EP1233764A1 - Dispositif transdermique comprenant un reservoir et une matrice contenant le meme principe actif - Google Patents
Dispositif transdermique comprenant un reservoir et une matrice contenant le meme principe actifInfo
- Publication number
- EP1233764A1 EP1233764A1 EP00985366A EP00985366A EP1233764A1 EP 1233764 A1 EP1233764 A1 EP 1233764A1 EP 00985366 A EP00985366 A EP 00985366A EP 00985366 A EP00985366 A EP 00985366A EP 1233764 A1 EP1233764 A1 EP 1233764A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- type
- reservoir
- compartment
- active principle
- matrix
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
-
- 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
- A61K31/568—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 positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
- A61K9/7092—Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
Definitions
- Transdermal device comprising a reservoir and a matrix containing the same active ingredient.
- the subject of the invention is a self-adhesive device intended for the transdermal administration of an active principle, comprising a double reservoir formed by at least one central compartment and at least one peripheral compartment, these compartments being characterized by because they contain the same active ingredient. Each of these compartments has different and complementary diffusion kinetics.
- the invention also relates to a method of manufacturing this device and its application as a medicament.
- the present invention relates to transdermal devices preferably allowing transcutaneous administration of an active principle from at least one reservoir compartment and at least one matrix compartment, so as to combine the kinetics of skin diffusion and to reduce the latency time, in order to improve the performance and the safety of the administered product.
- a reservoir compartment is located in the center of the device, while a matrix compartment constitutes a peripheral zone around the central part. It can also be provided that the matrix compartment is located in the center and that the reservoir compartment constitutes a peripheral zone around the central part.
- the device according to the invention is particularly intended for active principles for which rapid action is sought with a possible relay in the form of an extension of the therapeutic effect. Rapid action is, for example, necessary in the case of local pain treatment, smoking cessation, hormone replacement therapy in humans.
- the transdermal devices are pharmaceutical forms which allow the percutaneous administration of certain active ingredients. It is recognized that this particular route of drug administration has advantages such as the avoidance of the first hepatic passage and a good tolerance of the patient to the treatment. Its faults are also known, and more particularly among them, it is necessary to cite the existence of a relatively long latency time. This parameter defines the time interval between the placement of the device on the skin and the first appearance of a measurable quantity of drug in the blood circulation, attesting to the passage of the latter. Overcoming this drawback amounts to administering a transdermal form at a regular rate, adapted to the pathology treated. Finally, this defect common to transdermal devices marketed to date, rules out any possibility of prescription as soon as immediate or rapid therapeutic relief is requested.
- This latency time depends on two factors, both the capacity of an active ingredient to be retained by the surface skin structures such as the stratum corneum, but also the technology chosen for the production of the device itself.
- transdermal devices a distinction is generally made between reservoir devices and matrix devices.
- the active ingredient is contained in a gel, most often hydroalcoholic, placed between a support film and a control membrane.
- a layer of material permeable to the active and adhesive ingredient - or intermediate permeation membrane - is present between the surface of the skin and the release control membrane. In other cases, this layer is located at the periphery.
- the active ingredient is contained in one or more matrix layers (usually based on self-adhesive polymers).
- matrix layers usually based on self-adhesive polymers.
- direct contact with the skin does not at least require the presence of an intermediate permeation membrane.
- the latency time will be low and generally little different from that observed with a topical form of hydroalcoholic gel type.
- matrix technology the latency time is generally longer, insofar as the active principle in dispersed or dissolved form in an adhesive polymer must first migrate through this adhesive medium before crossing the stratum corneum .
- the best example in the prior art relates to transdermal devices based on estradiol and more precisely the replacement of the original reservoir form by a matrix form.
- a first hormonal device was marketed (ESTRADERM®), in the form of a reservoir containing estradiol in the form of an alcoholic gel.
- a transparent protective membrane forms the reservoir itself, while on the side of the skin, this same reservoir is closed using a control membrane. The latter controls the release of the active ingredient and regulates the emptying of the reservoir.
- This unattractive device has proved to be relatively unstable, particularly during severe stress conditions, where, following losses of ethanol, modifications in the kinetic performance were later demonstrated.
- a second way consists in bringing together several transdermal devices each containing a single active principle.
- Such devices are for example described in WO 94/06383 or WO 90/06736; in this situation, it will be easier to control the quantity to be administered by adjusting the area concerned.
- the total surface is large and beyond 40 - 50 cm 2 , problems of adhesion or even skin tolerance are recognized.
- Other more minority descriptions such as WO 97/47305 or WO 96/19203 can be described as follows. In the first case, these are adjacent matrix devices preferably supported by the same support and protected by the same protector, but separated by a maximum distance of 10 mm.
- piroxicam indomethacin
- ibuprofen ketoprofen
- flurbiprofen flurbiprofen
- other local glucocorticoids piroxicam, indomethacin, ibuprofen, ketoprofen, flurbiprofen, and other local glucocorticoids
- anxiolytics and or antidepressants and more especially buspirone, fluoxetine, lorazepam; risperidone, selegiline;
- anti-nausea drugs such as chlorpromazine, promethazine, metoclopramide, domperidone;
- the subject of the present invention is a self-adhesive transdermal delivery device with double kinetics of an active principle comprising at least two adjacent compartments, in particular concentric, one being a reservoir type compartment and the other being a compartment. of matrix type, each of these compartments being designed to release the active principle according to release and diffusion characteristics specific to each compartment.
- the present invention relates to a device comprising a central compartment of reservoir type (2) surrounded by at least one central diffusion compartment of matrix type (6), and, according to a second variant to a device which comprises a central matrix type diffusion compartment (6a) surrounded by at least one reservoir type compartment (2a).
- the active principle is preferably an androgenic compound and even more preferably testosterone (17-hydroxandrost-4-ene-3-one).
- TRT hormone replacement therapy
- transdermal forms of testosterone marketed to date fulfills such an objective since it is either in the form of a reservoir patch (rapid release of the active principle), or in the form of a matrix patch with scrotal application (rapid release linked to the thin thickness of the skin of the scrotum).
- the present invention also relates to the use of the device according to the invention for the preparation of a medicament intended for a testosterone replacement therapy and in particular a daily, weekly or bi-weekly therapy for testosterone replacement, for the treatment of at least one pathology chosen from the group consisting of the treatment and / or prevention of hypogonadism, disorders of andropause, sexual impotence, disorders of fertility in humans, oligospermia , premature ejaculation.
- the transdermal device is such that the matrix type compartment comprises:
- the matrix type compartment essentially contains a self-adhesive matrix formed from at least one self-adhesive compound chosen from the group consisting of butylacrylate, ethylacrylate, butylmethacrylate 2-ethylhexylacrylate, isooctylacrylate, acrylic acid, methacrylic acid, vinyl acetate, hydroxyethylmethacn / lic acid, methylmethacrylate, methyl acrylate, EVA (ethylene-vinyl acetate), rubber derivatives, block copolymers SIS (styrene-isoprene-styrene), SBS (styrene-butadiene-styrene), SEBS (styrene-ethylene-butylene -styrene), in combination with sticky resins such as rosin resins, terpene resins, hydrogenated synthetic
- the matrix compartment includes a self-adhesive monolayer or multilayer matrix.
- a self-adhesive monolayer or multilayer matrix Preferably, it comprises: a) 40 to 80 parts by weight of acrylic copolymers, b) 5 to 20 parts by weight of a testosterone solvent chosen from
- - xanthan gums - cellulose derivatives such as, for example, sodium carboxymethylcellulose. d) 2 to 10 parts by weight of a testosterone hormone or one of its salts.
- peripheral compartment active adhesive matrix, called MAA in the remainder of the description
- MAA active adhesive matrix
- acrylic copolymer of low to medium molecular weight, with acid functionality characterized by the presence of acrylic acid among the monomers base giving it an acid number between 30 and 50; this copolymer having a vinyl acetate content of between 1 and 10% by weight relative to the total weight of basic monomers.
- This acrylic copolymer (for example DURO-TAK® 387-2052 or 87-2052 from the company NATIONAL STARCH & Chemical) is a “ready-to-use” self-crosslinked adhesive available in the form of an organic solution with a theoretical density close to 0.92 g / cm 3 and Brookfield viscosity (at 25 ° C, 12 rpm, mobile no.3) close to 2800 mPa.s.
- adjuvant polymers of the matrix which are suitable according to the invention, mention may be made of cellulose derivatives and more particularly sodium carboxymethylcellulose of molecular mass between 90,000 and 700,000 Da, derivatives of alkylcellulose type such as hydroxyethylcellulose or l hydroxypropylcellulose, high molecular weight polysaccharides and more particularly xanthan gums, and polymers of 1-vinyl-2-pyrrolidone type with a molecular mass of between 2,500 and 3,000,000 Da.
- polyvinylpyrrolidone the better solubility of which in alcoholic medium facilitates dispersion in an adhesive matrix as described in the present invention.
- the transdermal device according to the invention is such that the reservoir type compartment comprises: - an hydroalcoholic gel comprising the active principle and at least one thickening agent preferably of HPC type
- HPMC hydroxypropylmethylcellulose
- a membrane for controlling the release of the active principle a film for protecting the control membrane, and
- DEET N, N-diethyl-m- toluamide
- FIG. 5 represents a conventional embodiment of the transdermal device according to the invention, this figure is intended to be a non-limiting illustration of the invention.
- dimension 1 represents a support film
- dimension 2 represents a liquid active reservoir (RAL)
- dimension 3 represents a microporous membrane
- dimension 4 represents a protective film for the membrane
- dimension 5 represents an adhesive
- rating 6 represents an active adhesive matrix (MAA)
- symbol 7 represents a silicone protective film.
- FIG. 6 represents a second embodiment of the transdermal device according to the invention.
- the transdermal device is composed of a central compartment of matrix type surrounded by several rings of compartments of reservoir type and of alternating matrix type.
- the central compartment could, of course, be provided for the central compartment to be a reservoir type compartment surrounded by several rings of alternating matrix type and reservoir type compartments.
- FIG. 6 is a sectional view of a device which comprises • either alternating adjacent strips of reservoir type compartments and matrix type compartments, • or crowns of alternating reservoir type and matrix type compartments surrounding a central compartment of matrix type which has the shape of a disc.
- Dimension 1a represents a support film
- dimension 2a represents a liquid active reservoir (RAL)
- dimension 3a represents a microporous membrane
- dimension 4a represents a protective film for the membrane
- dimension 5a represents an adhesive
- the dimension 6a represents an active adhesive matrix (MAA)
- the symbol 7a represents a silicone protective film.
- the transdermal device is such that the reservoir type compartment comprises at least one material of hydrophilic type chosen from the group consisting of cellulose derivatives, natural gums, polyvinyl alcohols or of hydrophobic type chosen from group made up of elastomers thermoplastics, rubber derivatives, acrylic resins, block copolymers or combinations such as the combination of a polyacrylamide of an isoparaffin and a polyoxyethylene alcohol and is such that it is present in liquid, solid or semi form -solid
- the membrane for controlling the release of the active principle from the reservoir-type compartment comprises at least one compound chosen from the group consisting of butylacrylate, 2-ethylhexylacrylate, isooctylacrylate, acrylic acid, methacrylic acid, vinyl acetate, hydroxyethylmethacry acid that, methylmethacrylate, methyl acrylate, EVA, rubber derivatives, block copolymers SIS, SBS, SEBS, polyvinylidene fluoride fluoride fluoride
- this reservoir type device comprises a protective film for the membrane for controlling the release of the active principle coated with an anti-adhesive agent, said film being a material chosen from the group consisting of silicone papers, silicone polyesters or fluorinated polyesters
- the central compartment or active liquid reservoir will comprise a gelling agent of low molecular weight hydroxypropycellulose type (for example KLUCEL EF or HF® from the company AQUALON), the combination of a polyacrylamide, an isoparaffin containing 13 or 14 carbon atoms (C13-C14) and laureth 7 (for example SEPIGEL 305® from the company SEPPIC), an acrylic acid crosslinked via the presence of allyl sucrose and allyl pentaeryth ⁇ tol ethers (for example CARBOPOL 974P® from the company BF GOODRICH).
- a gelling agent of low molecular weight hydroxypropycellulose type for example KLUCEL EF or HF® from the company AQUALON
- the combination of a polyacrylamide, an isoparaffin containing 13 or 14 carbon atoms (C13-C14) and laureth 7 for example SEPIGEL 305® from the company SEPPIC
- Testosterone should preferably be used as a steroid component.
- the device according to the invention comprises an occlusive and inert support with a thickness of between 10 and 100 ⁇ m which protects the entire device according to the invention, it can be chosen from the films most often used in the formulation transdermal patches.
- the products generally used mention should be made of mono or multicomponent polyolefin compounds of the polyethylene, polypropylene, mono or bi-drawn type, of the polyester type compounds, the multilayer complexes consisting of the preceding materials associated for example with thin layers of aluminum, polyurethane thermoplastic elastomer complexes or combinations of vinyl acetate and ethylene (EVA) copolymers in the form of films or foam.
- EVA vinyl acetate and ethylene copolymers
- a multilayer film based on modified polyolefins and preferably based on ethylene-vinyl acetate copolymer (EVA) will be used.
- the protective film which protects the entire device but which must be removed at the time of installation will preferably be chosen from among the products having good cutting properties, inert with respect to the components of RAL and MAA, and whose anti-adhesion properties are more specifically adapted in order to allow the maintenance of contact between MAA and the protector, simultaneously with removal of this same protective film limited to the area of contact with the RAL.
- a polyester film with a thickness of between 50 and 100 microns will be used with a level of anti-adhesion of between 25 and 50 N / cm.
- the central part or liquid active reservoir comprises a membrane for controlling the release of the active principle, itself protected by a protective film.
- the characteristics of the latter are in fact specially studied in order to make this protective film to be secured to be removed at the time of application of the device. This phenomenon brings into play several forces:
- F1> F2 which indicates the need for the adhesive to remain on the support film when it is separated from the protective film
- F2 »F3 which indicates the presence of a rupture of this same adhesive with respect to the protective film of the RAL membrane, limited to the periphery of the latter.
- the absorption promoter present in one or other of the compartments, or even simultaneously in the RAL and the MAA it may be chosen from the components known to those skilled in the art making it possible to improve the criteria cumulative flows and quantities.
- a permeation agent chosen from the group consisting of alcohols, glycols, polyglycols, amides of the pyrrolidone type and derivatives, non-ionic surfactants of polysorbate type, alkyl ethers, poloxamers, saturated or unsaturated fatty acids will be used.
- fatty alcohols glycerides polyglycolyses alone or in mixture, glycols esters of propylene glycol or polyglycerol, fatty acid esters of the polyol type , alkylglyceryl ether, propylene glycol, glycerin, polyoxyethylene glyceryl, sorbitan, polyoxyethylene sorbitan, polyoxyethylene glycol, sugar esters, terpenic essential oils, diethyltoluamide, crotamiton, phospholipids, derivatives of lecithin, cetearyl isonononaonate, mannitan esters, xanthan gums and cellulose derivatives.
- the final device (RAL + MAA) will be packaged in a waterproof protection either of the sachet type or of the “film packaging” type (blister).
- the final device according to the invention has numerous advantages which can be explained as follows: - compared to the transdermal forms already on the market, the present invention makes it possible (in the case of a monotherapy based on testosterone) to reduce the time latency (characteristic element of reservoir technology) and ensuring regular skin passage thanks to good adhesion (characteristic element of matrix technology). - with regard to the compartment called MAA, the problems of solubility of testosterone in the adhesive have been resolved by the use of constituents more particularly capable of dissolving large amounts of active ingredient; it has proven very judicious to use the solvent power of organic compounds such as DEET.
- the present invention is characterized by the presence of a skin - patch interface largely saturated with active principle, responsible for the transcutaneous passage via a phenomenon of passive diffusion.
- active principle responsible for the transcutaneous passage via a phenomenon of passive diffusion.
- transdermal devices according to the invention are produced according to the techniques generally employed by those skilled in the art; these techniques are those of mixing, coating, drying, laminating, slitting and cutting.
- the present invention also relates to a method for preparing the self-adhesive transdermal device according to the present invention comprising the steps of: on the one hand,
- step 3 add to the premix obtained in step 3 at least one material of the acrylic copolymer type, capable of crosslinking to give a self-adhesive matrix,
- step 5 coat the mixture obtained in step 4 with a protective film for the membrane
- a method of manufacturing said transdermal device is also recommended according to the following steps: 1) prepare a premix of active principle in a solvent mixture (for example based on THF), 2) prepare a second premix based on adhesive, and polymers; (in the latter case, it is a question of ensuring the homogeneous dispersion of PVP, solid finely pulverized in a ready-to-use organic solution adhesive), 3) add to the premix 1 the theoretical amounts of ethanol and DEET then incorporate the whole into the above adhesive preparation,
- the product obtained in 5 constitutes an intermediate product; this is the active adhesive matrix (MAA),
- step 2 the production of a separate premix containing PVP and ethanol (step 2), - the removal of THF (step 1),
- step 5 the use of a short infrared type of drying mode (step 5).
- this gel it is preferable to allow this gel to "mature" for 10 to 12 hours before proceeding to the next step.
- ultrasound SONICS & Materials Ultrasonic Welder - power 64 %, pressure 1.5 to 2 bars.
- the assembly thus produced must generally undergo final cutting stages before packaging according to one or other of the possible systems, sachet or blister.
- the best mode of implementing the invention consists in using a transdermal device, the peripheral matrix compartment of which contains, for a total of 100 parts by weight (all of these elements are in no way limiting but are given at title of illustration): a) 63 to 73 parts by weight of an adhesive and self-crosslinking acrylic copolymer, in the form of a solution with approximately 47,5% w / v of copolymer 2-Ethylhexylacrylate, Butylacrylate, Acrylic Acid and , in as a crosslinking agent, of aluminum acetylacetonate, said “ready-to-use” adhesive copolymer having a glass transition temperature of the order of - 50 ° C; b) 5 to 25 parts by weight of soluble polyvinylpyrrolidone also called polyvidone, product obtained by polymerization of n-vinylpyrrolidone, with a density between 400 and 550 g / l and a molecular weight preferably between 44,000 and 54,000
- the best embodiment of the invention consists in using a transdermal device the central reservoir compartment of which contains, for a total of 100 parts by weight (all of these elements are in no way limiting but are given at title of illustration): e) 35 to 50 parts by weight of ethanol; f) 45 to 50 parts by weight of water; g) 0 to 20 parts by weight of N-N-diethyl-m-toluamide (DEET) or N, N-diethyl-3-methylbenzamide, as formulating agent, solvent for the active principle in the reservoir; h) 1 to 3 parts by weight of low molecular weight hydroxypropylcellulose; i) 1.5 to 5.75 parts by weight of testosterone in free form.
- DEET N-N-diethyl-m-toluamide
- i 1.5 to 5.75 parts by weight of testosterone in free form.
- This final mixture is transferred to the feed hopper of a coating head which makes it possible to deposit on a silicone polyester support an amount of the order of 120 ⁇ 10 g / m 2 . It is dried by applying a temperature gradient between 50 ° C and 100 ° C in order to evaporate the manufacturing solvents and allow the crosslinking of the acrylic adhesive. As a general rule, it is desirable to fully master this step, which greatly contributes to the quality of the finished product; according to said invention, this temperature gradient is associated with the possibility of varying the drying mode, preferably by first applying a mode known as "hot air with impact jet” then secondly a mode called “infrared short " . At the end of drying, the adhesive matrix, called Mat, in the dry state is laminated on a silicone transfer film.
- a mode known as "hot air with impact jet” then secondly a mode called “infrared short " .
- the silicone polyester film (of the PET SiV1 F 74H type) are cut in the form of discs with an area equal to the predetermined contact area of the central part of said device. These discs are deposited on the anvil of an ultrasonic welder in the case of a discontinuous manufacturing process.
- a nominal amount of the gel (intermediate product from step 2) is deposited in the center of the polyethylene film.
- This deposit of the order of a gram is carried out using a precision filling metering device.
- the protective film (of the DBLF 2050 type) is laminated, the bonding of which can possibly be improved via a chemical or physical pretreatment.
- An intermediate assembly is obtained by the application of ultrasound under conditions suitable for guaranteeing the tightness of the reservoir, the Res reservoir is thus obtained.
- a fifth step it involves laminating the reservoir obtained previously to the intermediate product from the first manufacturing step and then performing the final cutting of the device according to the invention.
- Example 2 The procedure is analogous to Example 1, replacing the acrylic copolymer DURO-TAK 387-2052 by a self-crosslinking acrylic copolymer, in the form of a solution at about 28% w / v of Butyl acrylate, of 2-Ethylhexylacrylate , Acrylic Acid, 2-hydroxyethylacrylate, methylmethacrylate and, as crosslinking agent, aluminum acetylacetonate and t-amylperoxypivolate, said "ready-to-use" adhesive copolymer having a transition temperature glassy at -26 ° C and being marketed by the company NATIONAL STARCH & Chemical under the name DURO-TAK 87-2074®.
- Example 2 The procedure is analogous to Example 1, reducing the amount of the solvent for the active principle, ie an amount of N-N-diethyl-m-toluamide in the mixture before coating, of the order of 6%.
- Example 2 The procedure is analogous to Example 1, replacing the polyvinylpyrrolidone with another polymeric agent, preferably sodium carboxymethylcellulose, sold under the name of CARMELLOSE® sodium by the company AQUALON.
- another polymeric agent preferably sodium carboxymethylcellulose, sold under the name of CARMELLOSE® sodium by the company AQUALON.
- Example 6 The procedure is analogous to Example 1, replacing the polyvinylpyrrolidone with another polymeric agent, preferably a xanthan gum, sold under the name of KELTROL CR® by the company KELCO.
- Example 6 The procedure is analogous to Example 1, replacing the polyvinylpyrrolidone with another polymeric agent, preferably a xanthan gum, sold under the name of KELTROL CR® by the company KELCO.
- Example 2 The procedure is analogous to Example 1, replacing the acrylic copolymer DURO-TAK 387-2052 with a non-self-crosslinking acrylic copolymer, in the form of a solution at about 28% w / v of Butylacrylate, of 2-Ethylhexylacrylate , acrylic acid, 2-hydroxyethylacrylate, methylmethacrylate, said “ready-to-use” adhesive copolymer having a glass transition temperature of - 26 ° C. and being marketed by the company NATIONAL STARCH & Chemical under the name DURO-TAK 87-2051®.
- Example 2 The procedure is analogous to Example 1, replacing the DURO-TAK acrylic copolymer of organic solution type with an acrylic copolymer in aqueous emulsion based on ethylacrylate, butylacrylate and butylmethacrylate monomers, of viscosity between 50 and 250 mPas and at solid content between 54.0 and 58.0% Comparative example C1
- This reservoir device is constituted by an alcoholic testosterone gel based on hydroxypropylcellulose, containing absorption promoting agents such as methyllaurate and glycerolmonooleate.
- the diffusing surface consisting of a control membrane is centered around a non-active adhesive peripheral part which allows the patch to be held on an area of non-scrotal application.
- This large surface reservoir device (60 cm 2 ) consists of a hydroalcoholic testosterone gel based on hydroxypropylcellulose devoid of absorption promoting agents.
- the diffusing surface consisting of a control membrane is centered around a non-active adhesive peripheral part which allows the patch to be held on an area of non-scrotal application.
- Tables 1a and 1b respectively represent the quantities of testosterone released: ex vivo permeation on animal skin either in cumulative quantities ( ⁇ g / cm 2 - fig. 1a), or in flow ( ⁇ g / cm 2 / h - fig. 1b ) in function of time (hours), in the case of non-associated transdermal devices, ie either of the matrix type or of the reservoir type.
- a Mat type matrix was used and to represent the reservoir type device, a Res type gel was used.
- the curves connecting diamonds ( ⁇ ) correspond to the results obtained with the Mat matrix and the curves connecting squares (B) correspond to the results obtained with the device Res. Tests 2a and 2b
- Tables 2a and 2b respectively represent the quantities released: the permeation of testosterone ex vivo on animal skin either in cumulative quantities ( ⁇ g / cm 2 - fig. 2a), or in flow ( ⁇ g / cm 2 / h - fig. 2b) as a function of time (h), in the case of transdermal devices of the reservoir type, respectively as Comparator either C1 or C2.
- the curves connecting diamonds (*) correspond to the results obtained with the comparative device C1 (Androderm) and the curves connecting the squares (B) correspond to the results obtained with the comparative device C2 (Testoderm).
- Tests 3a and 3b To carry out tests 3a and 3b, a Mat type matrix and a Res type reservoir were used. The results of these tests are presented in the table below. The quantities of testosterone released: the ex-vivo permeation on animal skin in cumulative quantity ( ⁇ g / cm 2 ) as a function of time (in hours) is presented.
- Tables 3a and 3b respectively represent the quantities released of testosterone ex vivo on animal skin in cumulative quantities ( ⁇ g / cm 2 ), either after 2 hours (Table 3a), or after 24 hours (Table 3b) in the case of a double compartment transdermal device according to the invention.
- Figure 3a corresponds to the cumulative quantities at 2 hours and Figure 3b corresponds to the cumulative quantities at 24 hours.
- the following table represents the quantities of testosterone released: ex vivo permeation on animal skin in flow ( ⁇ unit / h).
- FIG. 4 represents the quantities released of testosterone ex vivo on animal skins in flow ( ⁇ g / cm 2 / h), in the case of a double compartment transdermal device according to the invention.
- the curve connecting diamonds ( ⁇ ) corresponds to the results obtained with the matrix 30
- the curve connecting the squares (B) corresponds to the results obtained with the reservoir 10
- the curve connecting triangles (A) corresponds to the results obtained with the association matrix 30 + reservoir 10
- the curve connecting the crosses (x) corresponds to the results obtained with the reservoir 5
- the curve connecting the crosses crossed vertically (*) corresponds to the results obtained with the association matrix 30 + reservoir 5
- the curve connecting the points (•) corresponds to the results obtained with the reservoir 15
- the curve connecting vertical lines (I) corresponds to the results obtained with the association matrix 30 + reservoir 15.
- transdermal device according to the invention makes it possible both to reduce the latency time and to ensure regular skin passage.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9915071A FR2801507B1 (fr) | 1999-11-30 | 1999-11-30 | Dispositif transdermique auto-adhesif comprenant un reservoir et une matrice contenant le meme principe actif, son procede de preparation et ses utilisations |
FR9915071 | 1999-11-30 | ||
PCT/FR2000/003344 WO2001039754A1 (fr) | 1999-11-30 | 2000-11-30 | Dispositif transdermique comprenant un reservoir et une matrice contenant le meme principe actif |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1233764A1 true EP1233764A1 (fr) | 2002-08-28 |
Family
ID=9552714
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00985366A Withdrawn EP1233764A1 (fr) | 1999-11-30 | 2000-11-30 | Dispositif transdermique comprenant un reservoir et une matrice contenant le meme principe actif |
Country Status (7)
Country | Link |
---|---|
US (1) | US20030082227A1 (fr) |
EP (1) | EP1233764A1 (fr) |
JP (1) | JP2003515555A (fr) |
AU (1) | AU2180801A (fr) |
CA (1) | CA2392402A1 (fr) |
FR (1) | FR2801507B1 (fr) |
WO (1) | WO2001039754A1 (fr) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10137405A1 (de) * | 2001-07-31 | 2003-02-20 | Beiersdorf Ag | Verfahren zur kontinuierlichen Herstellung und Beschichtung von Selbstklebemassen auf Basis von SBC mit mindestens einem pharmazeutischen Wirkstoff |
MY139721A (en) * | 2002-04-19 | 2009-10-30 | Cpex Pharmaceuticals Inc | Pharmaceutical composition |
AR033748A1 (es) | 2002-05-15 | 2004-01-07 | Thalas Group Inc | Un dispositivo para la administracion transdermica de sustancias farmacologicamente activas que comprende dos capas adhesivas superpuestas y un procedimiento para prepararlo |
WO2004098472A1 (fr) * | 2002-08-30 | 2004-11-18 | Watson Pharmaceuticals, Inc. | Systemes et techniques d'administration transdermique |
US20040259852A1 (en) | 2003-06-18 | 2004-12-23 | White Hillary D. | Trandsdermal compositions and methods for treatment of fibromyalgia and chronic fatigue syndrome |
US8883769B2 (en) | 2003-06-18 | 2014-11-11 | White Mountain Pharma, Inc. | Methods for the treatment of fibromyalgia and chronic fatigue syndrome |
US20050036953A1 (en) * | 2003-08-13 | 2005-02-17 | Moshe Arkin | Topical compositions of ammonium lactate |
US20050037040A1 (en) * | 2003-08-13 | 2005-02-17 | Moshe Arkin | Topical compositions of urea and ammonium lactate |
US20050042182A1 (en) * | 2003-08-13 | 2005-02-24 | Moshe Arkin | Topical compositions of urea |
US20050025833A1 (en) * | 2003-07-16 | 2005-02-03 | Chaim Aschkenasy | Pharmaceutical composition and method for transdermal drug delivery |
US20050020552A1 (en) * | 2003-07-16 | 2005-01-27 | Chaim Aschkenasy | Pharmaceutical composition and method for transdermal drug delivery |
US20050042268A1 (en) * | 2003-07-16 | 2005-02-24 | Chaim Aschkenasy | Pharmaceutical composition and method for transdermal drug delivery |
US20060127463A1 (en) * | 2004-12-15 | 2006-06-15 | Nugara Peter N | Composite structure including a low vinyl acetate layer |
DE102004062614B4 (de) * | 2004-12-24 | 2011-12-29 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System mit aktivierbarer Übersättigung und kontrollierter Permeationförderung sowie Verfahren zu dessen Herstellung |
MX2011003510A (es) | 2008-10-02 | 2011-06-17 | Mylan Inc | Metodo para fabricar un laminado adhesivo de multiples capas. |
US9642862B2 (en) | 2010-11-18 | 2017-05-09 | White Mountain Pharma, Inc. | Methods for treating chronic or unresolvable pain and/or increasing the pain threshold in a subject and pharmaceutical compositions for use therein |
EP2968652B1 (fr) | 2013-03-13 | 2020-07-22 | Avery Dennison Corporation | Amélioration de propriétés adhésives |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5788983A (en) * | 1989-04-03 | 1998-08-04 | Rutgers, The State University Of New Jersey | Transdermal controlled delivery of pharmaceuticals at variable dosage rates and processes |
US5152997A (en) * | 1990-12-11 | 1992-10-06 | Theratech, Inc. | Method and device for transdermally administering testosterone across nonscrotal skin at therapeutically effective levels |
DE19844079A1 (de) * | 1998-05-22 | 1999-11-25 | Novosis Pharma Ag | Biphasische Transdermalsysteme |
-
1999
- 1999-11-30 FR FR9915071A patent/FR2801507B1/fr not_active Expired - Fee Related
-
2000
- 2000-11-30 CA CA002392402A patent/CA2392402A1/fr not_active Abandoned
- 2000-11-30 EP EP00985366A patent/EP1233764A1/fr not_active Withdrawn
- 2000-11-30 WO PCT/FR2000/003344 patent/WO2001039754A1/fr not_active Application Discontinuation
- 2000-11-30 US US10/148,256 patent/US20030082227A1/en not_active Abandoned
- 2000-11-30 AU AU21808/01A patent/AU2180801A/en not_active Abandoned
- 2000-11-30 JP JP2001541487A patent/JP2003515555A/ja active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO0139754A1 * |
Also Published As
Publication number | Publication date |
---|---|
FR2801507B1 (fr) | 2003-06-27 |
WO2001039754A1 (fr) | 2001-06-07 |
FR2801507A1 (fr) | 2001-06-01 |
CA2392402A1 (fr) | 2001-06-07 |
JP2003515555A (ja) | 2003-05-07 |
AU2180801A (en) | 2001-06-12 |
US20030082227A1 (en) | 2003-05-01 |
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