CA2753664C - Abuse resistant formulation - Google Patents
Abuse resistant formulation Download PDFInfo
- Publication number
- CA2753664C CA2753664C CA2753664A CA2753664A CA2753664C CA 2753664 C CA2753664 C CA 2753664C CA 2753664 A CA2753664 A CA 2753664A CA 2753664 A CA2753664 A CA 2753664A CA 2753664 C CA2753664 C CA 2753664C
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- CA
- Canada
- Prior art keywords
- composition
- excipient
- active ingredient
- forming agent
- film
- 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.)
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- 239000000203 mixture Substances 0.000 title claims abstract description 111
- 238000009472 formulation Methods 0.000 title abstract description 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 79
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 52
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 43
- 239000000014 opioid analgesic Substances 0.000 claims abstract description 28
- 208000002193 Pain Diseases 0.000 claims abstract description 22
- 239000011148 porous material Substances 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 238000013268 sustained release Methods 0.000 claims abstract description 12
- 239000012730 sustained-release form Substances 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
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- 238000000034 method Methods 0.000 claims description 32
- 229910000323 aluminium silicate Inorganic materials 0.000 claims description 30
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- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 claims description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 3
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- YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 claims description 2
- LGFMXOTUSSVQJV-NEYUFSEYSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;(4r,4ar,7s,7ar,12bs)-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol;1-[(3,4-dimethoxyphenyl)methyl]-6 Chemical compound Cl.Cl.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 LGFMXOTUSSVQJV-NEYUFSEYSA-N 0.000 claims description 2
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Classifications
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A—HUMAN NECESSITIES
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Inorganic Chemistry (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (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)
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| PCT/GB2010/000374 WO2010100414A1 (en) | 2009-03-04 | 2010-03-02 | Abuse resistant formulation |
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| CA2753664A1 CA2753664A1 (en) | 2010-09-10 |
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| EP2445487A2 (en) | 2009-06-24 | 2012-05-02 | Egalet Ltd. | Controlled release formulations |
| SG174465A1 (en) | 2009-10-30 | 2011-10-28 | Ix Biopharma Pte Ltd | Fast dissolving solid dosage form |
| US12186426B2 (en) | 2009-10-30 | 2025-01-07 | Ix Biopharma Ltd. | Solid dosage form |
| MX392839B (es) * | 2012-11-30 | 2025-03-24 | Acura Pharmaceuticals Inc | Liberacion autorregulada de ingrediente farmaceutico activo. |
| US10420729B2 (en) | 2013-03-15 | 2019-09-24 | R.P. Scherer Technologies, Llc | Abuse resistant capsule |
| WO2015023675A2 (en) | 2013-08-12 | 2015-02-19 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded immediate release abuse deterrent pill |
| US10172797B2 (en) | 2013-12-17 | 2019-01-08 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| AU2015290098B2 (en) | 2014-07-17 | 2018-11-01 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
| AU2015336065A1 (en) | 2014-10-20 | 2017-05-04 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
| CA2902911C (en) | 2014-10-31 | 2017-06-27 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
| GB201502073D0 (en) | 2015-02-09 | 2015-03-25 | Cubic Pharmaceuticals Ltd And Delta Pharmaceuticals Ltd | HDEG technology |
| US10398343B2 (en) | 2015-03-02 | 2019-09-03 | Mc10, Inc. | Perspiration sensor |
| EP3210596A1 (en) * | 2016-02-29 | 2017-08-30 | G.L. Pharma GmbH | Abuse-deterrent pharmaceutical composition |
| WO2017149287A1 (en) * | 2016-02-29 | 2017-09-08 | Emplicure Ab | Devices for evaporation and inhalation of active agents |
| CN105769798A (zh) * | 2016-05-16 | 2016-07-20 | 张阳 | 一种高血压治疗药物的制备方法 |
| CN105997915A (zh) * | 2016-05-16 | 2016-10-12 | 张阳 | 一种高血压治疗用缓释片剂 |
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| AUPQ573300A0 (en) | 2000-02-21 | 2000-03-16 | Australian Nuclear Science & Technology Organisation | Controlled release ceramic particles, compositions thereof, processes of preparation and methods of use |
| US7011841B2 (en) | 2000-03-24 | 2006-03-14 | Mark B. Lyles | High density porous materials |
| BR0109991A (pt) | 2000-04-11 | 2003-05-27 | Sankyo Co | Composição farmacêutica |
| US20020122828A1 (en) | 2001-03-02 | 2002-09-05 | Jun Liu | Hybrid porous materials for controlled release |
| DE60226012T2 (de) * | 2001-03-05 | 2009-05-14 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Geschmacksmaskierte pharmazeutische formulierungen |
| EP1429819B1 (en) | 2001-09-24 | 2010-11-24 | Boston Scientific Limited | Optimized dosing for paclitaxel coated stents |
| PT1429802E (pt) | 2001-09-28 | 2013-01-24 | Tntgamble Inc | Sistema de entrega para componente biológico |
| CA2467559A1 (en) | 2001-11-19 | 2003-05-30 | Control Delivery Systems, Inc. | Topical delivery of codrugs |
| MXPA04010612A (es) | 2002-04-23 | 2005-07-14 | Alza Corp | Sistemas analgesicos transdermicos con potencial reducido de abuso. |
| AU2003222691A1 (en) | 2002-04-30 | 2003-11-17 | Morteza Shirkhanzadeh | Arrays of microneedles comprising porous calcium phosphate coating and bioactive agents |
| AU2003275311A1 (en) | 2002-09-16 | 2004-04-30 | Sung-Yun Kwon | Solid micro-perforators and methods of use |
| SE524334C2 (sv) | 2002-09-30 | 2004-07-27 | Cerbio Tech Ab | Värmegenererande biokompatibla keramiska material och förfarande för dess framställning |
| SE525236C2 (sv) | 2002-10-31 | 2005-01-11 | Cerbio Tech Ab | Förfarande för framställning av strukturerade keramiska beläggningar och belagda anordningar framställda med detta förfarande |
| SE524494C2 (sv) | 2002-12-31 | 2004-08-17 | Doxa Ab | Kemiskt bundna biomaterialelement med skräddarsydda egenskaper |
| WO2005037268A1 (ja) | 2003-10-15 | 2005-04-28 | Ltt Bio-Pharma Co., Ltd. | 多価金属無機塩被覆レチノイン酸ナノ粒子含有組成物 |
| KR20060115398A (ko) | 2003-10-29 | 2006-11-08 | 독사 악티에볼락 | 개선된 생체 재료의 초기 및 최종 특성을 위한 2단계시스템 |
| US20050181049A1 (en) | 2003-11-19 | 2005-08-18 | Dong Liang C. | Composition and method for enhancing bioavailability |
| EA010826B1 (ru) | 2003-12-31 | 2008-12-30 | Сайма Лэбс Инк. | Лекарственная форма фентанила для перорального применения, способ ее получения и способы лечения |
| WO2005075016A1 (ja) | 2004-02-03 | 2005-08-18 | Hisamitsu Pharmaceutical Co., Inc. | 経皮薬物投与装置用インタフェース |
| US7315758B2 (en) | 2004-06-03 | 2008-01-01 | Lynntech, Inc. | Transdermal delivery of therapeutic agent |
| US20060016578A1 (en) * | 2004-06-24 | 2006-01-26 | Shine Ying Co., Ltd. | [high-performance two-phase flow evaporator] |
| CN101001613B (zh) | 2004-06-28 | 2010-09-29 | 生命周期药物公司 | 作为液体制剂载体的多孔片剂 |
| US20060127486A1 (en) | 2004-07-13 | 2006-06-15 | Moerck Rudi E | Ceramic structures for prevention of drug diversion |
| AU2005271782A1 (en) * | 2004-07-13 | 2006-02-16 | Altairnano, Inc. | Ceramic structures for controlled release of drugs |
| US7537590B2 (en) | 2004-07-30 | 2009-05-26 | Microchips, Inc. | Multi-reservoir device for transdermal drug delivery and sensing |
| CA2577583A1 (en) | 2004-08-19 | 2006-03-02 | Alza Corporation | Controlled release nanoparticle active agent formulation dosage forms and methods |
| US8535702B2 (en) | 2005-02-01 | 2013-09-17 | Boston Scientific Scimed, Inc. | Medical devices having porous polymeric regions for controlled drug delivery and regulated biocompatibility |
| FR2881652B1 (fr) | 2005-02-08 | 2007-05-25 | Flamel Technologies Sa | Forme pharmaceutique orale microparticulaire anti-mesuage |
| WO2006096544A1 (en) | 2005-03-04 | 2006-09-14 | Altairnano, Inc. | Ceramic structures for controlled release of biologically active substances |
| DE102005040429A1 (de) | 2005-08-25 | 2007-03-01 | Heraeus Kulzer Gmbh | Wirkstofffreisetzungssystem und seine Verwendung |
| US8652529B2 (en) | 2005-11-10 | 2014-02-18 | Flamel Technologies | Anti-misuse microparticulate oral pharmaceutical form |
| US7682445B2 (en) | 2005-12-08 | 2010-03-23 | Doxa Ab | Powdered CBC system with improved reaction feature |
| WO2007074349A2 (en) | 2005-12-29 | 2007-07-05 | Robert Basic | Mineral-herbal preparation consisting of zeolite and astragalus membranaceus root extract to treat allergies |
| US20070212414A1 (en) | 2006-03-08 | 2007-09-13 | Penwest Pharmaceuticals Co. | Ethanol-resistant sustained release formulations |
| US20070248656A1 (en) | 2006-04-25 | 2007-10-25 | Galer Bradley S | Topical preparation dispensers and methods of using the same |
| US9023400B2 (en) | 2006-05-24 | 2015-05-05 | Flamel Technologies | Prolonged-release multimicroparticulate oral pharmaceutical form |
| DE102006028781A1 (de) | 2006-06-23 | 2007-12-27 | Robert Bosch Gmbh | Verfahren zur Herstellung von porösen Mikronadeln und ihre Verwendung |
| US20080214987A1 (en) | 2006-12-22 | 2008-09-04 | Nanomed Devices, Inc. | Microdevice And Method For Transdermal Delivery And Sampling Of Active Substances |
| WO2008105737A1 (en) | 2007-03-01 | 2008-09-04 | Doxa Ab | Stable cement composition for orthopaedic and dental use |
| US8778377B2 (en) | 2007-03-01 | 2014-07-15 | Doxa Ab | Drug implant carrier for drug delivery |
| WO2008105738A1 (en) | 2007-03-01 | 2008-09-04 | Doxa Ab | Injectable cement composition for orthopaedic and dental use |
| WO2008118096A1 (en) | 2007-03-28 | 2008-10-02 | Doxa Ab | Carriers for drug delivery |
| CN101104080B (zh) | 2007-04-24 | 2011-06-22 | 深圳市鸿华投资有限公司 | 沸石止血敷料及其制备方法和用途 |
| GB0709541D0 (en) | 2007-05-17 | 2007-06-27 | Jagotec Ag | Pharmaceutical excipient |
| EP2100850A1 (en) | 2008-03-11 | 2009-09-16 | Stichting Voor De Technische Wetenschappen | Microneedle array and a method for manufacturing microneedles |
| EP2398577A2 (en) | 2009-02-19 | 2011-12-28 | Bonner, Alex Garfield | Porous interpenetrating polymer network |
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2010
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- 2010-03-02 MX MX2011009214A patent/MX336355B/es unknown
- 2010-03-02 WO PCT/GB2010/000374 patent/WO2010100414A1/en not_active Ceased
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- 2010-03-02 BR BRPI1009121A patent/BRPI1009121A2/pt not_active Application Discontinuation
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- 2010-03-02 EA EA201101281A patent/EA031154B1/ru not_active IP Right Cessation
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Also Published As
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|---|---|
| AU2010219449A1 (en) | 2011-09-01 |
| US9622972B2 (en) | 2017-04-18 |
| AU2010219449B2 (en) | 2014-12-18 |
| NO2403482T3 (enExample) | 2018-05-26 |
| US20170239229A1 (en) | 2017-08-24 |
| MX2011009214A (es) | 2011-09-28 |
| IL214583A (en) | 2016-04-21 |
| ES2660674T3 (es) | 2018-03-23 |
| IL214583A0 (en) | 2011-09-27 |
| JP2012519675A (ja) | 2012-08-30 |
| BRPI1009121A2 (pt) | 2018-06-19 |
| PL2403482T3 (pl) | 2018-06-29 |
| CN102341096B (zh) | 2015-02-18 |
| US10543203B2 (en) | 2020-01-28 |
| EP2403482A1 (en) | 2012-01-11 |
| US20120015007A1 (en) | 2012-01-19 |
| CN102341096A (zh) | 2012-02-01 |
| MX336355B (es) | 2016-01-14 |
| KR20110122838A (ko) | 2011-11-11 |
| WO2010100414A1 (en) | 2010-09-10 |
| KR101751906B1 (ko) | 2017-06-29 |
| EA201101281A1 (ru) | 2012-02-28 |
| CA2753664A1 (en) | 2010-09-10 |
| DK2403482T3 (en) | 2018-03-05 |
| NZ594513A (en) | 2013-10-25 |
| EP2403482B1 (en) | 2017-12-27 |
| JP5728705B2 (ja) | 2015-06-03 |
| EA031154B1 (ru) | 2018-11-30 |
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