DE69531216D1 - Verabreichungssystem mit gesteuerter freisetzung einer arzneistoffsuspension - Google Patents

Verabreichungssystem mit gesteuerter freisetzung einer arzneistoffsuspension

Info

Publication number
DE69531216D1
DE69531216D1 DE69531216T DE69531216T DE69531216D1 DE 69531216 D1 DE69531216 D1 DE 69531216D1 DE 69531216 T DE69531216 T DE 69531216T DE 69531216 T DE69531216 T DE 69531216T DE 69531216 D1 DE69531216 D1 DE 69531216D1
Authority
DE
Germany
Prior art keywords
controlled release
administration system
drug suspension
hydration
gel beads
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
DE69531216T
Other languages
English (en)
Other versions
DE69531216T2 (de
Inventor
Gerald S Rork
James D Pipkin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
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 Merck and Co Inc filed Critical Merck and Co Inc
Application granted granted Critical
Publication of DE69531216D1 publication Critical patent/DE69531216D1/de
Publication of DE69531216T2 publication Critical patent/DE69531216T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • 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
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
DE69531216T 1994-12-22 1995-12-18 Verabreichungssystem mit gesteuerter freisetzung einer arzneistoffsuspension Expired - Fee Related DE69531216T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/363,451 US5582838A (en) 1994-12-22 1994-12-22 Controlled release drug suspension delivery device
PCT/US1995/016530 WO1996019201A1 (en) 1994-12-22 1995-12-18 A controlled release drug suspension delivery device
US363451 1999-07-29

Publications (2)

Publication Number Publication Date
DE69531216D1 true DE69531216D1 (de) 2003-08-07
DE69531216T2 DE69531216T2 (de) 2004-05-27

Family

ID=23430259

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69531216T Expired - Fee Related DE69531216T2 (de) 1994-12-22 1995-12-18 Verabreichungssystem mit gesteuerter freisetzung einer arzneistoffsuspension

Country Status (20)

Country Link
US (1) US5582838A (de)
EP (1) EP0801560B1 (de)
JP (1) JPH11509829A (de)
CN (1) CN1081916C (de)
AT (1) ATE244001T1 (de)
AU (1) AU693313B2 (de)
CZ (1) CZ290802B6 (de)
DE (1) DE69531216T2 (de)
DK (1) DK0801560T3 (de)
ES (1) ES2201133T3 (de)
FI (1) FI972586A (de)
HU (1) HUT77370A (de)
MX (1) MX9704672A (de)
NO (1) NO320641B1 (de)
NZ (1) NZ298994A (de)
PL (1) PL183615B1 (de)
PT (1) PT801560E (de)
RU (1) RU2168330C2 (de)
SK (1) SK281224B6 (de)
WO (1) WO1996019201A1 (de)

Families Citing this family (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3016251A1 (de) * 1980-04-26 1981-11-05 Linde Ag, 6200 Wiesbaden Verfahren zur regelung einer absorptions-heizanlage
US6239172B1 (en) * 1997-04-10 2001-05-29 Nitrosystems, Inc. Formulations for treating disease and methods of using same
US20110196039A9 (en) * 1994-10-05 2011-08-11 Kaesemeyer Wayne H Controlled release arginine formulations
US5914134A (en) * 1997-01-27 1999-06-22 Wockhardt Europe Limited Process for the pulsatile delivery of diltiazem HCL and product produced thereby
US5837379A (en) * 1997-01-31 1998-11-17 Andrx Pharmaceuticals, Inc. Once daily pharmaceutical tablet having a unitary core
US5922352A (en) * 1997-01-31 1999-07-13 Andrx Pharmaceuticals, Inc. Once daily calcium channel blocker tablet having a delayed release core
US6110499A (en) * 1997-07-24 2000-08-29 Alza Corporation Phenytoin therapy
PT1017390E (pt) * 1997-07-31 2007-07-24 Kos Life Sciences Inc Comprimido revestido que compreende ácido nicotínico ou um composto metabolizado a ácido nicotínico sob uma forma de libertação prolongada, e um revestimento que contém um inibidor da hmg-coa-redutase sob uma forma de libertação imediata.
US5989463A (en) * 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
US8679534B2 (en) * 1997-12-12 2014-03-25 Andrx Labs, Llc HMG-CoA reductase inhibitor extended release formulation
US6485748B1 (en) 1997-12-12 2002-11-26 Andrx Pharmaceuticals, Inc. Once daily pharmaceutical tablet having a unitary core
US20040029962A1 (en) * 1997-12-12 2004-02-12 Chih-Ming Chen HMG-COA reductase inhibitor extended release formulation
US5916595A (en) * 1997-12-12 1999-06-29 Andrx Pharmaceutials, Inc. HMG co-reductase inhibitor
FR2774910B1 (fr) * 1998-02-16 2001-09-07 Ethypharm Lab Prod Ethiques Microgranules de sulfate de morphine, procede de fabrication et preparations pharmaceutiques
US6110500A (en) * 1998-03-25 2000-08-29 Temple University Coated tablet with long term parabolic and zero-order release kinetics
KR100827254B1 (ko) 1998-06-03 2008-05-07 알자 코포레이션 연장된 약물 치료를 제공하기 위한 방법 및 장치
AU4013900A (en) * 1999-03-19 2000-10-09 Enos Pharmaceuticals, Inc. Increasing cerebral bioavailability of drugs
US6211246B1 (en) * 1999-06-10 2001-04-03 Mcneil-Ppc, Inc. Rapidly absorbed liquid compositions
US7235258B1 (en) * 1999-10-19 2007-06-26 Nps Pharmaceuticals, Inc. Sustained-release formulations for treating CNS-mediated disorders
US20020107173A1 (en) * 1999-11-04 2002-08-08 Lawrence Friedhoff Method of treating amyloid beta precursor disorders
EP1225880A2 (de) * 1999-11-04 2002-07-31 Andrx Corporation Verwendung von einem hgm coa-reduktase inhibitor zur behandlung von amyloid-beta-precursor störungen
GB2371748B (en) * 1999-11-08 2004-12-01 Andrx Corp HMG-COA reductase inhibitor extended release formulation
ES2401598T3 (es) * 2000-04-10 2013-04-22 Teva Pharmaceutical Industries, Ltd. Composiciones farmacéuticas estables que contienen ácidos 7-sustituido-3,5-dihidroxiheptanoicos o ácidos 7-sustituido-3,5-dihidroxiheptenoicos
USRE44578E1 (en) 2000-04-10 2013-11-05 Teva Pharmaceutical Industries, Ltd. Stable pharmaceutical compositions containing 7-substituted-3,5-dihydroxyheptanoic acids or 7-substituted-3,5-dihydroxyheptenoic acids
US6635277B2 (en) 2000-04-12 2003-10-21 Wockhardt Limited Composition for pulsatile delivery of diltiazem and process of manufacture
US6242003B1 (en) 2000-04-13 2001-06-05 Novartis Ag Organic compounds
WO2001080796A1 (en) * 2000-04-26 2001-11-01 Watson Pharmaceuticals, Inc. Minimizing adverse experience associated with oxybutynin therapy
US7179483B2 (en) * 2000-04-26 2007-02-20 Watson Pharmaceuticals, Inc. Compositions and methods for transdermal oxybutynin therapy
US7029694B2 (en) * 2000-04-26 2006-04-18 Watson Laboratories, Inc. Compositions and methods for transdermal oxybutynin therapy
US6419954B1 (en) * 2000-05-19 2002-07-16 Yamanouchi Pharmaceutical Co., Ltd. Tablets and methods for modified release of hydrophilic and other active agents
NZ524348A (en) * 2000-08-02 2004-07-30 Malope Company Ltd Diagnosis and treatment of non-ulcer dyspepsia based on dysfunction in the corticotropin releasing hormone (CRH) receptor and repsonse to ACTH
US6296842B1 (en) 2000-08-10 2001-10-02 Alkermes Controlled Therapeutics, Inc. Process for the preparation of polymer-based sustained release compositions
US6479065B2 (en) 2000-08-10 2002-11-12 Alkermes Controlled Therapeutics, Inc. Process for the preparation of polymer-based sustained release compositions
AU2141202A (en) * 2000-12-05 2002-06-18 Alexander Macgregor Hydrostatic delivery system for controlled delivery of agent
US20060127474A1 (en) 2001-04-11 2006-06-15 Oskar Kalb Pharmaceutical compositions comprising fluvastatin
JP4993652B2 (ja) * 2004-03-31 2012-08-08 リンテック株式会社 経口投与剤
US8268333B2 (en) * 2001-04-24 2012-09-18 Lintec Corporation Orally administered agent and an orally administered agent/supporting substrate complex
US20080058424A1 (en) * 2002-05-23 2008-03-06 Cephalon, Inc. Novel pharmaceutical formulations of modafinil
GB0117618D0 (en) * 2001-07-19 2001-09-12 Phoqus Ltd Pharmaceutical dosage form
US20040253312A1 (en) * 2001-09-28 2004-12-16 Sowden Harry S. Immediate release dosage form comprising shell having openings therein
CN100408029C (zh) * 2001-09-28 2008-08-06 麦克内尔-Ppc股份有限公司 有镶嵌部分的组合剂型
US20040052843A1 (en) * 2001-12-24 2004-03-18 Lerner E. Itzhak Controlled release dosage forms
BR0215413A (pt) * 2001-12-24 2004-12-14 Teva Pharma Formula dosada com um comprimido central de ingrediente ativo encapado em uma capa anular prensada de material em pó ou granulado e processo e conjunto de ferramentas para a sua produção
EP1478349A1 (de) * 2002-02-21 2004-11-24 Amarin Development AB Methode zur freisetzung von nanopartikeln eines wirkstoffes aus einer diffusions-kontrollierten pharmazeutischen zubereitung zur oralen anwendung
EA005866B1 (ru) * 2002-03-04 2005-06-30 Тева Фармасьютикал Индастриес Лтд. Лекарственная форма с регулируемым высвобождением активного ингредиента
CA2478772C (en) * 2002-03-11 2011-01-18 Alcon, Inc. Implantable drug delivery system
CA2379887C (en) * 2002-04-09 2004-01-20 Bernard Charles Sherman Stable tablets comprising simvastatin
AU2003220468A1 (en) * 2002-09-28 2004-04-19 Mcneil-Ppc, Inc. Solid dosage form comprising ketoprofen
US20040219210A1 (en) * 2003-05-01 2004-11-04 Jian-Hwa Guo Controlled release solid dosage nifedipine formulations
CA2536401C (en) * 2003-11-04 2011-08-30 Shire Laboratories Inc. Compositions of quaternary ammonium compounds containing bioavailability enhancers
ATE493981T1 (de) 2003-11-04 2011-01-15 Supernus Pharmaceuticals Inc Einmal tägliche dosierformen von trospium
US7387793B2 (en) 2003-11-14 2008-06-17 Eurand, Inc. Modified release dosage forms of skeletal muscle relaxants
US8734850B2 (en) 2003-11-25 2014-05-27 Flamel Technologies Oral medicinal product with modified release of at least one active principle in multimicrocapsular form
US7879354B2 (en) * 2004-01-13 2011-02-01 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US8067029B2 (en) * 2004-01-13 2011-11-29 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
JP2005298471A (ja) * 2004-03-17 2005-10-27 Lintec Corp 薬剤の製造方法
JP2005289867A (ja) * 2004-03-31 2005-10-20 Lintec Corp 経口投与剤
KR100598326B1 (ko) * 2004-04-10 2006-07-10 한미약품 주식회사 HMG-CoA 환원효소 억제제의 경구투여용 서방형 제제및 이의 제조방법
KR101340946B1 (ko) * 2004-08-04 2013-12-13 알자 코포레이션 오름차 0차 방출 패턴을 나타내는 약물의 서방성 조성물,상기 조성물을 제조하는 방법
US8778395B2 (en) * 2005-08-11 2014-07-15 Andrx Labs, Llc Diltiazem controlled release formulation and method of manufacture
WO2008006083A2 (en) 2006-07-07 2008-01-10 Surmodics, Inc. Beaded wound spacer device
US7731604B2 (en) * 2006-10-31 2010-06-08 Taylor Made Golf Company, Inc. Golf club iron head
WO2009122431A2 (en) * 2008-02-15 2009-10-08 Sun Pharma Advanced Research Company Ltd., Oral controlled release tablet
US20100144800A1 (en) * 2008-06-11 2010-06-10 Ranbaxy Laboratories Limited extended release tablet formulation of niacin
FR2940116B1 (fr) * 2008-12-22 2012-07-06 Philippe Perovitch Formulation pour l'administration d'hypolipemiant par voie trans-muqueuse buccale
WO2012042314A1 (en) 2010-10-02 2012-04-05 Link Research & Grants Corporation Treatment of tinnitus and related auditory dysfunctions
DE102011051653A1 (de) * 2011-07-07 2013-01-10 Lts Lohmann Therapie-Systeme Ag Quellfähige Manteltablette
CA2888241C (en) 2012-10-16 2020-12-29 Surmodics, Inc. Wound packing device and methods
WO2015150948A1 (en) 2014-03-29 2015-10-08 Wockhardt Limited Modified release solid oral pharmaceutical compositions of cyclobenzaprine or a salt thereof
CN103948557A (zh) * 2014-04-08 2014-07-30 闻晓光 一种新型控释片
US10201457B2 (en) 2014-08-01 2019-02-12 Surmodics, Inc. Wound packing device with nanotextured surface
WO2016209779A1 (en) * 2015-06-22 2016-12-29 Schlumberger Technology Corporation Hydratable polymer slurry and methods for making and using same

Family Cites Families (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB972128A (en) * 1960-01-21 1964-10-07 Wellcome Found Pellets for supplying biologically active substances to ruminants and the manufacture of such pellets
US3538214A (en) * 1969-04-22 1970-11-03 Merck & Co Inc Controlled release medicinal tablets
US3845770A (en) * 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
GB1456365A (en) * 1972-10-06 1976-11-24 Gist Brocades Nv Controlled release composition
JPS5518694B2 (de) * 1973-04-02 1980-05-21
US3916899A (en) * 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4218433A (en) * 1977-03-03 1980-08-19 Nippon Kayaku Kabushiki Kaisha Constant-rate eluting tablet and method of producing same
US4256108A (en) * 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
US4160452A (en) * 1977-04-07 1979-07-10 Alza Corporation Osmotic system having laminated wall comprising semipermeable lamina and microporous lamina
US4220153A (en) * 1978-05-08 1980-09-02 Pfizer Inc. Controlled release delivery system
US4285987A (en) * 1978-10-23 1981-08-25 Alza Corporation Process for manufacturing device with dispersion zone
US4200098A (en) * 1978-10-23 1980-04-29 Alza Corporation Osmotic system with distribution zone for dispensing beneficial agent
US4210139A (en) * 1979-01-17 1980-07-01 Alza Corporation Osmotic device with compartment for governing concentration of agent dispensed from device
US4235236A (en) * 1979-02-12 1980-11-25 Alza Corporation Device for dispensing drug by combined diffusional and osmotic operations
DE3067332D1 (en) * 1979-06-27 1984-05-10 Beecham Group Plc Veterinary preparations for ruminant animals
US4309996A (en) * 1980-04-28 1982-01-12 Alza Corporation System with microporous releasing diffusor
US4326525A (en) * 1980-10-14 1982-04-27 Alza Corporation Osmotic device that improves delivery properties of agent in situ
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4455143A (en) * 1982-03-22 1984-06-19 Alza Corporation Osmotic device for dispensing two different medications
US4557925A (en) * 1982-07-08 1985-12-10 Ab Ferrosan Membrane-coated sustained-release tablets and method
US5366738A (en) * 1982-07-29 1994-11-22 Merck & Co., Inc. Controlled release drug dispersion delivery device
US4681583A (en) * 1982-12-20 1987-07-21 Alza Corporation System for dispersing drug in biological environment
US4578075A (en) * 1982-12-20 1986-03-25 Alza Corporation Delivery system housing a plurality of delivery devices
US4783337A (en) * 1983-05-11 1988-11-08 Alza Corporation Osmotic system comprising plurality of members for dispensing drug
GB8319766D0 (en) * 1983-07-22 1983-08-24 Graham N B Controlled release device
GB8322007D0 (en) * 1983-08-16 1983-09-21 Wellcome Found Pharmaceutical delivery system
US4601893A (en) * 1984-02-08 1986-07-22 Pfizer Inc. Laminate device for controlled and prolonged release of substances to an ambient environment and method of use
US4968507A (en) * 1984-06-20 1990-11-06 Merck & Co., Inc. Controlled porosity osmotic pump
US4851228A (en) * 1984-06-20 1989-07-25 Merck & Co., Inc. Multiparticulate controlled porosity osmotic
US4743247A (en) * 1984-08-13 1988-05-10 Alza Corporation Process for manufacturing dosage form
US4898733A (en) * 1985-11-04 1990-02-06 International Minerals & Chemical Corp. Layered, compression molded device for the sustained release of a beneficial agent
IT1188212B (it) * 1985-12-20 1988-01-07 Paolo Colombo Sistema per il rilascio a velocita' controllata di sostanze attive
US4971790A (en) * 1986-02-07 1990-11-20 Alza Corporation Dosage form for lessening irritation of mocusa
US4915954A (en) * 1987-09-03 1990-04-10 Alza Corporation Dosage form for delivering a drug at two different rates
US4946686A (en) * 1987-09-24 1990-08-07 Merck & Co., Inc. Solubility modulated drug delivery system
US4994273A (en) * 1987-11-02 1991-02-19 Merck & Co., Inc. Solubility modulated drug delivery device
US4996060A (en) * 1988-03-25 1991-02-26 Alza Corporation Device comprising liner for protecting fluid sensitive medicament
GB8820353D0 (en) * 1988-08-26 1988-09-28 Staniforth J N Controlled release tablet
IL92966A (en) * 1989-01-12 1995-07-31 Pfizer Hydrogel-operated release devices
US5030452A (en) * 1989-01-12 1991-07-09 Pfizer Inc. Dispensing devices powered by lyotropic liquid crystals
US5230895A (en) * 1990-05-01 1993-07-27 Copley Pharmaceutical Inc. Sustained released delivery system for use in the periodontal pocket
US5057321A (en) * 1990-06-13 1991-10-15 Alza Corporation Dosage form comprising drug and maltodextrin
WO1993012765A1 (en) * 1991-12-27 1993-07-08 Merck & Co., Inc. A controlled release drug dispersion delivery device

Also Published As

Publication number Publication date
EP0801560B1 (de) 2003-07-02
FI972586A0 (fi) 1997-06-17
NO320641B1 (no) 2006-01-09
NZ298994A (en) 1998-10-28
ES2201133T3 (es) 2004-03-16
AU4472696A (en) 1996-07-10
EP0801560A1 (de) 1997-10-22
US5582838A (en) 1996-12-10
DE69531216T2 (de) 2004-05-27
CN1171048A (zh) 1998-01-21
DK0801560T3 (da) 2003-10-06
WO1996019201A1 (en) 1996-06-27
ATE244001T1 (de) 2003-07-15
JPH11509829A (ja) 1999-08-31
MX9704672A (es) 1998-02-28
EP0801560A4 (de) 1998-08-19
HUT77370A (hu) 1998-03-30
AU693313B2 (en) 1998-06-25
PT801560E (pt) 2003-10-31
FI972586A (fi) 1997-06-17
RU2168330C2 (ru) 2001-06-10
SK80597A3 (en) 1998-02-04
CZ290802B6 (cs) 2002-10-16
PL183615B1 (pl) 2002-06-28
CZ189597A3 (cs) 1998-02-18
PL320792A1 (en) 1997-10-27
CN1081916C (zh) 2002-04-03
SK281224B6 (sk) 2001-01-18
NO972880D0 (no) 1997-06-20
NO972880L (no) 1997-06-20

Similar Documents

Publication Publication Date Title
DE69531216D1 (de) Verabreichungssystem mit gesteuerter freisetzung einer arzneistoffsuspension
NZ502836A (en) Sustained release drug delivery devices
SE9803871D0 (sv) Therapeutic method and formulation
CA2085871A1 (en) A controlled release drug dispersion delivery device
ATE287260T1 (de) Formulierung mit einer vorgeformten öffnung zur gesteuerten freisetzung
ES2112946T3 (es) Sistemas de matriz multicapa para la liberacion controlada de principios activos.
BR9806174A (pt) Péletes tendo um núcleo revestido com um antifúngico e um polìmero
ATE171617T1 (de) Arzneistoffabgabesysteme mit verzögerter freisetzung
DE3774148D1 (de) Im magen verbleibende granula.
NO931859D0 (no) Blanding for kontrollert frigjoering av en aktiv bestanddel
CA2206211A1 (en) A controlled release drug suspension delivery device
DE59706576D1 (de) Orale zubereitung, enthaltend in einer in wässrigem medium quellbaren matrix wenigstens einen pharmazeutischen wirkstoff
BG104757A (en) Pellets having a core coated with a lipid lowering agent and a polymer
DE59607949D1 (de) Feste arzneimittelform mit polymerem material verteiltem wirkstoff
IT1275267B (it) Forme farmaceutiche a rilascio modificato di canrenoato di potassio costituite da matrici idrofile rivestite

Legal Events

Date Code Title Description
8364 No opposition during term of opposition
8339 Ceased/non-payment of the annual fee