CL2014000361A1 - Forma de dosificacion farmaceutica oral resistente a rompimiento de al menos 300n comprendiendo agonista opioide, antagonista opioide y un oxido de polialquileno de pm 200.000 g/mol - Google Patents

Forma de dosificacion farmaceutica oral resistente a rompimiento de al menos 300n comprendiendo agonista opioide, antagonista opioide y un oxido de polialquileno de pm 200.000 g/mol

Info

Publication number
CL2014000361A1
CL2014000361A1 CL2014000361A CL2014000361A CL2014000361A1 CL 2014000361 A1 CL2014000361 A1 CL 2014000361A1 CL 2014000361 A CL2014000361 A CL 2014000361A CL 2014000361 A CL2014000361 A CL 2014000361A CL 2014000361 A1 CL2014000361 A1 CL 2014000361A1
Authority
CL
Chile
Prior art keywords
opioid
mol
break
dosage form
pharmaceutical dosage
Prior art date
Application number
CL2014000361A
Other languages
English (en)
Inventor
Lutz Barnscheid
Anja Geissler
Original Assignee
Gruenenthal Chemie
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=47018994&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CL2014000361(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gruenenthal Chemie filed Critical Gruenenthal Chemie
Publication of CL2014000361A1 publication Critical patent/CL2014000361A1/es

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/485Morphinan derivatives, e.g. morphine, codeine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2095Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Neurosurgery (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CL2014000361A 2011-10-06 2014-02-13 Forma de dosificacion farmaceutica oral resistente a rompimiento de al menos 300n comprendiendo agonista opioide, antagonista opioide y un oxido de polialquileno de pm 200.000 g/mol CL2014000361A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11008131 2011-10-06
EP11009090 2011-11-16
EP12001297 2012-02-28

Publications (1)

Publication Number Publication Date
CL2014000361A1 true CL2014000361A1 (es) 2014-06-20

Family

ID=47018994

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2014000361A CL2014000361A1 (es) 2011-10-06 2014-02-13 Forma de dosificacion farmaceutica oral resistente a rompimiento de al menos 300n comprendiendo agonista opioide, antagonista opioide y un oxido de polialquileno de pm 200.000 g/mol

Country Status (18)

Country Link
US (1) US20130090349A1 (es)
EP (1) EP2763664A2 (es)
JP (1) JP2014528437A (es)
KR (1) KR20140075704A (es)
CN (1) CN103998025A (es)
AR (1) AR088250A1 (es)
AU (1) AU2012320496C1 (es)
BR (1) BR112014008120A2 (es)
CA (1) CA2850853A1 (es)
CL (1) CL2014000361A1 (es)
CO (1) CO6950467A2 (es)
EA (1) EA029508B1 (es)
EC (1) ECSP14013269A (es)
HK (1) HK1200741A1 (es)
IL (1) IL230819A0 (es)
MX (1) MX2014003973A (es)
PE (1) PE20141171A1 (es)
WO (1) WO2013050539A2 (es)

Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003024430A1 (en) 2001-09-21 2003-03-27 Egalet A/S Morphine polymer release system
WO2003024429A1 (en) 2001-09-21 2003-03-27 Egalet A/S Polymer release system
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
EP2301526B1 (en) 2003-03-26 2016-03-23 Egalet Ltd. Morphine controlled release system
DE10336400A1 (de) 2003-08-06 2005-03-24 Grünenthal GmbH Gegen Missbrauch gesicherte Darreichungsform
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE102005005446A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Bruchfeste Darreichungsformen mit retardierter Freisetzung
DE10361596A1 (de) 2003-12-24 2005-09-29 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102004032049A1 (de) 2004-07-01 2006-01-19 Grünenthal GmbH Gegen Missbrauch gesicherte, orale Darreichungsform
DE102005005449A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
NZ580972A (en) 2007-06-04 2012-02-24 Egalet Ltd Controlled release pharmaceutical compositions for prolonged effect
TWI454288B (zh) 2008-01-25 2014-10-01 Gruenenthal Chemie 藥物劑型
PT2273983T (pt) 2008-05-09 2016-10-28 Gruenenthal Gmbh Processo para a preparação de uma formulação em pó intermediária e uma forma de dosagem sólida final sob utilização de uma etapa de congelamento por atomização
WO2010089132A1 (en) 2009-02-06 2010-08-12 Egalet A/S Immediate release composition resistant to abuse by intake of alcohol
WO2010149169A2 (en) 2009-06-24 2010-12-29 Egalet A/S Controlled release formulations
CN102573805A (zh) 2009-07-22 2012-07-11 格吕伦塔尔有限公司 热熔挤出的控制释放剂型
ES2560210T3 (es) * 2009-07-22 2016-02-17 Grünenthal GmbH Forma de dosificación resistente a la manipulación para opiádes sensibles a la oxidación
EP2568968B1 (en) 2010-05-10 2017-07-12 Euro-Celtique S.A. Manufacturing of active-free granules and tablets comprising the same
US9901540B2 (en) 2010-05-10 2018-02-27 Euro-Celtique S.A. Combination of active loaded granules with additional actives
TWI516286B (zh) 2010-09-02 2016-01-11 歌林達股份有限公司 含陰離子聚合物之抗破碎劑型
RU2604676C2 (ru) 2010-09-02 2016-12-10 Грюненталь Гмбх Устойчивая к разрушению лекарственная форма, содержащая неорганическую соль
LT2736495T (lt) 2011-07-29 2017-11-10 Grünenthal GmbH Sugadinimui atspari tabletė, pasižyminti greitu vaisto atpalaidavimu
CN103857386A (zh) 2011-07-29 2014-06-11 格吕伦塔尔有限公司 提供药物立即释放的抗破碎片剂
MX349725B (es) * 2011-11-17 2017-08-10 Gruenenthal Gmbh Forma de dosificacion farmaceutica oral a prueba de manipulacion que comprende un agente antagonista y/o aversivo opioide, oxido de polialquileno y un polimero anionico.
JP6117249B2 (ja) 2012-02-28 2017-04-19 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 薬理学的に活性な化合物および陰イオン性ポリマーを含むタンパーレジスタント剤形
CA2868142A1 (en) 2012-04-18 2013-10-24 Grunenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
MX2014015880A (es) 2012-07-06 2015-08-05 Egalet Ltd Composiciones farmaceuticas disuasivas de abuso para liberacion controlada.
CA2795324C (en) * 2012-11-09 2015-07-14 Purdue Pharma Pharmaceutical compositions comprising hydromorphone and naloxone
US9737490B2 (en) 2013-05-29 2017-08-22 Grünenthal GmbH Tamper resistant dosage form with bimodal release profile
JP6445537B2 (ja) * 2013-05-29 2018-12-26 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 1個または複数の粒子を含有する改変防止(tamper−resistant)剤形
CN105682643B (zh) 2013-07-12 2019-12-13 格吕伦塔尔有限公司 含有乙烯-醋酸乙烯酯聚合物的防篡改剂型
WO2015023675A2 (en) 2013-08-12 2015-02-19 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
WO2015071380A1 (en) 2013-11-13 2015-05-21 Euro-Celtique S.A. Hydromorphone and naloxone for treatment of pain and opioid bowel dysfunction syndrome
AU2014356581C1 (en) 2013-11-26 2020-05-28 Grunenthal Gmbh Preparation of a powdery pharmaceutical composition by means of cryo-milling
US9456986B2 (en) 2013-12-11 2016-10-04 Develco Pharma Schweiz Ag Naloxone mono preparation and multilayer tablet
US10105360B2 (en) 2013-12-11 2018-10-23 Develco Pharma Schweiz Ag Method and composition for the treatment of opioid induced constipation
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
JP2017501228A (ja) * 2013-12-23 2017-01-12 パーデュー、ファーマ、リミテッド、パートナーシップ オピオイド拮抗薬製剤
CA2847781C (en) * 2014-03-28 2019-03-12 Purdue Pharma Reducing drug liking in a subject
EP3142646A1 (en) 2014-05-12 2017-03-22 Grünenthal GmbH Tamper resistant immediate release capsule formulation comprising tapentadol
US9872835B2 (en) 2014-05-26 2018-01-23 Grünenthal GmbH Multiparticles safeguarded against ethanolic dose-dumping
AU2015290098B2 (en) 2014-07-17 2018-11-01 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
WO2016064873A1 (en) 2014-10-20 2016-04-28 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form
WO2016091805A2 (de) * 2014-12-08 2016-06-16 Develco Pharma Schweiz Ag Naloxon-monopräparat und mehrschichttablette
US20160310437A1 (en) 2015-04-24 2016-10-27 Grünenthal GmbH Tamper-resistant fixed dose combination providing fast release of two drugs from particles
CN107889459A (zh) 2015-04-24 2018-04-06 格吕伦塔尔有限公司 具有立即释放和对溶剂萃取的抗性的抗篡改剂型
MX2017013643A (es) 2015-04-24 2018-03-08 Gruenenthal Gmbh Combinacion de dosis fija resistente a la manipulacion que proporciona una liberacion rapida de dos farmacos desde particulas y una matriz.
BR112017022846A2 (pt) 2015-04-24 2018-07-17 Gruenenthal Gmbh combinação de dose fixa inviolável que proporciona rápida liberação de dois fármacos de partículas diferentes
EP3346991A1 (en) 2015-09-10 2018-07-18 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
US9943513B1 (en) 2015-10-07 2018-04-17 Banner Life Sciences Llc Opioid abuse deterrent dosage forms
US10335405B1 (en) 2016-05-04 2019-07-02 Patheon Softgels, Inc. Non-burst releasing pharmaceutical composition
EP3290027A1 (en) * 2016-09-02 2018-03-07 Develco Pharma Schweiz AG Method and composition for the treatment of opioid induced constipation
US10335375B2 (en) 2017-05-30 2019-07-02 Patheon Softgels, Inc. Anti-overingestion abuse deterrent compositions
EP3473246A1 (en) 2017-10-19 2019-04-24 Capsugel Belgium NV Immediate release abuse deterrent formulations

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19710008A1 (de) * 1997-03-12 1998-09-17 Basf Ag Feste, mindestens zweiphasige Zubereitungsformen eines Opioid-Analgeticums mit verzögerter Freisetzung
WO2003007802A2 (en) * 2001-07-18 2003-01-30 Euro-Celtique, S.A. Pharmaceutical combinations of oxycodone and naloxone
US7141250B2 (en) 2001-08-06 2006-11-28 Euro-Celtique S.A. Pharmaceutical formulation containing bittering agent
AU2002321879A1 (en) 2001-08-06 2003-03-03 Thomas Gruber Pharmaceutical formulation containing dye
DE20308437U1 (de) 2002-04-05 2003-11-13 Euroceltique S.A., Luxemburg/Luxembourg Matrix zur verzögerten, gleichbleibenden und unabhängigen Freisetzung von Wirkstoffen
DE10336400A1 (de) 2003-08-06 2005-03-24 Grünenthal GmbH Gegen Missbrauch gesicherte Darreichungsform
DE10361596A1 (de) 2003-12-24 2005-09-29 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
PT1842533E (pt) * 2003-08-06 2013-05-17 Gruenenthal Gmbh Forma de dosagem protegida contra abuso
DE102005005446A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Bruchfeste Darreichungsformen mit retardierter Freisetzung
JP5064209B2 (ja) 2004-04-22 2012-10-31 グリューネンタール・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 乱用防止固体剤形を製造する方法
CA2572352A1 (en) 2004-07-01 2006-01-12 Gruenenthal Gmbh Oral dosage form safeguarded against abuse containing (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol
WO2006002884A1 (de) 2004-07-01 2006-01-12 Grünenthal GmbH Gegen missbrauch gesicherte, orale darreichtungsform
EP1765298B1 (de) 2004-07-01 2012-10-24 Gruenenthal Gmbh Verfahren zur herstellung einer gegen missbrauch gesicherten, festen darreichungsform unter verwendung eines planetwalzenextruders
DE602005007237D1 (de) * 2004-07-27 2008-07-10 Unilever Nv Haarpflegezusammensetzungen
DE102005005449A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
US20060194759A1 (en) * 2005-02-25 2006-08-31 Eidelson Stewart G Topical compositions and methods for treating pain and inflammation
JP2009523833A (ja) * 2006-01-21 2009-06-25 アボット ゲーエムベーハー ウント カンパニー カーゲー 乱用薬剤送達のための製剤および方法
DE102007011485A1 (de) 2007-03-07 2008-09-11 Grünenthal GmbH Darreichungsform mit erschwertem Missbrauch
AU2009277239B2 (en) 2008-07-31 2015-08-06 Nidera Seeds Holding B.V. Herbicide resistant sunflower plants
GB0909680D0 (en) * 2009-06-05 2009-07-22 Euro Celtique Sa Dosage form
ES2560210T3 (es) * 2009-07-22 2016-02-17 Grünenthal GmbH Forma de dosificación resistente a la manipulación para opiádes sensibles a la oxidación

Also Published As

Publication number Publication date
AU2012320496B2 (en) 2017-05-18
CO6950467A2 (es) 2014-05-20
BR112014008120A2 (pt) 2017-04-11
WO2013050539A3 (en) 2013-05-30
AU2012320496C1 (en) 2017-09-28
EA029508B1 (ru) 2018-04-30
EP2763664A2 (en) 2014-08-13
CN103998025A (zh) 2014-08-20
IL230819A0 (en) 2014-03-31
ECSP14013269A (es) 2014-12-30
MX2014003973A (es) 2014-05-07
NZ620252A (en) 2015-09-25
AR088250A1 (es) 2014-05-21
HK1200741A1 (en) 2015-08-14
PE20141171A1 (es) 2014-09-21
US20130090349A1 (en) 2013-04-11
JP2014528437A (ja) 2014-10-27
AU2012320496A1 (en) 2014-02-13
EA201400413A1 (ru) 2014-11-28
KR20140075704A (ko) 2014-06-19
CA2850853A1 (en) 2013-04-11
WO2013050539A2 (en) 2013-04-11

Similar Documents

Publication Publication Date Title
CL2014000361A1 (es) Forma de dosificacion farmaceutica oral resistente a rompimiento de al menos 300n comprendiendo agonista opioide, antagonista opioide y un oxido de polialquileno de pm 200.000 g/mol
CL2014000904A1 (es) Forma de dosis farmaceutica oral resistente a la ruptura que comprende i) un ingrediente farmacologicamente activo, ii) un antagonista opioide y/o un agente repelente, iii) un oxido de polialquileno y iv) un polimero anionico.
FIC20200022I1 (fi) Yhdistelmä, joka käsittää fosnetupitanttia tai sen farmaseuttisesti hyväksyttävää suolaa ja palonosetronia tai sen farmaseuttisesti hyväksyttävää suolaa
NL301197I2 (nl) daridorexant of een farmaceutisch aanvaardbaar zout daarvan, in het bijzonder daridorexanthydrochloride
IL227770A0 (en) Preparations containing an opioid agonist and a separated antagonist
SI2588090T1 (sl) Trdne peroralne farmacevtske oblike, ki obsegajo dabigatran eteksilat in njegove farmacevtsko sprejemljive soli
CL2013001943A1 (es) Uso de un agonista opioide y un antagonista opioide para preparar una forma farmaceutica para el tratamiento de la enfermedad de parkinson y/o al menos un sintoma de la misma.
BRPI0906467A2 (pt) forma de dose farmacêutica
HK1189510A1 (zh) 抗篡改固體口服劑型
IL228506A (en) Opioid receptor ligands and pharmacy preparations containing them
DK2706982T4 (da) Intranasale farmaceutiske dosisformer omfattende naloxon
CO6852076A2 (es) Composiciones farmacéuticas inhalables
BRPI0821683A2 (pt) Medicamento compreendendo um agonista parassimpatético e um antagonista simpatético ou agonista simpatético
IL231485A (en) Oral dosage forms of medicinal preparations are resistant to abuse
IT1398930B1 (it) Formulazioni farmaceutiche bistrato contenenti agonisti ed antagonisti oppioidi.
BRPI1011453A2 (pt) formulacao, forma de dosagem de um medicamento, e, sal de hemipamoato de asenapina
CL2014000844A1 (es) Formulacion farmaceutica oral de liberacion prolongada en forma de multiparticulas, que comprende a) 40-o-(2-hidroxi)etil-rapamicina y b) al menos un recubrimiento de liberacion prolongada.
BRPI0812964A2 (pt) Forma de dosagem farmacêutica oral sólida
SMT201500005B (it) Composizione framaceutica inalabile
HUE038543T2 (hu) MGBG-t tartalmazó szabályozott kibocsátású orális gyógyszerészeti dózis-formák
BR112012015016A2 (pt) formulação farmacèutica e forma de dosagem farmacêutica entérica
EP2781512A4 (en) OXADIAZOLE COMPOUND AND PROCESS FOR PREPARING THE SAME, PHARMACEUTICAL COMPOSITION AND USE THEREOF
DK2396006T3 (da) Doramectinformulering med høj dosis
BR112013019283A2 (pt) composto, fármaco, composição farmacêutica e uso
DK2714042T3 (da) En analgetisk farmaceutisk sammensætning til oral administration