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WO1996039136A1 - Formulation transdermique a base de ropinirole - Google Patents

Formulation transdermique a base de ropinirole Download PDF

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Publication number
WO1996039136A1
WO1996039136A1 PCT/EP1996/002435 EP9602435W WO9639136A1 WO 1996039136 A1 WO1996039136 A1 WO 1996039136A1 EP 9602435 W EP9602435 W EP 9602435W WO 9639136 A1 WO9639136 A1 WO 9639136A1
Authority
WO
WIPO (PCT)
Prior art keywords
ropinirole
transdermal
transdermal formulation
formulation
free base
Prior art date
Application number
PCT/EP1996/002435
Other languages
English (en)
Inventor
Anil Patel
Original Assignee
Smithkline Beecham Plc
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 Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to EP96917499A priority Critical patent/EP0831810A1/fr
Priority to JP9500145A priority patent/JPH11506462A/ja
Publication of WO1996039136A1 publication Critical patent/WO1996039136A1/fr

Links

Classifications

    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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

Definitions

  • the present invention relates to a transdermal formulation comprising 4-(2-di-n- proylaminoethyl)-2(3H)-indolone and for the use thereof in treating Parkinson's Disease.
  • EP 0 299 602- A2 further discloses that other forms of administration may be considered for ropinirole and salts thereof, including parenteral, rectal and transdermal.
  • a typical transdermal formulation is said to comprise a conventional aqueous or non-aqueous vehicle, for example, a cream, ointment lotion or paste in the form of a medicated plaster, patch or membrane. There is however no further guidance on suitable transdermal formulations or expected dosage for such formulations.
  • a transdermal formulation offers the advantage of a more convenient mode of administration of the drug substance, thereby potentially enhancing patient compliance.
  • drug substance is released in a more controlled fashion, over a prolonged period, offering potential therapeutic advantges.
  • transdermal formulations able to provide a therapeutically useful amount of the drug may be prepared by using the free base form of the compound, in comparison to the hydrochloride salt preferred for tablet formulation.
  • the present invention provides for a transdermal formulation comprising ropinirole (free base).
  • Such formulations offer not only a more convenient method of administration but also possible therapeutic benefits and improved side effect profile.
  • transdermal formulations are well known in the art (see for instance Percutaneous Absorption and Transdermal Therapy, K A Walters, March 1986; Pharmaceutical Dosage Forms and Drug Delivery Systems, (5th Ed.), H C. Ansel and N G. Popovich, Chapter 9, Lea and Febiger (1990), pages 307 to 320 and Sustained and Controlled Release Drug Delivery Systems, ed J R Robinson, Marcel Dekker Inc., New York (1978), pages 579 et seq.).
  • Two main types of transdermal delivery devices are currentiy marketed and these are classified as matrix and membrane systems (Physicochemical Principles of Pharmacy, A.T. Florence and D. Attwood, 2nd Edition, Macmillan, 1993, page 331).
  • the drug is dispersed in a release controlling matrix which consists either of a gel or an adhesive film.
  • Membrane systems generally consist of a drug reservoir, a rate-controlling membrane and an adhesive layer. In both cases the active is dissolved or suspended in a vehicle which then forms an integral part of the delivery device.
  • the drug substance may be dissolved or suspended in a liquid or a gel.
  • Suitable vehicles include both aqueous and non-aqueous vehicles, for instance saline and saline/propylene glycol (1:1).
  • a penetration enhancer may also be added, if appropriate.
  • the transdermal formulation is provided in the form of a medicated plaster, patch or membrane, preferably a patch.
  • the patch is between 10 and 50cm 2 , preferably between 20 and 40 cm 2 .
  • the patch will be provided with a pharmaceutically accetable adhesive layer so that it can retained on the skin of the user.
  • the adhesive effect of the layer will be reversible such that the patch will remain in place for the lifetime of the patch but still be easy for the Parkinson's Disease patient to apply and remove.
  • ropinirole free base may be generated in situ in the transdermal formulation, from a suitable ropinirole salt such as ropinirole hydrochloride, suitably immediately prior to use.
  • a suitable ropinirole salt such as ropinirole hydrochloride
  • this may be achieved by including in the formulation a base which would be brought into contact with the ropinirole salt to effect formation of the free base.
  • the salt and base are kept apart, to avoid premature reaction, for instance in a two compartment reservoir having a rupturable barrier between the two compartments.
  • a preliminary evaluation of transdermal candidates is performed prior to incorporation in such a device.
  • the most effective method is to determine drug penetration from suspensions or solutions using a human skin in vitro model, such as the Franz cell (Dematological Formulations: Percutaneous Abso ⁇ tion, B W Barry, Marcel Dekker (1983), page 245).
  • the delivery profile will provide a steady rate delivery.
  • a compartmentalised rate controlled device may be used.
  • a suitable target skin flux will be in the range 5 to 25, preferably 10 to 15 ⁇ g/cm 2 hr.
  • the amount of ropinirole administered through a transdermal formulauon according to the present invention will be selected so that it will provide an amount of ropinirole substantially similar to that obtained following conventional oral administration of a tablet formulation, that is substantially similar to that obtained following administration of between 0.1 and lOmg of ropinirole (expressed as the free base) three times a day, assuming about 50% bioavailablity.
  • the transdermal formulation is provided in unit dose form.
  • the transdermal formulation is provided in a range of dosage amounts, for instance to allow for titration of an individual patient's drug requirement.
  • a suitable dose may be obtained by combining different strength formulations.
  • the unit dose form will provide sufficient drug substance for a 24 hour period (including, if appropriate 'off time'), to permit once-a-day application of the formulation. Suitably such application may be in the evening.
  • the transdermal formulation will be administered for a period of continuous therapy.
  • Transdermal formulations according to the present invention will be of use in therapy, in particular treating Parkinson's Disease. Accordingly, in a further aspect, the present invention provides for the manufacture of a medicament comprising ropinirole (free base) adapted for a transdermal administration for use in treating Parkinson's Disease.
  • the transdermal formulation may be used in patients in all stages of disease and/or as therapy after initial dose titration with a conventional tablet.
  • Ropinirole hydrochloride (190gm), water (1.35L) and ammonia (160mL,SG 0.88) were added to a flask fitted with stirrer and nitrogen bleed. This mixture was then stirred at ambient for ca 2hours and then extracted with dichloromethane (lx500mL, lx 250mL, lx 200mL). All the organic extracts were combined, washed with brine (3x50mL) and dried over with magnesium sulphate (if free water was still present). Removal of the solvent by evaporation under reduced pressue gave a light brown solid (142gm, 85% yield).
  • a typical patch comprising a membrane is as follows:
  • a backing layer of aluminized plastic that is impermeable to ropinirole; drug reservoir containing ropinirole (30 to 60mg/ml) in a saline/propylene glycol (1:1) vehicle; ethylene- vinyl acetate copolymer membrane that is permeable to ropinirole; and a layer of hypoallergenic silicone adhesive; plus a protective peel strip covering the adhesive surface.
  • a typical patch comprising a matrix is as follows:
  • ropinirole as the free base
  • a ropinirole salt for formulation into a transdermal delivery system was initially evaluated by determining drug penetration from suspensions or solutions using a human skin in vitro model.
  • the in vitro percutaneous penetration method utilised saturated solutions of ropinirole hydrochloride and ropinirole free base.
  • the in vitro set up consisted of modified Franz cells (Dematological Formulations: Percutaneous Absorption. B.W. Barry, Marcel Dekker, 1983, 245) with full thickness human abdominal skin and a receptor of 0.9% saline.
  • the vehicles tested were ropinirole and its hydrochloride salt in aqueous 0.9% saline and aqueous 0.9% saline/propylene glycol (50:50). Samples were taken from the receptor at intervals and analysed for ropinirole content. From these results the concentration of ropinirole penetrating human skin with time could be determined.
  • Penetration of the free base appears to be 20 fold better than the salt from the 0.9% saline vehicle and 40 fold better from the PG: saline vehicle.

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

Abstract

Cette invention concerne des formulations transdermiques à base de ropinirole destinées à être utilisées dans le traitement de la maladie de Parkinson.
PCT/EP1996/002435 1995-06-06 1996-06-04 Formulation transdermique a base de ropinirole WO1996039136A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP96917499A EP0831810A1 (fr) 1995-06-06 1996-06-04 Formulation transdermique a base de ropinirole
JP9500145A JPH11506462A (ja) 1995-06-06 1996-06-04 ロピニロールを含有してなる経皮製剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9511366.8A GB9511366D0 (en) 1995-06-06 1995-06-06 Novel formulations
GB9511366.8 1995-06-06

Publications (1)

Publication Number Publication Date
WO1996039136A1 true WO1996039136A1 (fr) 1996-12-12

Family

ID=10775543

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/002435 WO1996039136A1 (fr) 1995-06-06 1996-06-04 Formulation transdermique a base de ropinirole

Country Status (4)

Country Link
EP (1) EP0831810A1 (fr)
JP (1) JPH11506462A (fr)
GB (1) GB9511366D0 (fr)
WO (1) WO1996039136A1 (fr)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19814084A1 (de) * 1998-03-30 1999-10-14 Lohmann Therapie Syst Lts D2-Agonist enthaltendes transdermales therapeutisches System zur Behandlung des Parkinson-Syndroms und Verfahren zu seiner Herstellung
WO2003011291A1 (fr) * 2001-07-30 2003-02-13 Hexal Ag Systeme therapeutique transdermique (reservoir tts) pour utiliser du pramipexol et du ropinirol
US7258871B2 (en) 2000-10-20 2007-08-21 Neurobiotec Gmbh Combination of a transdermal therapeutic system and an oral and/or parenteral preparation containing dopamine agonists for the treatment of dopaminergic disease states
WO2008005240A3 (fr) * 2006-06-29 2008-05-08 Jazz Pharmaceuticals Compositions pharmaceutiques de ropinirole et leurs méthodes d'application
WO2009082268A2 (fr) 2007-12-21 2009-07-02 Alla Chem, Llc Ligands dalpha-adrénorécepteurs, de récepteurs de dopamine, de l'histamine, d'imidazoline et de sérotonine ainsi que leurs procédés d'utilisation
WO2009112167A1 (fr) * 2008-03-11 2009-09-17 Lts Lohmann Therapie-Systeme Ag Système thérapeutique transdermique avec membrane stabilisée
WO2010024717A1 (fr) 2008-08-22 2010-03-04 Алла Xem, Ллс Ligand possédant une gamme étendue d’activité pharmacologique, composition pharmaceutique, médicament et méthode de traitement
EP2258355A1 (fr) * 2008-02-27 2010-12-08 Hisamitsu Pharmaceutical Co., Inc. Patch
US7927624B2 (en) 2000-04-14 2011-04-19 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
CN102361639A (zh) * 2009-04-24 2012-02-22 久光制药株式会社 内包贴附剂的包装袋、及贴附剂的保存方法
EP2438917A1 (fr) * 2009-05-21 2012-04-11 Hisamitsu Pharmaceutical Co., Inc. Préparation transdermique
WO2011132966A3 (fr) * 2010-04-23 2012-04-12 아이큐어(주) Préparation pour absorption transdermique
CN103561737A (zh) * 2011-05-31 2014-02-05 久光制药株式会社 含有罗匹尼罗的贴附剂及其包装体
US9155725B2 (en) 2008-02-27 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Adhesive skin patch and packaged product
US9155710B2 (en) 2011-05-31 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Ropinirole-containing patch and package thereof
US9186335B2 (en) 2002-07-30 2015-11-17 Ucb Pharma Gmbh Hot melt TTS for administering rotigotine
US9320728B2 (en) 2013-06-28 2016-04-26 Hisamitsu Pharmaceutical Co., Inc. Method for producing patch, patch and package
US9849095B2 (en) 2011-12-01 2017-12-26 Teikoku Seiyaku Co., Ltd. Ropinirole-containing adhesive patch
US10149834B2 (en) 2011-12-01 2018-12-11 Teikoku Seiyaku Co., Ltd. Ropinirole-containing adhesive patch
US10716763B2 (en) 2015-04-15 2020-07-21 Hisamitsu Pharmaceutical Co., Inc. Transdermal patch containing ropinirole
US20210169849A1 (en) * 2019-04-17 2021-06-10 Vici Health Sciences LLC Liquid pharmaceutical compositions

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10338174A1 (de) 2003-08-20 2005-03-24 Lts Lohmann Therapie-Systeme Ag Transdermale Arzneimittelzubereitungen mit Wirkstoffkombinationen zur Behandlung der Parkinson-Krankheit
WO2014084311A1 (fr) 2012-11-30 2014-06-05 帝國製薬株式会社 Patch adhésif contenant du ropinirole
JP6373061B2 (ja) * 2014-05-23 2018-08-15 帝國製薬株式会社 経皮投与製剤

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"FORMES PHARMACEUTIQUES NOUVELLES", 1988, LAVOISIER, PARIS, XP002013798 *
D.B. CALNE: "TREATMENT OF PARKINSON'S DISEASE", THE NEW ENGLAND JOURNAL OF MEDICINE, vol. 329, no. 14, 1993, pages 1021 - 1027, XP002013778 *
H.C. ANSEL ET AL.: "TRANSDERMAL DRUG DELIVERY SYSTEMS, OINTMENTS, CREAMS, LOTIONS, AND OTHER PREPARATIONS", PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS 5TH ED., CHAPTER 9, 1990, pages 307 - 320, XP002013779 *

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10322093B2 (en) 1998-03-30 2019-06-18 Ucb Biopharma Sprl Method for producing a transdermal therapeutic system which contains a D2 agonist
DE19814084A1 (de) * 1998-03-30 1999-10-14 Lohmann Therapie Syst Lts D2-Agonist enthaltendes transdermales therapeutisches System zur Behandlung des Parkinson-Syndroms und Verfahren zu seiner Herstellung
US6884434B1 (en) 1998-03-30 2005-04-26 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system which contains a d2 agonist and which is provided for treating parkinsonism, and a method for the production thereof
DE19814084B4 (de) * 1998-03-30 2005-12-22 Lts Lohmann Therapie-Systeme Ag D2-Agonist enthaltendes transdermales therapeutisches System zur Behandlung des Parkinson-Syndroms und Verfahren zu seiner Herstellung
US10251844B2 (en) 1998-03-30 2019-04-09 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system and method of use thereof for treating parkinsonism
US8303986B2 (en) 2000-04-14 2012-11-06 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
US7927624B2 (en) 2000-04-14 2011-04-19 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
US8460706B2 (en) 2000-04-14 2013-06-11 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
US7258871B2 (en) 2000-10-20 2007-08-21 Neurobiotec Gmbh Combination of a transdermal therapeutic system and an oral and/or parenteral preparation containing dopamine agonists for the treatment of dopaminergic disease states
WO2003011291A1 (fr) * 2001-07-30 2003-02-13 Hexal Ag Systeme therapeutique transdermique (reservoir tts) pour utiliser du pramipexol et du ropinirol
US9186335B2 (en) 2002-07-30 2015-11-17 Ucb Pharma Gmbh Hot melt TTS for administering rotigotine
WO2008005240A3 (fr) * 2006-06-29 2008-05-08 Jazz Pharmaceuticals Compositions pharmaceutiques de ropinirole et leurs méthodes d'application
WO2009082268A2 (fr) 2007-12-21 2009-07-02 Alla Chem, Llc Ligands dalpha-adrénorécepteurs, de récepteurs de dopamine, de l'histamine, d'imidazoline et de sérotonine ainsi que leurs procédés d'utilisation
US8871249B2 (en) 2008-02-27 2014-10-28 Hisamitso Pharmaceutical Co., Inc. Medicated patch
EP2258355A4 (fr) * 2008-02-27 2011-05-04 Hisamitsu Pharmaceutical Co Patch
US9155725B2 (en) 2008-02-27 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Adhesive skin patch and packaged product
EP2258355A1 (fr) * 2008-02-27 2010-12-08 Hisamitsu Pharmaceutical Co., Inc. Patch
US8580281B2 (en) 2008-02-27 2013-11-12 Hisamitsu Pharmaceutical Co., Inc. Medicated patch
US8882729B2 (en) 2008-03-11 2014-11-11 Lts Lohmann Therapie Systeme Ag Transdermal therapeutic system having stabilized membrane
WO2009112167A1 (fr) * 2008-03-11 2009-09-17 Lts Lohmann Therapie-Systeme Ag Système thérapeutique transdermique avec membrane stabilisée
WO2010024717A1 (fr) 2008-08-22 2010-03-04 Алла Xem, Ллс Ligand possédant une gamme étendue d’activité pharmacologique, composition pharmaceutique, médicament et méthode de traitement
CN102361639A (zh) * 2009-04-24 2012-02-22 久光制药株式会社 内包贴附剂的包装袋、及贴附剂的保存方法
EP2438917A4 (fr) * 2009-05-21 2014-01-22 Hisamitsu Pharmaceutical Co Préparation transdermique
US9238025B2 (en) 2009-05-21 2016-01-19 Hisamitsu Pharmaceutical Co., Inc. Transdermal preparation comprising a ropinirole derivative
EP2438917A1 (fr) * 2009-05-21 2012-04-11 Hisamitsu Pharmaceutical Co., Inc. Préparation transdermique
WO2011132966A3 (fr) * 2010-04-23 2012-04-12 아이큐어(주) Préparation pour absorption transdermique
CN103561737A (zh) * 2011-05-31 2014-02-05 久光制药株式会社 含有罗匹尼罗的贴附剂及其包装体
EP2716287A4 (fr) * 2011-05-31 2014-11-26 Hisamitsu Pharmaceutical Co Timbre transdermique adhésif contenant du ropinirole et produit emballé associé
US9918945B2 (en) 2011-05-31 2018-03-20 Hisamitsu Pharmaceutical Co., Inc. Ropinirole-containing patch and package thereof
US9155710B2 (en) 2011-05-31 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Ropinirole-containing patch and package thereof
EP2716287A1 (fr) * 2011-05-31 2014-04-09 Hisamitsu Pharmaceutical Co., Inc. Timbre transdermique adhésif contenant du ropinirole et produit emballé associé
US9849095B2 (en) 2011-12-01 2017-12-26 Teikoku Seiyaku Co., Ltd. Ropinirole-containing adhesive patch
US10149834B2 (en) 2011-12-01 2018-12-11 Teikoku Seiyaku Co., Ltd. Ropinirole-containing adhesive patch
US9320728B2 (en) 2013-06-28 2016-04-26 Hisamitsu Pharmaceutical Co., Inc. Method for producing patch, patch and package
US10716763B2 (en) 2015-04-15 2020-07-21 Hisamitsu Pharmaceutical Co., Inc. Transdermal patch containing ropinirole
US20210169849A1 (en) * 2019-04-17 2021-06-10 Vici Health Sciences LLC Liquid pharmaceutical compositions

Also Published As

Publication number Publication date
EP0831810A1 (fr) 1998-04-01
JPH11506462A (ja) 1999-06-08
GB9511366D0 (en) 1995-08-02

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