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
  • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer

Definitions

• the present invention relates to transdermal therapeutic system
• Drugs are normally administered and / or delivered in the body of patient by injections, tablets and syrups and like manner. Specific problems arise in the pharmaceutical industry for delivery of drugs in the body (which may be human or animal) by above forms of delivery. In view of above, various attempts have been made to deliver the drugs, medicinal and pharmaceutical ingredients in the body by other forms such as transdermally through the skin for which purpose various devices and / or methods have been devised.
• transdermal therapeutic system for the delivery various drugs, medicines, pharmaceutical ingredients transdermally through the skin was an important field of drug delivery for the pharmaceutical industry, due to specific problems that arise with other forms of drug delivery like injections, tablets and syrups.
• Transdermal patches designed as matrix type, reservoir type, drug-inadhesive type, monolithic type, multi-layer type are available all over the world for various drugs and pharmaceutical ingredients and medicines, but they are not found economical, easy to manufacture , handle the same and are not eco- friendly.
• transdermal patches are formulated from various adhesives like silicon, acrylic, rubber etc with various polymers and co-polymers, along with excipients, stabilizers, plasticizers, catalysts, anti-microbials and other substances like enhancers, co-enhancers, cross-linkers etc.
• Patent EP0561983 describes a transdermal patch for nitroglycerin with acrylic adhesive and sorbitan monooleate, propylene glycol as excipients along with others.
• transdermal patches generally have some of the following physical entities: release liner, rate control membrane, reservoir layers, adhesive layers, backing layer.
• release liner As an example, .Chandrasekaran et al., U.S. Pat. No. 4,201,211, describes a five layer transdermal system.
• transdermal patches are sealed in various size pouches that incorporate characteristics to suit various requirements to keep the transdermal patch away from atmospheric gases and dust as well as from moisture and provide necessary stability to the ingredients.
• the pouches or packages of the transdermal patches are generally made up of paper, metallic foils, polymer films or a combination thereof with incorporating various heat sealable components or pressure sealable components.
• Skin is generally covered with dust and dead cells that may act as additional barriers to drug transfer thus resulting in decrease in adhesion of the patch on the skin.
• adherence of a transdermal patch over skin causes occlusion: trapping of moisture between the patch and the skin.
• Managing the degree of occlusion is an important aspect of designing a transdermal system. It effects the flux of drug across the skin significantly high degree of occlusion can decrease the adhesion of the patch, thus the patch can dislodge from the skin.
• little or in-significant occlusion can make the patch adhere aggressively with the skin and can result in skin irritation and as well as skin injury when the patch is removed. Occlusion by and large depends on the moisture vapor transfer rate (MVTR) characteristic of the backing layer.
• MVTR moisture vapor transfer rate
• Occlusion has bearing on the cold flow property of the adhesive component of the patch. As the occlusion decreases, the adherability of the adhesive over the skin increases and thus increasing the possibility of cold flow thus leaving adhesive deposits over the skin once the patch is removed after its use.
• Transdermal patches are worn for extended time periods depending on the drug as well as its usage and generally span from one day to seven days. Once the time period is elapsed the patch needs to be removed and a new patch is to be worn. Compliance for this application procedure depends on the patient's recall of the time when he or she worn the patch. This results in significant patient compliance issues.
• the drug ingredient has to diffuse though the skin barrier to be available to the body.
• the transfer of drug through the skin generally modeled along the Fick's laws of diffusion.
• the concentration of drug at the site of application profoundly effects the flux of drug across the skin barrier.
• a high concentration of drug at the application site results in an increase of flux of drug through the skin into the body.
• One option to achieve a high concentration is to supersaturate the adhesive with drug.
• Another option was to create high concentrated deposits of drug formulation at various parts of the patch.
• transdermal system patch made according to teachings of the present invention which not only overcomes above disadvantages but also is easier to manufacture and use economical and patient friendly and does not create major cosmetic problems.
• a major aspect of the present embodiment is to provide a design for a increasing the drug concentration at the vicinity of the skin by incorporation of a drug formulation mesh or a net in close contact with the skin with an adhesive layer above it.
• An aspect of the present invention is to provide a inclusive common physical layer that performs as a release liner as well as one side of the pouch that carries the transdermal patch.
• Another aspect of the present embodiment is to provide for a in-built skin scraper or a cleaner as a part of the transdermal system that assists in removal of dust, debris, dead cells etc invariably present on the application site over the skin thus assisting in better adherability and improved drug transfer flux characteristics.
• Yet another aspect of the present invention is to provide for a physical system that can control the degree of occlusion selectively over the area of the patch.
• Another aspect of the present invention is to provide a unique design for application of large surface patches to various sites on the body.
• a further aspect of the invention is to provide for a physical shaping of the transdermal patch for it to stay in place on the skin thorough out the time period of its intended use.
• One important aspect of the present invention is to provide for a in-built color coded indicative system that can visually cue the patient for the removal of the patch and to put on a new one in needed.
• transdermal therapeutic system comprising of pouch(l) made of metallic foil, polymeric film, paper, laminates of these or a combination thereof which is sealed over the ages thermally, ultrasonically by application of pressure, gluing or a combination thereof, scraper layer (2) made of polymeric or metallic or non metallic powder or particles coated thereon , backing layer (3)which is provided on the top of the pouch, adhesive embedded with a drug mesh or net (4) at the bottom which is in contact with the pouch.
• Said adhesive layer and drug mesh/ net combination is in close contact with the skin(5).
• Said drug mesh is made of supersaturated drug in the form of solution powder, gel, particles on in a combination thereof, embedded, loaded, sprayed on to a various polymer fibers, strands such as polyethylene, polyester, polyurethane foam, polypropylene, PTFE, PBT, fabrics, non-woven, laminates and a combination thereof.
• Permeation enhancers are included in the mesh as and when desired.
• Final laminate is made with drug mesh, adhesive and backing layer.
• bands are used to keep the transdermal patch in place.
• Said bands which may be extended are two or more in number and are attached to the side of transdermal patch which is made of metal foils, polymer films, woven fabrics, non-woven fabrics, laminates or a combination thereof.
• Fine coat of bio-compatible adhesive is applied to the arms on the inner side which touch the skin.
• Color coding cue is applied to transdermal patch which assists in improved compliances of the patient to remove the patch after desired time DETAILED DESCRIPTION OF THE INVENTION
• Fig.l shows an embodiment of the present invention comprising of pouch, scraper layer, backing layer, adhesive embedded with a drug mesh or net at the bottom.
• Fig.2A shows another embodiment of the present invention comprising of the backing layer incorporated with micro perforations or pin holes spanning various areas.
• Fig.2B shows further embodiment of the present invention comprising of the backing layer incorporated with micro perforations or pin holes spanning various areas.
• Fig.2C shows an embodiment of the present invention comprising of the backing layer incorporated with micro perforations or pin holes spanning various areas.
• Fig.3 shows the view of backing layer, adhesive and drug mesh laminate applied at a site on the skin.
• Fig.4 shows a schematic of the present invention comprising of physical entity shaping of transdermal patch.
• Fig.5 shows an embodiment of the present invention with color coded cue developed over a defined time period.
• Fig.6 shows yet another schematic of the present invention comprising of an alternative physical entity shaping of transdermal patch.
• the pouch that carries the transdermal patch till the time of use is generally made of metallic foil, polymeric film, paper, laminates of these or a combination thereof. It is sealed over the edges thermally, ultrasonically, by application of pressure, gluing ( or a combination thereof. A four side seal is preferred for the present embodiment.
• the scraper layer is made up of polymeric or metallic or non-metallic powder or particles that are coated preferably by a spray on to inner side of the upper layer of the pouch.
• the powder or particles can also be embedded into the pouch layer itself while it is manufactured from metallic foil, polymeric film, paper, laminates of these or a combination thereof.
• the particles preferably be coated or embedded firmly on the pouch layer so that they would not the dislodged while being used during the application.
• the top side portion of the pouch that has the scraper made underneath is used to rub over the skin to remove any dust, debris or dead cells from over the site of application. Removal of this debris generally results in improved adhesion as well as better permeation of the drug moiety across the skin barrier.
• the lower side of the pouch has the transdermal patch with backing layer on the top and the adhesive and the drug mesh/net at the bottom in contact with the pouch. (Fig.l)
• the patch now can easily be removed from the lower side of the pouch by peeling of the un-eclipsed portion of pouch that is available beside the patch.
• This aspect of the present embodiment assists in quick removal of patch from the pouch and its subsequent application on the skin and additionally cuts down the amount of materials needed to manufacture the patch by removing the requirement of a release liner for the patch.
• the backing layer is made up of polymer film, paper, woven fabric, non-woven fabric, laminates of these or a combination thereof.
• MVTR moisture vapor transfer rate
• various combinations of polymers and co-polymers ranging from polyethylene, polyester, polyurethane foam, polypropylene, PTFE, PBT, laminates and combination thereof are used.
• the present embodiment provides for an design element for precise control of occlusion.
• Fig. 2 illustrates the use of micro perforations, micro pin holes in various arrangements (A, B & C) on the backing layer.
• arrangement A consists of perforation all over the backing layer. This embodiment provides almost zero occlusion aspect on to the transdermal patch which may result in aggressive holding of patch over the skin.
• arrangement B shows perforations made along the perimeter of the backing layer. This arrangement provides for less occlusion but good adhesion along the edges of the patch while still providing for good amount of occlusion in the middle that helps the penetration of certain type of drug moieties across the skin.
• arrangement C shows perforations made around the center of the patch. This arrangement provides for less occlusion in the center but more at the edges of the patch. The patch in this design has less chance to develop cold flow as the occlusion is more at the edges of the patch.
• the present embodiment provides for a adhesive layer and drug mesh/net combination in close contact with the skin as illustrated in Fig.3.
• the adhesive layer is made of silicon, rubber, acrylic type of adhesives or a combination thereof. If desired the drug moiety can be dissolved into the adhesive to make a drug-in-adhesive formulation. Alternatively, a choice of permeation enhancers, stabilizers, catalysts, excipients or a combination thereof can be included in the adhesive Jayer as desired. As illustrated in Fig.3, the drug mesh is sandwiched between the adhesive layer and skin. This arrangement provides for a very close contact of the drug moiety with the skin. Since the drug concentration is very high (supersaturated) in the drug mesh, according to the diffusion model, an increase in flux of drug moiety across the skin is seen.
• the drug mesh is made up of supersaturated drug in the form of solution, powder, gel, particles on in a combination thereof, embedded, loaded, sprayed on to various polymer fibers, strands like polyethylene, polyester, polyurethane foam, polypropylene, PTFE, PBT, fabrics, non-woven, laminates and a combination thereof.
• a choice of permeation enhancers, stabilizers, catalysts, excipients or a combination thereof can be included in the mesh as desired.
• the final laminate is made with' drug mesh, adhesive and backing layer.
• the sandwiched drug mesh is kept in close contact with the skin, without dislodging, thus assisting the drug to penetrate the skin in increasing amounts.
• transdermal patch needs to stay in place on the skin for extended periods of time, formulations, tend to increase the adhesive strength thus increasing the chances of cold flow as well as skin irritation and inflammation.
• Fig.4 illustrates a physical entity shaping with the use of bands to keep the transdermal patch in place without the increase of adhesive strength of the adhesive.
• the two extended bands attach to the side of the transdermal patch and are made of metal foils, polymer films, woven fabrics, non-woven fabrics, laminates or a combination thereof.
• a fine coat of bio-compatible adhesive is applied to these arms on the inner sides that touch the skin.
• Transdermal patches are applied preferably to the arms.
• the extended bands wrap around the arm or the leg or a thigh and overlap on each other' at the other end.
• the patch is adhered to the site of application stays put without dislodging due to the extra strength that is provided by the bands.
• An alternative is to use two lines of fine mesh or a net, preferably transparent for cosmetic reasons.
• Time based color coding cue (Fig.5) is an important aspect of the present invention.
• the development of a colored entity over the transdermal patch assists in improved compliance of the patient to remove the patch after the desired time period and put another one.
• the time period can range from twelve hours to more than seven days in some instances, compliance is assured with this aspect of the present invention.
• the color coding cue is bought in by the exposure of the transdermal patch to the atmosphere as it is removed from the protective pouch and applied on the skin.
• Constant and extended exposure of the color coding formulation to gases, carbon dioxide, nitrogen, moisture, preferably oxygen or a combination thereof is used to bring about the chemical, physical changes that appear as color development at the desired time period over the backing layer as illustrated in Fig.5.
• Designing various formulations brings about color change at and about the desired time period that can span from twelve hours to more than seven days.
• a color coding cue in the shape of a circle in the center of the transdermal patch on the backing layer is illustrated in Fig.5.
• any abstract shape or shapes desired can be incorporated.
• words of required text can be printed using the color code formulation over the backing layer that appear and give instructions to the patient at the desired time period.
• Drug moieties differ widely in molecular size, chemical structure etc thus effecting the permeation of the drugs through the skin.
• Another important aspect is the therapeutic levels that are needed for a drug in the body to perform its functions.
• the transdermal patch is shaped as a single band that is wrapped " around the site of application preferably around the arm or a leg or a thigh.
• the length of the patch is enough to go around the arm or the leg and to overlap the one end on the other.
• the main aspect of the embodiment is the thinness of the patch thus providing better adherence and occlusion properties.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Dermatology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Preparation (AREA)
• Media Introduction/Drainage Providing Device (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

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• 2009
  • 2009-11-20 RU RU2012119297/15A patent/RU2012119297A/ru not_active Application Discontinuation
  • 2009-11-20 EP EP09850203A patent/EP2485719A4/de not_active Withdrawn
  • 2009-11-20 WO PCT/IN2009/000675 patent/WO2011042913A1/en active Application Filing
  • 2009-11-20 AU AU2009353789A patent/AU2009353789A1/en not_active Abandoned

Patent Citations (2)

Non-Patent Citations (1)

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