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WO1993014727A1 - Administration transcutanee de buprenorphine sous forme de complexes de paires d'ion - Google Patents

Administration transcutanee de buprenorphine sous forme de complexes de paires d'ion Download PDF

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Publication number
WO1993014727A1
WO1993014727A1 PCT/US1993/000733 US9300733W WO9314727A1 WO 1993014727 A1 WO1993014727 A1 WO 1993014727A1 US 9300733 W US9300733 W US 9300733W WO 9314727 A1 WO9314727 A1 WO 9314727A1
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WO
WIPO (PCT)
Prior art keywords
buprenorphine
ion pair
complex
pair complex
group
Prior art date
Application number
PCT/US1993/000733
Other languages
English (en)
Inventor
Eric J. Roos
Chia-Ming Chiang
Gordon L. Flynn
Kuldeepak Sharma
Original Assignee
Cygnus Therapeutic Systems
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 Cygnus Therapeutic Systems filed Critical Cygnus Therapeutic Systems
Publication of WO1993014727A1 publication Critical patent/WO1993014727A1/fr

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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
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/541—Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent

Definitions

  • This invention relates to the transdermal administration of effective dose levels of buprenorphine to patients. More particularly, it relates to a transdermal dosage form of buprenorphine as a buprenorphine ion pair complex and to its use.
  • Buprenorphine is the common name for (5 ⁇ ,7c_ (s) )-17-(cyclopropylmethyl)- ⁇ -(1,1-dimethylethyl)-4,5- epoxy-18,19-dihydro-3-hydroxy-6-methoxy- ⁇ -methyl-6,14-
  • buprenorphine has been ft. 35 administered most commonly by intramuscular injection or intravenous injection as reported by Norwich Eaton Pharmaceuticals, Inc., in "Buprenex Prescribing Information,” Norwich, N.Y., 1986; “Buprenex Compatibility Chart,” Norwich, N.Y., 1986; and “Buprenex: Background Data for Review for Pharmacy and Therapeutic Committees,” Norwich, N.Y., May 1985. See also, Heel, R.C., et al. , “Buprenorphine: A Review of Its Pharmacological Properties and Therapeutic Efficacy," Drugs (1979) 17;81-110.
  • 0432945 (Warner Lambert Company, published 19 June 1991), and European Patent Application No. 0430019.
  • European Patent Application No. 0368406 (Norwich Eaton Pharmaceuticals, Inc., published 16 May 1990) is directed to the transdermal delivery of buprenorphine in a carrier comprising a polar lower alkyl diol or triol solvent and a polar lipid that is a fatty alcohol ester, fatty acid ester, or mixture thereof.
  • PCT Patent Application No. W088/09676 is directed to the transdermal delivery of buprenorphine in a carrier comprising a polar lower alkyl diol or triol solvent and a polar lipid that is a fatty alcohol ester, fatty acid ester, or mixture thereof.
  • this invention provides a buprenorphine ion pair complex comprising a buprenorphine cation and an acid anion having the formula R-M", wherein M" is a negatively charged moiety such as carboxy, sulfate, sulfite, nitrate, nitrite, phosphate and phosphite; and R is linear or branched, substituted or unsubstituted, saturated or mono-, di- or tri-unsaturated alkyl having from about 5 to 20 carbon atoms and substituted or unsubstituted aryl, arylalkyl or phenyl, and the complex is formed by crystallization from a polar/non-polar solvent mixture.
  • M is a negatively charged moiety such as carboxy, sulfate, sulfite, nitrate, nitrite, phosphate and phosphite
  • R is linear or branched, substituted or unsubstituted, saturated or mono
  • a method of buprenorphine therapy for an individual is provided by administering a therapeutically effective amount of a buprenorphine ion pair complex comprising a buprenorphine cation and an acid anion having the formula R-M " , wherein M " is a negatively charged moiety such as carboxy, sulfate, sulfite, nitrate, nitrite, phosphate and phosphite; and R is linear or branched, substituted or unsubstituted, saturated or mono-, di- or tri-unsaturated alkyl having from about 5 to 20 carbon atoms and substituted or unsubstituted aryl, arylalkyl or phenyl to the individual transdermally.
  • M is a negatively charged moiety such as carboxy, sulfate, sulfite, nitrate, nitrite, phosphate and phosphite
  • R is linear or branched, substituted or un
  • This method can take the form of applying buprenorphine to a predetermined area of the patient's, skin adequate to enable the buprenorphine to permeate the area of skin at a rate in excess of about 40 micrograms per hour.
  • a laminated composite for administering the buprenorphine ion pair complex to an individual transdermally through a predetermined area of skin comprising a backing layer that is substantially impermeable to the passage of the buprenorphine ion pair complex; and, a reservoir layer comprising a pressure-sensitive adhesive polymer which contains a buprenorphine ion pair complex.
  • the basal surface of the reservoir layer is adapted to be adhered to said area of skin.
  • the administration is accomplished by affixing to the patient's skin the composite, which has a contact area with the patient's skin of from 10 to 100 cm 2 and which makes buprenorphine available to the area of skin for transdermal administration at a rate in excess of 0.05 micrograms per cm 2 per hour.
  • Preferred administration rates are from about 0.05 to about 5.0 micrograms per cm 2 per hour.
  • the drawing shows in cross-section an embodiment of a skin patch for transdermal administration of a buprenorphine ion pair complex.
  • Binrphine shall mean (5 ⁇ ,7 ⁇ (s))-17- (cyclopropylmethyl)- ⁇ -(1,1-dimethylethyl)-4,5-epoxy- 18,19-dihydro-3-hydroxy-6-methoxy- ⁇ -methyl-6,14- ethenomorphinan-7-methanol.
  • the term encompasses the free base and acid addition salts such as the hydrochloride.
  • Poration enhancement or “permeation enhancement” as used herein relates to an increase in the permeability of skin to a buprenorphine pharmacologically active agent, i.e., so as to increase the rate at which buprenorphine permeates into and through the skin.
  • a “permeation enhancer” is a material which achieves permeation enhancement of buprenorphine.
  • Poration enhancement or “permeation enhancement” refers to increased permeability to buprenorphine in the form in which it crosses the skin. This enhancement in the rate of delivery of a drug can result from chemical enhancement or skin enhancement.
  • Chemical enhancement refers to modifications to the drug that increases its partitioning into the skin or stratum corneum, often effected by an enhancing agent.
  • Skin enhancement refers to changes in skin structure that increases the diffusion of a drug across the skin. The mechanism by which the buprenorphine ion pair complex penetrates or permeates the skin is not known with certainty. However, without intending to limit the invention in any way, it is believed that buprenorphine crosses the stratum corneum as an ion pair complex, and at a later time dissociates into uncomplexed buprenorphine.
  • Transdermal (or “percutaneous) shall mean passage of a material into and through the skin to achieve effective therapeutic blood levels or deep tissue therapeutic levels. Transdermal delivery is to be distinguished from “topical” delivery.
  • Topical administration is meant local administration of a topical pharmacologically active agent to the skin as in, for example, the treatment of various skin disorders or the administration of a local anaesthetic.
  • Topical delivery intends penetration of a drug into the skin but not through it, i.e., topical administration does not intend actual passage of a drug into the bloodstream.
  • Carriers or “vehicles” as used herein refer to pharmaceutically acceptable carrier materials without pharmacological activity which are suitable for administration with other pharmaceutically active materials, and include any such materials known in the art, e.g., any liquid, gel, solvent, liquid diluent, solubilizer, or the like, which is nontoxic and which does not interact with the drug to be administered in a deleterious manner.
  • suitable carriers for use herein include non-aqueous materials such as mineral oil, silicone, inorganic gels, glycols and polyols, liquid sugars, waxes, petroleum jelly, and a variety of other oils and polymeric materials.
  • a “therapeutically effective” amount of buprenorphine is meant a nontoxic but sufficient amount of uncomplexed buprenorphine to provide the desired therapeutic effect.
  • the desired therapeutic effect is the alleviation of pain or inducement of analgesia in the patient or in the case of heroin or cocaine addicts, the achievement of detoxification.
  • the present invention involves the transdermal administration of buprenorphine as a low- melting, hydrophobic ion pair complex.
  • a "buprenorphine ion pair complex” refers to a complex formed by a buprenorphine cation (protonated at the basic nitrogen) and a hydrophobic organic anion.
  • the buprenorphine ion pair complex fully or partially dissociates in aqueous solution. However, the complex dissolves in non-aqueous solvents, the ion pair remaining together and undissociated.
  • opioid as used herein means any natural or synthetic opioid analgesic, such as morphine, oxymorphone, fentanyl, sufentanil, meperidine, propoxyphene, or oxycodone; any natural or synthetic narcotic antagonist such as nalmefene, naloxone or naltrexone; any natural or synthetic mixed opioid agonist/antagonist such as nalbuphine, butorphanol, buprenorphine or pentazocine.
  • opioid analgesic such as morphine, oxymorphone, fentanyl, sufentanil, meperidine, propoxyphene, or oxycodone
  • any natural or synthetic narcotic antagonist such as nalmefene, naloxone or naltrexone
  • any natural or synthetic mixed opioid agonist/antagonist such as nalbuphine, butorphanol, buprenorphine or pentazocine.
  • the buprenorphine ion pair complex has two components — a buprenorphine cation and an acid anion.
  • the buprenorphine cation is protonated at the N-17 amine site.
  • the acid anion is generally a fatty acid anion or aromatic acid anion.
  • the acid anion of the invention is an acid anion having the formula R-MT, wherein M * is a negatively charged moiety selected from the group consisting of carboxy, sulfate, sulfite, nitrate, nitrite, phosphate and phosphite; and wherein R is selected from the group consisting of linear or branched, substituted or unsubstituted, saturated or mono-, di- or tri-unsaturated alkyl having from about 5 to 20 carbon atoms and substituted or unsubstituted aryl, arylalkyl or phenyl.
  • the substitutions include neutral, positively charged, and negatively charged substitutions.
  • Neutral substitutions include hydroxy, alkoxy, halo (fluoro, chloro, bromo, iodo) , nitro, formyl, keto, alkanoyl, amido, and imido groups.
  • Positively charged substitutions include amino, diazo and guanido groups.
  • Negatively charged groups include carboxy, sulfate, sulfite, nitrate, nitrite, tosylate, brosylate, mesylate, phosphate, phosphite, and selenate groups.
  • M " is carboxy and R is unsubstituted or halo-substituted, branched or linear alkyl.
  • the buprenorphine ion pair complex is easily formed by crystallizing the cation and anion together from a solvent mixture comprising a non-aqueous polar and a nonpolar solvent.
  • a solvent mixture comprising a non-aqueous polar and a nonpolar solvent.
  • the buprenorphine and acid are added as free buprenorphine base and protonated acid, and the cation and anion are formed in solution. Any solvent mixture that solubilizes the buprenorphine cation and acid anion is acceptable. In such a nonaqueous solvent, the ion pair complex will not ionize.
  • a preferred solvent mixture is ethanol:hexane, more preferably in a 1:5 (v/v) ratio.
  • the solution from which the buprenorphine ion pair complex is crystallized will contain the buprenorphine cation and acid anion in molar ratios ranging from about 5:1 (cation:anion) to about 1:100. More preferably, the molar ratio is between about 1:1 and 1:3.
  • the buprenorphine ion pair complex is crystallized from the solvent mixture, it is at least partially redissolved in a nonaqueous solvent, where the ion pair remains complexed.
  • the solvent is a glycol such as propylene glycol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether or Softigen 767, an ester of the formula
  • n R' wherein m is an integer from 8 to 16, n is 1 or 2 and R' is lower alkyl, ethylene glycol, propylene glycol, or mixtures thereof.
  • the solvent is propylene glycol onolaurate (PGML) or propylene glycol (PG) .
  • PGML propylene glycol onolaurate
  • PG propylene glycol
  • a representative laminated composite for administering buprenorphine transdermally to humans to induce analgesia is shown in the drawing.
  • This composite generally designated 10, comprises a backing lamina 11, a buprenorphine reservoir lamina 12, and a release liner lamina 13.
  • the backing layer provides a protective covering for the composite and may itself be a single layer or a multiplicity of layers. For instance if the composite is to be worn for periods in excess of a day or two, it is desirable to make the backing from an elastomeric polymer such as polyurethane, polyether amide, or copolyester. In order to insure the occlusiveness of such elastomeric polymers, it may be necessary to place a layer of an occlusive material, such as polyisobutylene, between the backing and the reservoir. For devices that are intended to be worn for shorter durations, the backing may be made from relatively flexible but not elastomeric occlusive polymers such as polyester, polyethylene, or polypropylene. The thickness of the backing layer will normally be in the range of about 15 microns to about 250 microns.
  • the reservoir lamina is composed, it its most elementary form, of the buprenorphine ion pair complex in the amount of 1 to 12% by weight (preferably 2 to 10% by weight) and a pressure- sensitive adhesive.
  • the pressure-sensitive adhesive is generally a material such as an isobutylene, a silicone, or an aerylate adhesive.
  • Representative adhesives include: polyisobutylene; silicone adhesives such as silastic, Dow Corning X7-2920 silicone adhesive or Dow Corning 2675 silicone adhesive, with or without added silicone-oil tackifier; and non ⁇ aqueous solvent-based acrylate materials. Acrylate copolymer materials are available commercially.
  • Monsanto Chemical Company distributes a family of vinyl acetate-acrylate copolymer resin solutions under the trademarks GELVA® 737 and GELVA® 788 and Morton Thiokol, Inc. distributes acrylate copolymers under the trademarks Morstik 207A and Morstik 607.
  • acrylate copolymer materials can be used separately or in mixtures.
  • Several specific materials which give good results are the Morstik 607 materials, the GELVA® materials, which are believed to be based on 2-ethylhexyl acrylate, and mixtures of from about 20:1 to about 1:1 GELVA® 737 and GELVA® 788 (ratios given as weight ratios of GELVA® 737 to GELVA® 788) . All of these materials are solvent based but form films following casting and removal of the solvent.
  • the term “solid” is used broadly since the "solid” product is generally a tacky, amorphous (i.e. pressure sensitive adhesive) non-flowing material.
  • These matrix materials have the property of being high tack pressure-sensitive adhesives when dried and/or cured. Thus, the matrices formed from these materials can adhere directly to the patient's skin without the need for additional separate adhesives.
  • propylene glycol monolaurate is intended to encompass the pure compound as well as the mixture that is sold commercially. It is also intended that the enhancer may be composed of a mixture of said esters, by themselves or in combination, with one or both of the mentioned ethers.
  • Particularly preferred enhancers are the vegetable oils, which are fatty acid esters that may also contain some free fatty acid.
  • Vegetable oils of this invention include corn oil, sesame oil, peanut oil, coconut oil, soybean oil, almond oil, olive oil and mixtures thereof.
  • the thickness of the reservoir layer will normally be in the range of 20 microns to 150 microns, preferably 25 microns to 100 microns.
  • the reservoir lamina plays two functional roles, namely, it is a reservoir for the buprenorphine ion pair complex and the solvent/enhancer, and because of its composition, it is adhesive and its basal surface provides the means by which the composite is affixed to the skin.
  • the basal release liner lamina 13 is a protective coating for the reservoir lamina during storage and prior to affixation to the skin. This layer is removed from the composite before the composite is affixed to the skin.
  • the reservoir layer may be formulated by conventional methods known in the field of transdermal drug delivery devices and the three layers assembled into a laminated composite by like methods. These methods and specific embodiments of the invention are further illustrated by the following Experimental Results and Examples. These examples are not intended to limit the invention in any manner.
  • the rhombic shaped crystalline product was then filtered and dried under a gentle stream of nitrogen.
  • the purity of the base was checked by melting point and HPLC assay.
  • the melting point of the base was 210°C, virtually the same as reported in the literature.
  • the purity of the base by HPLC assay was 99%.
  • a buprenorphine ion pair complex was formed by dissolving free buprenorphine base and the appropriate acid (e.g., capric, myristic, lauric) in a mixture of 5:1 hexane ethanol. The solvent was then evaporated and the remaining substance was recovered as the complex.
  • the appropriate acid e.g., capric, myristic, lauric
  • J A x P x ⁇ C dt
  • P the permeability coefficient
  • ⁇ C the concentration gradient across the membrane, which is assumed to be the same as donor concentration.
  • the skin flux was determined from the slope of the plot of cumulative amount of buprenorphine permeated (M) versus time (t) .
  • Desired delivery rate 1.9 to 2.7 ⁇ g/cm 2 /h from 20 cm 2 patch
  • the percentages of base to fatty acid express a 1:2 molar ratio.
  • the percentages of buprenorphine to fatty acid express a 1:2 molar ratio.

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  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
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Abstract

Procédé et composite stratifié d'administration de buprénorphine sous forme d'un complexe d'ions par voie trancutanée afin de traiter la douleur. Le complexe de paires d'ions de buprénorphine est composé d'un cation de buprénorphine et d'un anion d'acide de la formule R-M- dans laquelle M- représente une fraction chargée négativement telle que carboxy, sulfate, nitrate, nitrite, phosphate et phosphite et R représente un alkyle linéaire ou ramifié, substitué ou non substitué, saturé ou mono-, di- ou tri-insaturé, ayant de 5 à 20 atomes de carbone et de l'aryle, de l'arylalkyle ou du phényle substitué ou non substitué, et est formé par cristallisation à partir d'un mélange de solvants polaires/non polaires. Ledit composite (10) comporte une couche de support (11) imperméable, une couche réservoir (12) qui contient le complexe d'ions de buprénorphine, et éventuellement un agent favorisant la pénétration combiné à un adhésif autocollant, les quantités de buprénorphine et d'un éventuel agent favorisant la pénétration étant ssuffisantes pour que la buprénorphine traverse la peau à un rythme supérieur à environ 0,05 νg/cm2/h. Ledit composite comporte également une couche de protection détachable (13).
PCT/US1993/000733 1992-01-31 1993-01-27 Administration transcutanee de buprenorphine sous forme de complexes de paires d'ion WO1993014727A1 (fr)

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001076608A1 (fr) * 2000-04-07 2001-10-18 Schering Aktiengesellschaft Compositions pouvant etre utilisees comme promoteurs de penetration dans des formulations transdermiques pour des ingredients a forte activite lipophile
US7309497B2 (en) 2000-08-24 2007-12-18 Schwarz Pharma Ag Injectable pharmaceutical composition for systematic administration of pharmacologically active ingredients
US7632859B2 (en) 2002-12-02 2009-12-15 Schwarz Pharma Ag Iontophoretic delivery of rotigotine for the treatment of Parkinson's disease
US8246980B2 (en) 2002-07-30 2012-08-21 Ucb Pharma Gmbh Transdermal delivery system
US8246979B2 (en) 2002-07-30 2012-08-21 Ucb Pharma Gmbh Transdermal delivery system for the administration of rotigotine
US8545872B2 (en) 2002-12-30 2013-10-01 Ucb Pharma Gmbh Device for the transdermal administration of a rotigotine base
US9186335B2 (en) 2002-07-30 2015-11-17 Ucb Pharma Gmbh Hot melt TTS for administering rotigotine
US10251844B2 (en) 1998-03-30 2019-04-09 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system and method of use thereof for treating parkinsonism
CN110441302A (zh) * 2018-05-03 2019-11-12 中国医学科学院药物研究所 一种妥洛特罗透皮贴剂无损质量控制方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4464378A (en) * 1981-04-28 1984-08-07 University Of Kentucky Research Foundation Method of administering narcotic antagonists and analgesics and novel dosage forms containing same
US4626539A (en) * 1984-08-10 1986-12-02 E. I. Dupont De Nemours And Company Trandermal delivery of opioids
US4806341A (en) * 1985-02-25 1989-02-21 Rutgers, The State University Of New Jersey Transdermal absorption dosage unit for narcotic analgesics and antagonists and process for administration
US4956171A (en) * 1989-07-21 1990-09-11 Paco Pharmaceutical Services, Inc. Transdermal drug delivery using a dual permeation enhancer and method of performing the same
US5026556A (en) * 1988-11-10 1991-06-25 Norwich Eaton Pharmaceuticals, Inc. Compositions for the transdermal delivery of pharmaceutical actives
US5069909A (en) * 1990-06-20 1991-12-03 Cygnus Therapeutic Systems Transdermal administration of buprenorphine

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4464378A (en) * 1981-04-28 1984-08-07 University Of Kentucky Research Foundation Method of administering narcotic antagonists and analgesics and novel dosage forms containing same
US4626539A (en) * 1984-08-10 1986-12-02 E. I. Dupont De Nemours And Company Trandermal delivery of opioids
US4806341A (en) * 1985-02-25 1989-02-21 Rutgers, The State University Of New Jersey Transdermal absorption dosage unit for narcotic analgesics and antagonists and process for administration
US5026556A (en) * 1988-11-10 1991-06-25 Norwich Eaton Pharmaceuticals, Inc. Compositions for the transdermal delivery of pharmaceutical actives
US4956171A (en) * 1989-07-21 1990-09-11 Paco Pharmaceutical Services, Inc. Transdermal drug delivery using a dual permeation enhancer and method of performing the same
US5069909A (en) * 1990-06-20 1991-12-03 Cygnus Therapeutic Systems Transdermal administration of buprenorphine

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10251844B2 (en) 1998-03-30 2019-04-09 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system and method of use thereof for treating parkinsonism
US10322093B2 (en) 1998-03-30 2019-06-18 Ucb Biopharma Sprl Method for producing a transdermal therapeutic system which contains a D2 agonist
WO2001076608A1 (fr) * 2000-04-07 2001-10-18 Schering Aktiengesellschaft Compositions pouvant etre utilisees comme promoteurs de penetration dans des formulations transdermiques pour des ingredients a forte activite lipophile
US7309497B2 (en) 2000-08-24 2007-12-18 Schwarz Pharma Ag Injectable pharmaceutical composition for systematic administration of pharmacologically active ingredients
US8246980B2 (en) 2002-07-30 2012-08-21 Ucb Pharma Gmbh Transdermal delivery system
US8246979B2 (en) 2002-07-30 2012-08-21 Ucb Pharma Gmbh Transdermal delivery system for the administration of rotigotine
US9186335B2 (en) 2002-07-30 2015-11-17 Ucb Pharma Gmbh Hot melt TTS for administering rotigotine
US7632859B2 (en) 2002-12-02 2009-12-15 Schwarz Pharma Ag Iontophoretic delivery of rotigotine for the treatment of Parkinson's disease
US8545872B2 (en) 2002-12-30 2013-10-01 Ucb Pharma Gmbh Device for the transdermal administration of a rotigotine base
CN110441302A (zh) * 2018-05-03 2019-11-12 中国医学科学院药物研究所 一种妥洛特罗透皮贴剂无损质量控制方法

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