+

WO2008128280A1 - Procédé et système pour l'administration transdermique d'un agent actif volatil - Google Patents

Procédé et système pour l'administration transdermique d'un agent actif volatil Download PDF

Info

Publication number
WO2008128280A1
WO2008128280A1 PCT/AU2008/000537 AU2008000537W WO2008128280A1 WO 2008128280 A1 WO2008128280 A1 WO 2008128280A1 AU 2008000537 W AU2008000537 W AU 2008000537W WO 2008128280 A1 WO2008128280 A1 WO 2008128280A1
Authority
WO
WIPO (PCT)
Prior art keywords
spray
volatile
nicotine
skin
active
Prior art date
Application number
PCT/AU2008/000537
Other languages
English (en)
Inventor
Adam Watkinson
Barrie Charles Finnin
Nina Frances Wilkins
Original Assignee
Acrux Dds Pty Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Acrux Dds Pty Ltd filed Critical Acrux Dds Pty Ltd
Publication of WO2008128280A1 publication Critical patent/WO2008128280A1/fr

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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse

Definitions

  • This invention relates generally to a system and method for treating conditions responsive to volatile active agents.
  • the invention relates to transdermal administration of nicotine to effect smoking cessation and transdermal administration of selegiline for treatment or prophylaxis of Parkinson's disease and related disorders.
  • U.S. Patent No. 4,868,218 describes the transdermal application of selegiline in the treatment of depression. Nicotine and nitroglycerine are drugs, normally liquid at or about room temperatures, for which there is considerable art on transdermal use.
  • Nicotine is a principal component of tobacco, and the most pharmacologically active. It is physically addictive, making it extremely difficult for a smoker to quit. Smoking a cigarette delivers nicotine vapors to the lungs, where nicotine is rapidly absorbed through the arteries and delivered to the brain. Nicotine interacts with nicotinic cholinergic receptors in the brain to induce the release of neurotransmitters and produce an immediate reward-the "rush" that smokers experience-that is associated with a rapid rise in blood level. [0004] Most reported rapid on-set systems, such as those described above, use drugs having the salt form of the drug which is less volatile and has a much higher boiling point than the free-base form of the drug.
  • Transdermal drug delivery systems use the free-base form of the drug, all suffer from the loss of the drug during manufacture of the transdermal system. This loss is due to the volatile nature of the drug during the drying stage in the production of cast systems.
  • European patent application 593,807 describes a transdermal system that attempts to solve the problem of liquid drug loss. However, this transdermal system requires the use of multilayers of polymeric adhesive which contributes toward increased cost and complexity.
  • Another related problem with liquid, low molecular weight drugs is the plasticizing effect that the drug has on the polymer matrix in the transdermal drug delivery system.
  • the low molecular weight base form of the drug has an excessive plasticizing effect on the polymer, resulting in a composition that is "leggy or gummy.” This renders the composition unsuitable for adhesion to the epidermis.
  • PCT Pub. No. WO 96/40085 describes transdermal matrix patches for administering drugs such as selegiline, nitroglycerin and nicotine that are liquid at normal room temperature.
  • the publication suggests making a monolithic matrix of the drug in an adhesive by mixing one or more polymeric adhesives, preferably polyacrylate and polysiloxane, and the drug in a volatile solvent, casting the mixture, and evaporating the solvent.
  • volatile solvents isopropanol, ethanol, xylene, toluene, hexane, cyclohexane, heptane, ethyl acetate and butyl acetate.
  • Nicotine delivery via inhalation offers the benefit of addressing the psychological component of cigarette smoking in addition to the physiological dependence on nicotine. Nicotine inhalation systems release nicotine as a vapor (see U.S. Pat. Nos. 5,167,242; 5,400,808; 5,501 ,236; 4,800,903; 4,284,089; 4,917,120; 4,793,366), aerosol (see U.S. Pat. Nos. 5,894,841 ;
  • US Patent 6299900 describes a non-occlusive transdermal composition which contains an active which may be selected from a wide range of options, a penetration enhancer which is preferably a sunscreen ester and volatile solvent.
  • an active which may be selected from a wide range of options
  • a penetration enhancer which is preferably a sunscreen ester and volatile solvent.
  • the invention provides a method of transdermal administration of a volatile active agent, preferably selected from Nicotine and Selegiline, comprising applying a solution containing the volatile active dissolved in a volatile solvent in a concentration in the range of from 0.5 to 25% by weight to an area of skin without occlusion of the applied solution.
  • a volatile active agent preferably selected from Nicotine and Selegiline
  • the solution is applied by means of a spray, however the invention may equally work where the solution is applied as an aerosol, a roll-on or by any other spreading device.
  • the spray is typically allowed to dry without occlusion such as with a patch plaster or other applied physical barrier.
  • the invention provides a system for non-occlusive transdermal delivery of a volatile active, preferably selected from Nicotine and Selegiline, to an area of skin comprising a container; within the container a solution containing the volatile active dissolved in a volatile solvent in a concentration in the range of from 0.5 to 25% by weight; an applicator nozzle for delivering a spray of the solution onto the skin; and preferably a nozzle housing about the nozzle (and optionally also housing the container); and preferably a spacer extending from the housing for placement against the skin to stabilize the nozzle in spaced relationship to the area of skin.
  • a volatile active preferably selected from Nicotine and Selegiline
  • a volatile solvent preferably selected from ethanol, isopropanol and mixtures thereof
  • the metered dose contains in the range of from 0.9 to 22.5 mg of nicotine and wherein the spray is preferably allowed to dry without occlusion such as with a patch plaster or other applied physical barrier.
  • a metered dose spray of a composition comprising in the range of from 0.5 to 10% (preferably from 3 to 10% and most preferably from 4 to 8%) by weight of selegiline in a volatile solvent (preferably selected from ethanol, isopropanol and mixtures thereof) wherein the metered dose contains in the range of from 0.45 to 20 mg of Selegiline, preferably from 2.7 to 9 mg and most preferably from 3.6 to 7.2 mg selegiline.
  • a volatile active and particularly nicotine or selegiline
  • a volatile solvent particularly ethanol, isopropanol or a mixture thereof
  • manufacture of a medicament composition for treatment of a disease preferably selected from smoking addiction and Parkinson's disease
  • a unit dose spray comprising from 0.45 to 22.5 mg to an area of skin of the subject
  • the composition comprises the volatile active dissolved in a volatile solvent in a concentration in the range of from 5 to 25% by weight of the composition.
  • skin is used to refer to the organ of the integumentary system made up of multiple layers of epithelial tissues that guard underlying muscles and organs.
  • skin as used herein does not include mucous membranes (or mucosae).
  • mucous membranes refers to the linings of mostly endodermal origin, covered in epithelium, and are involved in absorption and secretion.
  • mucous membrane refers generally to any of the mucous membranes in the body such as the oral cavity and respiratory system. Thus, buccal, sub lingual, gingival, palatal, throat and lung absorption are not the included in the reference to transdermal administration.
  • non-occlusive is used herein in its broadest sense to refer to not trapping or closing the skin to the atmosphere by means of a patch device, fixed reservoir, application chamber, tape, bandage, sticking plaster, or the like which remains on the skin at the site of application for a prolonged length of time.
  • stratum corneum is used herein in its broadest sense to refer to the outer layer of the skin, which is comprised of (approximately 15) layers of terminally differentiated keratinocytes made primarily of the proteinaceous material keratin arranged in a ' brick and mortar ' fashion with the mortar being comprised of a lipid matrix made primarily from cholesterol, ceramides and long chain fatty acids.
  • the stratum corneum creates the rate- limiting barrier for diffusion of the active agent across the skin.
  • propellant is used to refer to materials which are aerosol spray propellants and generally have a boiling point lower than room temperature. Propellants are not considered as part of the volatile solvent in compositions of the invention and amounts based on the weight of the spray composition do not include propellants or materials which have a boiling point below 25 0 C.
  • volatile active agent refers to pharmaceutically active agents that are liquid at or below the skin temperature of 32 Q C, and suffer from significant loss due to evaporation during product manufacture and from the dosage form during storage or product use.
  • the active agents used in the method and system of the invention are volatile low molecular weight drugs of less than 500 Daltons, which are generally liquid at skin temperature (32 Q C) in the free base form. Nicotine and selegiline are preferred examples of such active agents and nicotine is the most preferred active agent.
  • the composition of the invention contains a solution of the active agent in a volatile solvent.
  • the active agent is present in an amount of from 0.5 to 25% by weight of the composition.
  • the composition may comprise nicotine in an amount from 5 to 25% by weight and preferably from 10 to 20% by weight and most preferably from 12 to 18% by weight of the composition.
  • the active agent is selegiline
  • the composition may comprise selegiline in an amount from 0.5 to 10% by weight and preferably from 3 to 10% by weight and most preferably from 4 to 8% by weight of the composition.
  • the present invention eliminates the key detrimental issues associated with patch and gel/cream-based technologies.
  • the main generic issue is localised irritation or inflammation.
  • the key issues are accurate dosage and "messiness".
  • the system of the present invention is fast drying, quickly absorbed, non-irritating to the skin, invisible after application and will not fall off during use.
  • this composition and dosage form is particularly useful since the manufacturing process provides significant advantages when using volatile active agents.
  • this particular composition requires no heating during manufacture, and thus will not suffer from the loss of volatile active agent, resulting in reduced manufacturing site contamination, a more stable composition and ultimately cost savings.
  • the system of the invention is a metered dose system adapted to apply a dose of from about 0.45 to about 22.5 mg of active per unit dose.
  • the active agent is nicotine
  • the dose applied will more preferably be from about 0.9 to about 18 mg of nicotine per unit dose and most preferably from 10.9 to 16.2 mg of nicotine per unit dose.
  • the active agent is selegiline
  • the dose applied will more preferably be from about 2.7 to about 9 mg of selegiline per unit dose and most preferably from about 3.6 to about 7.2 mg of selegiline per unit dose.
  • the system will typically apply the dose over an area of skin of at least 5 cm 2 , preferably via a metered dose spray, and generally no more than about 100 cm 2 .
  • the dose will be applied over an area of skin of at least 20 cm 2 .
  • the solution used in the method of the invention will typically contain no more than 10% by weight of components other than volatile solvent and active, more preferably no more than 5% of other components still more preferably less than 1 % and most preferably is essentially free of other components. It is particularly preferred that the composition is free of dermal penetration enhancers such as those referred to in US Patent 6299900.
  • the solution comprises a volatile solvent.
  • the volatile solvent is present in an amount of from 75 to 99% by weight of the total composition; where the active agent is selegiline the volatile solvent is most preferably present in the mount of from 80 to 96% and where the active agent is nicotine the volatile solvent is most preferably about 80 to 90% by weight of the total solution.
  • volatile solvents examples include ethanol, isopropanol, ethyl acetate, chloroform and acetone.
  • volatile solvents examples include ethanol and isopropanol.
  • propellants such as hydrofluorocarbons, hydrocarbons, hydrochlorofluorocarbons and their mixtures may be used in aerosol delivery of the compositions.
  • suitable propellants include hydrofluorocarbons, hydrocarbons hydrochlorofluorocarbons and mixtures of two or more thereof.
  • the most preferred propellants are HFC134a and mixtures thereof.
  • the invention provides a system for non-occlusive transdermal delivery of a volatile active, preferably selected from Nicotine and Selegiline, to an area of skin comprising a container; within the container a solution containing the volatile active dissolved in a volatile solvent in a concentration in the range of from 0.5 to 25% by weight; an applicator nozzle for delivering a spray of the solution onto the skin; and preferably a nozzle housing about the nozzle (and optionally also housing the container); and preferably a spacer extending from the housing for placement against the skin to stabilize the nozzle in spaced relationship to the area of skin.
  • a volatile active preferably selected from Nicotine and Selegiline
  • the system of the invention may be in the form of an aerosol in a pressurized container with a propellant such as hydrofluorocarbons, hydrocarbons, hydrochlorofluorocarbons and their mixtures.
  • a propellant such as hydrofluorocarbons, hydrocarbons, hydrochlorofluorocarbons and their mixtures.
  • the container may be pressurized by priming to build pressure prior to the solution being dispensed or the container may be provided with a pump spray.
  • the system may comprise a pump pack for delivery of a spray from a container via a spray nozzle.
  • the system of the invention preferably uses a spacer such as the shroud extending from the housing for placement against the skin to stabilize the nozzle in spaced relationship to the area of skin.
  • the shroud preferably provides spacing from the skin of at least 1 cm and more preferably at least 2 cm and generally not more than 8cm and preferably not more than 5 cm.
  • One example of a preferred system in accordance with the invention utilizes a pump spray dispensing device of the type described in US Patent 6978945 the contents of which are herein incorporated by reference.
  • FIG. 1 is a side, elevational view of one form of dispensing device incorporating one embodiment of the present invention
  • FIG. 2 is a rear, elevational view of the device shown by FIG. 1
  • FIG. 3 is a side, elevational, cross-sectional view taken along line MINI of FIG. 2
  • FIG. 4 is a front, perspective, exploded view of the device shown by FIG. 3;
  • FIG. 5 is a side, elevational, cross-sectional view of the device shown in FIG. 3, but with a dust cap positioned over the outlet of the device;
  • FIG. 6 is a side, elevational view of the device shown in FIG. 5;
  • FIG. 7 is a graph showing the in-vitro human skin penetration of nicotine from formulations in isopropylalcohol.
  • FIG. 8 is a graph showing the in-vitro human skin penetration of selegiline from formulations in IPA.
  • the example of the dispensing device containing a composition for use in the inventioni is shown in the accompanying drawings and includes a hollow body 2 having a chamber 3 (FIG. 3) for receiving a substance capsule 4, which may be replaceable in some circumstances.
  • the contents (the substance) of the capsule 4 will be selected to suit the intended use of the device 1.
  • the capsule 4 includes a substance container 5 and a manually operable pump 6 (FIG. 3) for dispensing a metered quantity of the substance.
  • Other arrangements could be adopted, such as an aerosol- type dispenser, in which event a suitable control valve (not shown) would be provided within the upper part, or some other convenient part, of the capsule 4.
  • the substance stored in the container 5 includes selegiline or nicotine in a volatile solvent (preferably ethanol, isopropanol or a mixture of the two) in an amount of from 0.5 to 25% (preferably from 10 to 20% and most preferably from 12 to 18% where the active agent is nicotine; and preferably from 3 to 10% and most preferably from 4 to 8% where the active agent is selegiline) by weight of the solution.
  • a volatile solvent preferably ethanol, isopropanol or a mixture of the two
  • the solution composition contains no more than 1 % (and is preferably essentially free) of other components such as penetration enhancers, adhesives and film formers.
  • the total volume of liquid in the system will depend on the number of doses required, the concentration of the active and the volume dispersed and is typically in the range of from 1 to 50ml.
  • the solution of volatile active is driven to emerge from the device, it is preferably applied to a target area at relatively low volume levels.
  • the substance may be deposited in the range of 1 to 10 microliters per square centimeter of the target area.
  • the body 2 may be formed of two separable parts 2a and 2b. Those parts combine to form the chamber 3 when they are connected together as shown by FIGS. 1 and 6, and any suitable means may be adopted to releasably connect the two parts 2a and 2b.
  • pins 7 provided on the part 2a are adapted to fit within complementary holes 8 provided in the part 2b (FIG. 4). The pins 7 and the holes 8 cooperate in a manner such as to resist inadvertent separation of the parts 2a and 2b.
  • an actuator button 9 is movably mounted on the body 2 so as to be accessible at the upper end of the body 2 (FIGS. 1 , 5 and 6).
  • the button 9 cooperates with the pump 6 in a manner such that depression of the button 9 causes operation of the pump 6.
  • the pump 6 When the pump 6 is operated, a quantity of the volatile active solution is withdrawn from the container 5 and is expelled through an outlet nozzle 10 associated with the pump 6, possibly in the form of a spray.
  • the button 9 locates over the outlet nozzle 10 and has an opening 1 1 aligned with the outlet passage 12 of the nozzle 10 so as to allow egress of the substance being dispensed.
  • the pump 6 operates in a known manner to pressurize the contents of the volatile active solution container 5, and thereby force a metered quantity of the solution to be expelled through the nozzle 10.
  • a shroud 13, preferably of substantially conical form, may be connected to the side of the body 2 adjacent the nozzle 10.
  • the shroud 13 is arranged to surround the spray of volatile active solution emerging from the nozzle 10, and may serve to confine that spray so that all or most of the substance is deposited on the intended target area.
  • the shroud 13 is preferably non-vented as hereinbefore defined.
  • the shroud 13 may also function as a distance regulator. That is, the distance between the nozzle 10 and the outer edge 14 of the shroud 13 may substantially correspond to the ideal distance over which the substance should be sprayed on to the target area. Such distance regulation may be particularly useful in circumstance where the device is being used for transdermal application of a substance.
  • a protective cap 15 may be removably attached to the outer end of the shroud 13 so as to close the open mouth 16 (FIG. 3) of the shroud 13.
  • the cap 15 is removed when the pump 6 is to be operated, and is replaced when the pump 6 is not in use.
  • Any suitable means may be employed to enable releasable attachment of the cap 15.
  • One option is to provide for snap engagement between the cap 15 and the shroud 13.
  • a circumferential rib 17 or lugs formed on an inner surface of a side wall 21 of the cap 15 may snap engage with an external circumferential rib 19 formed on the shroud 13 (FIG. 3).
  • the dispensing device 1 is provided with means for closing the nozzle 10 when the device is not in use. Any suitable means may be used for that purpose.
  • the nozzle closure means includes a member 20 attached to the end wall 21 of the cap 15.
  • the member 20 is in the form of an elongated stem extending axially of the cap 15 in the same direction as the side wall 21.
  • the length of the member 20 is such as to enable the outer terminal end 22 to engage around and/or within the outlet of the nozzle 10 when the cap 15 is properly in place on the shroud 13.
  • the system of the invention preferably comprises a shroud defining an exit space from said hollow body for receiving said substance emerging from said outlet passage and the end of which is placed against the area of skin to define the administration area within the perimeter of the shroud.
  • the system of the invention may be adapted as a fixed dose or may be adapted to allow the user to modify the dose to be delivered.
  • the system may provide a metered dose of the solution of active. It is preferred that the unit dose delivered by the system of the invention is in the range of from 0.45 to 22.5 mg of volatile active particularly for nicotine or selegiline.
  • the invention provides a method of reducing a craving for cigarettes in a smoker comprising administering to an area of skin of the smoker a metered dose spray of a composition comprising in the range of from 5 to 25% (preferably from 10 to 20% and most preferably from 12 to 18%) by weight of nicotine in a volatile solvent (preferably selected from ethanol, isopropanol and mixtures thereof) wherein the metered dose contains in the range of from 0.9 to 22.5mg of nicotine, preferably from 5 to 18mg of nicotine and most preferably from 10.8 to 16.2 mg of nicotine.
  • a metered dose spray of a composition comprising in the range of from 5 to 25% (preferably from 10 to 20% and most preferably from 12 to 18%) by weight of nicotine in a volatile solvent (preferably selected from ethanol, isopropanol and mixtures thereof) wherein the metered dose contains in the range of from 0.9 to 22.5mg of nicotine, preferably from 5 to 18mg of nicotine and most preferably from 10.8 to 16.2 mg of nicotine.
  • the spray is preferably allowed to dry without occlusion such as with a patch plaster or other artificial applied physical barrier.
  • the invention may comprise administration of one or more metered doses during a day and preferably at least two sets of metered doses each set providing one or more metered dose spray applications and providing a total dosage in the range of from 10 to 32.5 mg of nicotine and spaced at least four hours and more preferably at least eight hours apart.
  • the invention further provides a method of treatment or prophylaxis of Parkinson's disease comprising administering to an area of skin of the subject suffering or in need of prophylaxis against Parkinson's disease a metered dose spray of a composition comprising in the range of from 0.5 to 10% (preferably from 3 to 10% and most preferably from 4 to 8%) by weight of selegiline in a volatile solvent (preferably selected from ethanol, isopropanol and mixtures thereof) wherein the metered dose contains in the range of from 0.45 to 20 mg of selegiline, preferably from 2.7 to 9 mg of selegiline and most preferably from 3.6 to 7.2 mg of selegiline.
  • the spray is preferably allowed to dry without occlusion such as with a patch plaster or other applied physical barrier.
  • the invention may comprise administration of one or more metered doses during a day and preferably only one metered dose per day, providing a single metered dose spray application and providing a total dosage in the range of from 0.45 to 15 mg of selegiline.
  • the invention provides the use of a volatile active and (particularly nicotine or selegiline) and a volatile solvent (particularly ethanol, isopropanol or a mixture thereof) in manufacture of a medicament composition for treatment of a disease (preferably selected from smoking addiction and Parkinson's disease) in a subject by application of a unit dose spray comprising from 0.45 to 22.5 mg to an area of skin of the subject wherein the composition comprises the volatile active dissolved in a volatile solvent in a concentration in the range of from 0.5 to 25% by weight of the composition.
  • a volatile active and particularly nicotine or selegiline
  • a volatile solvent particularly ethanol, isopropanol or a mixture thereof
  • This example examines the transdermal administration of Nicotine from a spray solution in a volatile alcohol.
  • compositions were prepared containing 1 1.1 and 16.7% nicotine in isopropanol by dissolving the appropriate amount of nicotine in the alcohol.
  • formulations will deliver 4.4, 6.8 and 13.6 mg of nicotine systemically if applied to human skin at time zero and time 8 hours after application.
  • the formulations may be modified to provide doses of 5, 10 and 15 mg for use clinically by using concentrations of about 12.6 % and 18.4% nicotine.
  • the most preferred anatomical application site is the inner forearm although a range of anatomical sites may be used such as the thigh, abdomen, outer arm, buttocks etc.
  • the administration may thus be made to provide 5, 10 and 15 mg of nicotine per 16 hours. These equate to the current delivery from single applications of transdermal patches. It may be preferred to apply the formulations twice a day at time zero hours and then eight hours later or when cigarette craving dictated other regimens in accordance with the known blood level effects of nicotine.
  • the differing doses can be achieved using formulations containing increasing amounts of nicotine.
  • This Example examines the transdermal administration of Selegiline from a spray solution in a volatile alcohol.
  • Selegiline is used as a treatment for Parkinson's disease as a monotherapy or in combination with levodopa.
  • the therapeutic daily dose of selegiline varies depending on the route of administration. Oral tablets are dosed at 5-10 mg per day whilst an orally dissolving formulation is dosed at 1.25 -2.5 mg.
  • the systemic dose for transdermal administration may be approximately 0.45 mg per spray with the applied number of sprays being one or two per day at a single dosing time or a single spray per day utilizing two different concentrations i.e. the daily systemic dose is 0.5 or 1 mg.
  • Formulations containing 10, 15 and 20% selegiline were prepared by dissolving the requisite amount of the drug in isopropyl alcohol.
  • FIG. 8 The pattern of delivery observed in FIG. 8 is actually quite unexpected and advantageous because there is no need to sustain delivery for the full 24 hour since selegiline is an irreversible inhibitor of monoamine oxidase (MAO) type B. Therefore sustained blood levels over a 24 hour period are not required and those delivered by a single dose of a profile such as that shown in FIG. 8 will rise and fall during that period.
  • MAO monoamine oxidase
  • compositions may be delivered from a metered dose spray system such as that described in US Patent 6978945.
  • phase I open label, two way cross-over study to determine the pharmacokinetics of nicotine following application of various nicotine spray formulations versus a commercially available nicotine patch (5mg).
  • Table 1 Study Treatments Investigated During a Human Clinical Trial
  • Table 2 Mean ⁇ SD Nicotine and Cotinine Pharmacokinetic Parameters Calculated For Study Treatments A, B, C and D. Values in brackets represent 5 the range between subjects.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Psychology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention porte sur un procédé d'administration transdermique d'un agent actif volatile, de préférence choisi parmi la Nicotine et la Sélégiline. Ce procédé comprend l'application à une zone de la peau d'une solution, de préférence sous forme de pulvérisation, contenant l'agent actif volatile dissous dans un solvant volatile dont la concentration se situe dans la plage de 0,5 à 25% en poids sans occlusion de la solution appliquée.
PCT/AU2008/000537 2007-04-20 2008-04-18 Procédé et système pour l'administration transdermique d'un agent actif volatil WO2008128280A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US91299507P 2007-04-20 2007-04-20
US60/912,995 2007-04-20

Publications (1)

Publication Number Publication Date
WO2008128280A1 true WO2008128280A1 (fr) 2008-10-30

Family

ID=39874976

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU2008/000537 WO2008128280A1 (fr) 2007-04-20 2008-04-18 Procédé et système pour l'administration transdermique d'un agent actif volatil

Country Status (1)

Country Link
WO (1) WO2008128280A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000045795A2 (fr) * 1999-02-05 2000-08-10 Cipla Limited Sprays topiques
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US6325990B1 (en) * 1995-10-20 2001-12-04 Laboratoire L. Lafon Film forming composition for spraying on the skin
US20040013620A1 (en) * 1996-02-19 2004-01-22 Monash University Transdermal delivery of antiparkinson agents
WO2005039531A1 (fr) * 2003-10-10 2005-05-06 Antares Pharma Ipl Ag Formulation pharmaceutique transdermique visant a reduire les residus sur la peau
US20070248658A1 (en) * 2005-12-23 2007-10-25 Ines Zurdo Schroeder Use of film-forming hair care polymers from the group of polyurethanes and pharmaceutical preparations and patches that contain these polymers

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6325990B1 (en) * 1995-10-20 2001-12-04 Laboratoire L. Lafon Film forming composition for spraying on the skin
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US20040013620A1 (en) * 1996-02-19 2004-01-22 Monash University Transdermal delivery of antiparkinson agents
WO2000045795A2 (fr) * 1999-02-05 2000-08-10 Cipla Limited Sprays topiques
WO2005039531A1 (fr) * 2003-10-10 2005-05-06 Antares Pharma Ipl Ag Formulation pharmaceutique transdermique visant a reduire les residus sur la peau
US20070248658A1 (en) * 2005-12-23 2007-10-25 Ines Zurdo Schroeder Use of film-forming hair care polymers from the group of polyurethanes and pharmaceutical preparations and patches that contain these polymers

Similar Documents

Publication Publication Date Title
US8689803B2 (en) Systems and methods for effecting cessation of tobacco use
JP3830158B2 (ja) 禁煙補助組成物
US20090004249A1 (en) Dual release nicotine formulations, and systems and methods for their use
US20080138399A1 (en) Dual release nicotine formulations, and systems and methods for their use
RU2572692C2 (ru) Сублингвальные композиции дексмедетомидина и способы их применения
IL205153A (en) Powder Compounds Containing Apomorphine and Magnesium Strat for the Treatment of Parkinson's Disease
WO2008069970A2 (fr) Formulations de nicotine, trousses, systèmes et procédés d'utilisation
WO2007070643A2 (fr) Compositions et procedes pour le traitement de conditions dermatologiques
US20240189378A1 (en) Oral care products
BRPI0707235A2 (pt) formulação de fentanil sublingual, dose unitária de uma formulação de fentanil sublingual, métodos para tratar dor e para tratar a manifestação súbita da dor, dispositivos de dose unitária ou dose dupla e de dose múltipla para a administração sublingual de um medicamento, método para preparar uma composição farmacêutica para a administração sublingual, formulação farmacêutica sublingual, dose unitária de uma formulação farmacêutica sublingual, e, método para tratar um paciente humano
MXPA04012041A (es) Una composicion liquida y regulada de nicotina para administracion pulmonar.
PL222060B1 (pl) Farmaceutyczne preparaty donosowe oraz sposoby ich stosowania
US20080138294A1 (en) Systems and methods for effecting cessation of tobacco use
EP2765989B1 (fr) Procédés et compositions pour administration rapide d'agents actifs par la bouche
Florence et al. Routes of Drug Administration: Topics in Pharmacy
AU2004273574B2 (en) Buccal formulations of galanthamine and uses thereof
WO2008128280A1 (fr) Procédé et système pour l'administration transdermique d'un agent actif volatil
EA007351B1 (ru) Фармацевтическая композиция для чрескожной доставки физиологически активных агентов
KR100469995B1 (ko) 천식치료제를 함유한 매트릭스형 패취
WO2011064769A1 (fr) Procédés et compositions pharmaceutiques pour le traitement des bouffées de chaleur
WO2021134029A1 (fr) Nicotine topique pour le sevrage tabagique
Mittal et al. Review on nasal drug delivery system
Mittal et al. World Journal of Pharmaceutical Sciences
Dugger III et al. Immediate-Immediate Release (I2R) Lingual or Buccal Spray Formulations for Transmucosal Delivery of Drug Substances
MXPA01011480A (es) Composiciones farmaceuticas que comprenden apocodeina y/o sus derivados.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08733364

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08733364

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载