs in the UV range but has no intrinsic pharmacological effect. EP-A1-1452173 describes transdermal therapeutic systems, which consist of a backing layer, of at least one active ingredient-containing matrix and optionally of a detachable film and comprises a UV absorber. At least one UV absorber-containing adhesive layer is provided between the backing layer and the active ingredient-containing matrix furthest away from the surface of the skin. In addition, at least one separating layer, which is impermeable to active ingredient and impermeable to the UV absorber, is present between the adhesive layer containing the UV absorber and the active ingredient-containing matrix, which is furthest away from the surface of the skin. The UV absorber can be p-aminobenzoic acid, an aminobenzoic acid derivative, preferably 2-ethylhexyl 4-dimethyl-amino-benzoate and/or polyethoxyethyl 4-bis-(polyethoxyl)amino-benzoate, cinnamic acid, a cinnamic acid derivative, preferably isoamyl 4-methoxycinnamate or 2-ethylhexyl 4-methoxycinnamate, 3-benzylidenebornan-2-one, a benzylidene bornan-2-one derivative, preferably 3-(4′-methylbenzylindenebornan-2-one, 3-(4-sulphone)-benzylidenebornan-2-one, or 3-(4′-trimethylammonium)-benzylidenebornan-2-one methylsulphate, salicylic acid derivative, preferably 4-isopropylbenzyl salicylate, 2-ethylhexyl salicylate, or 3,3,3-trimethylcyclohexyl salicylate, a benzotriazole, preferably 2-(5-chloro-2H-benzotriazol-2-yl) -6-(1,1-dimethylethyl)-4-methylphenol, 3-imidazol-4-yl-acrylic acid, 3-imidazol-4-yl-3-imidazol-4-yl-acrylic ester, 2-phenylene benzimidazole-5-sulphonic acid, or its K, Na and triethanolamine (=TEA) salt, 2-cyano-3,3-diphenylacrylic acid, terephthaloylidene-dicamphorsulphonic acid, butylmethoxy-dibenzoylmethane, benzophenone, or a benzophenone derivative, preferably benzophenone-3 or benzophenone-4.
- The known solutions have the disadvantage
-
- that the protective effect produced by the added UV absorber for the active ingredient is incomplete,
- that owing to the incomplete protective effect in some cases higher concentrations of UV absorbers must be employed, which may have adverse effects on the compatibility of the TTS with skin.
- It is therefore an object of the invention to provide a pharmaceutical preparation of the above-described kind with a UV absorber, which is provided with a photosensitive active ingredient, which is to be transdermally administered, and which ensures an increased protective effect for the active ingredient while using a minimum UV absorber concentration, so that the aforementioned disadvantages are avoided.
- This object is achieved according to the invention by a solid transdermal therapeutic system (TTS) with a UV absorber, wherein the UV-stable TTS comprises a sequence of at least three layers, namely a
backing layer 1, at least one active ingredient-containingmatrix 2, and a detachableprotective film 3. Optionally anadhesive layer 4 and a separatinglayer 5 can be introduced between thebacking layer 1 and the at least one active ingredient-containingmatrix 2. In the transdermal therapeutic system according to the invention the UV absorber comprises at least one hydroxyphenyltriazine compound and the UV absorber is embedded in thebacking layer 1, in the active ingredient-containingmatrix 2, or in theadhesive layer 4. - The objects, features and advantages of the invention will now be illustrated in more detail with the aid of the following detailed description and examples of the invention, with reference to the accompanying figures, in which:
-
FIG. 1 is a graphical illustration showing the percentage of photosensitive active ingredient remaining in a transdermal therapeutic system according to the invention with photo-protective features and the percentage of photosensitive active ingredient remaining in a comparative transdermal therapeutic system; and -
FIGS. 2 to 4 are respective diagrammatic cross-sectional views through various embodiments of the transdermal therapeutic systems according to the invention. - In a preferred embodiment according to the invention the UV absorber is 2,4-bis-([4-(2′-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine.
- In various embodiments of the transdermal therapeutic systems according the weight per unit area of the
matrix 2 is from 30 to 150 g/m2. In this connection, a weight per unit area of from 50 to 120 g/m2 is preferred, and of 100 g/m2 is particularly preferred. - Similarly in various embodiments of the solid transdermal therapeutic system according to the invention the weight per unit area of the
adhesive layer 4 is from 5 to 50 g/m2. In this connection, a weight per unit area of from 20 to 30 g/m2 is preferred. - The UV absorber can be present according to the invention in the
adhesive layer 4 in a concentration of from 0.5 to 5% (m/m) in dissolved form. In this connection, a concentration of from 1.0 to 4.0% is preferred, and of from 1.5 to 3.0% is particularly preferred. - Furthermore the
matrix 2 and/or theadhesive layer 4 in the solid transdermal therapeutic system can be designed according to the invention to be self-adhesive and can consist substantially of polymers, which are selected from the group consisting of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene-isoprene block polymer and polyisoprene. - Preferred embodiments of the solid transdermal therapeutic systems according to the invention have a separating layer thickness of from 4 to 23 μm. In this connection, a layer thickness of from 4 to 10 μm is preferred.
- In the solid transdermal therapeutic systems according to the invention the separating
layer 5 is preferably impermeable to the active ingredient and impermeable to the UV absorber. - In preferred embodiments of the invention the separating
layer 5 can consist of a barrier polymer. Preference is given in this connection to polyethylene terephthalate, polyacrylonitrile, polyvinyl chloride, polyvinylidene chloride, or its copolymers or co-laminates. - In preferred embodiments of the solid transdermal therapeutic system according to the invention the
backing layer 1 is permeable to active ingredient and consists of polypropylene, of polyethylene, of polyurethane, of ethylene-vinyl acetate copolymer, or of a multilayer composite of these materials with one another or with other materials. - The UV absorber(s) in the solid transdermal therapeutic system according to the invention can be colorless or yellowish.
- It is furthermore possible for the solid transdermal therapeutic system according to the invention to be transparent or slightly opaque.
- The active ingredient in the solid transdermal therapeutic system according to the invention can be at least one hormone.
- The active pharmaceutical ingredient according to the invention can be a progestogen, preferably gestodene or levonorgestrol. Furthermore an estrogen, preferably ethinyl estradiol, can be added to the progestogen in the solid transdermal therapeutic system according to the invention.
- According to the invention the solid transdermal therapeutic system can also be used to control fertility.
- It is also possible according to the invention for the solid transdermal therapeutic system to be equipped without a membrane controlling active ingredient release.
- The transdermal therapeutic system according to the invention has the following advantages compared with conventional systems with photosensitive active ingredient content.
-
- The protective effect provided by the hydroxyphenyltriazine compounds acting as UV absorber is enhanced.
- The concentration of the hydroxyphenyitriazine compounds acting as UV absorber, which is necessary to achieve a protective effect is reduced.
- It is thus possible in particular to avoid or reduce the risk of possible skin irritation.
- The invention is further illustrated and explained by the following examples.
- Two formulations (1 and 2) of a photosensitive active ingredient from the progestogens were prepared.
Formulation 2 comprises anadhesive layer 4 and a separatinglayer 5, and the adhesive layer comprises 2.5% by weight of a UV-absorbing substance from the hydroxyphenyltriazine compounds.Formulation 1 has no adhesive layer and no separating layer.Formulation 1 serves as comparative formulation. Both formulations comprise an active ingredient-containingmatrix 2 with a photosensitive progestogen and are equipped with abacking layer 1 of polyethylene, resulting in a TTS in each case.Formulation 2 has the following composition: -
- 1. Active ingredient-containing matrix:
- 1.9% progestogen
- 98.1% polyisobutylene-based adhesive;
- 2. Adhesive layer:
- 3% Tinosorb® S
- 97% polyisobutylene-based adhesive.
Tinosorb® S (from Ciba, Lampertheim) is a UV absorber of the hydroxyphenyltriazine class.
- 1. Active ingredient-containing matrix:
- To investigate the photo-protective effect, both formulations were irradiated with light having a UV spectrum of 300-800 nm for a period of up to 34 h. The radiation source used was a xenon lamp. A filter system (type: Suprax® filter) was placed between the radiation source and the samples to be irradiated in order to simulate irradiation under realistic conditions of use of the TTS. The active ingredient content in the TTS after irradiation was then determined.
-
FIG. 1 reveals that the TTS offormulation 2, which comprised an adhesive layer with UV-absorbing substance and a separating layer, still comprised about 95% of the originally employed amount of the photosensitive active ingredient after irradiation for 34 h, whereas the TTS offormulation 1 comprised only about 3% of the originally employed amount of the photosensitive active ingredient after irradiation. - The system according to the invention has improved protection from the sun under realistic conditions-of-use, since the UV-protective effect of the system according to the invention (formulation 2) was considerably greater than that of the comparative system (formulation 1).
- The formulations of example 2 have a photosensitive active ingredient from the progestogens, and in each case an adhesive layer and separating layer. The separating layer in each of these formulations consists of polyethylene terephthalate (Hostaphan®1 from Mitsubishi Polyester, Wiesbaden). Each formulation has the following composition:
- 1. Active ingredient-containing matrix
- 1.9% progestogen
- 98.1% polyisobutylene-based adhesive;
- 2.
Adhesive layer 1 and 2:- 2.5% Tinosorb® S
- 97.5% polyacrylate-based adhesive.
- The formulations of example 3 have a photosensitive active ingredient from the progestogens, and in each case two adhesive layers and separating layers. The separating layers in each case consist of polyethylene terephthalate (Hostaphan®1 from Mitsubishi Polyester, Wiesbaden). These formulations each have the following composition:
- 1. Active ingredient-containing matrix:
- 1.9% progestogen
- 98.1% polyisobutylene-based adhesive;
- 2.
Adhesive layer 1 and 2:- 3% Tinuvin®400
- 97% polyacrylate-based adhesive.
Tinuvin®400 (from CIBA, Lampertheim) is a UV absorber of the hydroxyphenyltriazine class.
- The formulations of example 4 have a photosensitive active ingredient from the progestogens, and in each case at least one adhesive layer and separating layer. In these formulations in which the active ingredient-containing matrix is embodied analogous to examples 1 to 3 and the adhesive layer comprises a poly-isobutylene-based adhesive and has the compositions mentioned below.
-
Composition of the adhesive Example layer 4 5 6 7 8 9 10 11 12 Tinosorb ® S [%] 2 2 2 3 3 3 4 4 4 Polyisobutylene-based 98 98 98 97 97 97 96 96 96 adhesive [%] Weight per unit area [g/m2] 20 30 50 20 30 50 20 30 50 - The formulations of examples 13 to 21 have a photosensitive active ingredient from the progestogens, and in each case at least one adhesive layer and separating layer. The active ingredient-containing matrix is embodied analogously to examples 1 to 3, and the adhesive layer comprises a polyacrylate-based adhesive and has the compositions mentioned below.
-
Composition of the Example adhesive layer 13 14 15 16 17 18 19 20 21 Tinosorb ® S [%] 2 2 2 3 3 3 4 4 4 Polyacrylate-based 98 98 98 97 97 97 96 96 96 adhesive [%] Weight per unit area [g/m2] 20 30 50 20 30 50 20 30 50 - While the invention has been illustrated and described as embodied in a solid transdermal therapeutic system with UV absorber, it is not intended to be limited to the details shown, since various modifications and changes may be made without departing in any way from the spirit of the present invention.
- Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention.
Claims (40)
Priority Applications (1)
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US14/607,861 US20150150827A1 (en) | 2005-05-02 | 2015-01-28 | Multi-layered transdermal system with triazine uv absorber |
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EP05009579A EP1719504A1 (en) | 2005-05-02 | 2005-05-02 | Solid transdermal therapeutic system with UV-absorber |
US11/416,148 US8962013B2 (en) | 2005-05-02 | 2006-05-02 | Multi-layered transdermal system with triazine UV absorber |
US14/607,861 US20150150827A1 (en) | 2005-05-02 | 2015-01-28 | Multi-layered transdermal system with triazine uv absorber |
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US11/416,148 Division US8962013B2 (en) | 2005-05-02 | 2006-05-02 | Multi-layered transdermal system with triazine UV absorber |
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US20150150827A1 true US20150150827A1 (en) | 2015-06-04 |
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US14/607,861 Abandoned US20150150827A1 (en) | 2005-05-02 | 2015-01-28 | Multi-layered transdermal system with triazine uv absorber |
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US11/416,148 Active 2029-06-19 US8962013B2 (en) | 2005-05-02 | 2006-05-02 | Multi-layered transdermal system with triazine UV absorber |
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