CA2661573A1 - Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic - Google Patents

Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic Download PDF

Info

Publication number
CA2661573A1
CA2661573A1 CA002661573A CA2661573A CA2661573A1 CA 2661573 A1 CA2661573 A1 CA 2661573A1 CA 002661573 A CA002661573 A CA 002661573A CA 2661573 A CA2661573 A CA 2661573A CA 2661573 A1 CA2661573 A1 CA 2661573A1
Authority
CA
Canada
Prior art keywords
extended release
dosage form
tablet
temperature
polyethylene oxide
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.)
Granted
Application number
CA002661573A
Other languages
French (fr)
Other versions
CA2661573C (en
Inventor
Richard Owen Mannion
Edward Patrick O'donnell
William Henry Mckenna
Haiyong Hugh Huang
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.)
Purdue Pharma LP
Original Assignee
Purdue Pharma L.P.
Richard Owen Mannion
Edward Patrick O'donnell
William Henry Mckenna
Haiyong Hugh Huang
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=38754532&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2661573(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Purdue Pharma L.P., Richard Owen Mannion, Edward Patrick O'donnell, William Henry Mckenna, Haiyong Hugh Huang filed Critical Purdue Pharma L.P.
Priority to CA2707204A priority Critical patent/CA2707204C/en
Publication of CA2661573A1 publication Critical patent/CA2661573A1/en
Application granted granted Critical
Publication of CA2661573C publication Critical patent/CA2661573C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, 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
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/005—Coating of tablets or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • 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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, 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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, 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
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting 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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B7/00—Mixing; Kneading
    • B29B7/02—Mixing; Kneading non-continuous, with mechanical mixing or kneading devices, i.e. batch type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B7/00—Mixing; Kneading
    • B29B7/80—Component parts, details or accessories; Auxiliary operations
    • B29B7/88—Adding charges, i.e. additives
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/04—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould using liquids, gas or steam
    • B29C35/045—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould using liquids, gas or steam using gas or flames
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/16—Cooling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C37/00—Component parts, details, accessories or auxiliary operations, not covered by group B29C33/00 or B29C35/00
    • B29C37/0025—Applying surface layers, e.g. coatings, decorative layers, printed layers, to articles during shaping, e.g. in-mould printing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/003—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor characterised by the choice of material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/02—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of definite length, i.e. discrete articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/32—Component parts, details or accessories; Auxiliary operations
    • B29C43/52—Heating or cooling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/009—After-treatment of articles without altering their shape; Apparatus therefor using gases without chemical reaction
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/04—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould using liquids, gas or steam
    • B29C35/045—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould using liquids, gas or steam using gas or flames
    • B29C2035/046—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould using liquids, gas or steam using gas or flames dried air
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/16—Cooling
    • B29C2035/1658—Cooling using gas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2071/00—Use of polyethers, e.g. PEEK, i.e. polyether-etherketone or PEK, i.e. polyetherketone or derivatives thereof, as moulding material
    • B29K2071/02—Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/0005—Condition, form or state of moulded material or of the material to be shaped containing compounding ingredients
    • B29K2105/0035—Medical or pharmaceutical agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/25—Solid
    • B29K2105/251—Particles, powder or granules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0088—Molecular weight
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor

Abstract

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and proces ses of manufacture, uses, and methods of treatment thereof.

Claims (164)

1. A process of preparing a solid oral extended release pharmaceutical dosage form, comprising at least the steps of:
(a) combining at least (1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000, and (2) at least one active agent, to form a composition;
(b) shaping the composition to form an extended release matrix formulation; and (c) curing said extended release matrix formulation comprising at least a curing step of subjecting the extended release matrix formulation to a temperature which is at least the softening temperature of said polyethylene oxide for a time period of at least about 1 minute.
2. The process of claim 1, wherein in step c) the extended release matrix formulation is subjected to a temperature which is at least the softening temperature of said polyethylene oxide for a time period of at least about 5 minutes.
3. The process of claim 1, wherein in step c) the extended release matrix formulation is subjected to a temperature which is at least the softening temperature of said polyethylene oxide for a time period of at least about 15 minutes.
4. The process of claim 1, 2 or 3, wherein in step b) the composition is shaped to form an extended release matrix formulation in the form of tablet.
5. The process of claim 4, wherein in step b) the composition is shaped by direct compression of said composition.
6. The process of any one of claims 1 to 5, wherein in step c) the extended release matrix formulation is subjected to a temperature of at least about 60 °C or at least about 62 °C, preferably at least about 68 °C, at least about 70 °C, at least about 72 °C or at least about 75 °C.
7. The process of claim 6, wherein the extended release matrix formulation is subjected to a temperature of from about 62 °C to about 90 °C, from about 65 °C to about 90 °C or from about 68 °C to about 90 °C.
8. The process of claim 6, wherein the extended release matrix formulation is subjected to a temperature of at least about 62 °C or at least about 68 °C for a time period of from about 1 minute to about 5 hours or from about 5 minutes to about 3 hours.
9. The process of claim 6, wherein the extended release matrix formulation is subjected to a temperature of at least about 62 °C or at least about 68 °C for a time period of at least about 15 minutes.
10. The process of claim 6, wherein the dosage form is subjected to a temperature of at least about 60 °C or at least about 62 °C, preferably at least about 68 °C, at least about 70 °C, at least about 72 °C or at least about 75 °C
or from about 62 °C to about 85 °C for a time period of at least about 15 minutes, at least about 30 minutes, at least about 60 minutes or at least about 90 minutes.
11. The process of any one of claims 1 to 10, wherein the extended release matrix formulation in step c) is subjected to a temperature of at least about 60 °C or at least about 62 °C, but less than about 90 °C or less than about 80 °C.
12. The process of any one of claims 1 to 11, wherein the curing step c) takes place in an oven with an inside temperature.
13. The process of claim 12, wherein the temperature of step c) is the target inside temperature of the oven and wherein the curing step starts when the inside temperature of the oven reaches said temperature, and the curing step ends either when the heating is stopped or at least reduced and the inside temperature of the oven subsequently drops below said temperature by more than about 10 °C or below about 62 °C, in a plateau-like temperature profile or when the inside temperature of the oven drops below said temperature in a parabolic or triangular temperature profile.
14. The process of claim 13, wherein the temperature profile during the curing step shows a plateau-like form and wherein said temperature is preferably at least about 68 °C and the curing time is preferably in the range of from about 30 minutes to about 20 hours.
15. The process of any one of claims I to 11, wherein the curing step c) takes place in a convection curing device comprising an inlet air temperature, an exhaust air temperature and/or a temperature probe.
16. The process of claim 15, wherein the temperature of step c) is defined to be the target inlet air temperature and wherein the curing step starts when the inlet air temperature reaches said temperature and the curing step ends either when the heating is stopped or at least reduced and the inlet air temperature subsequently drops below said temperature by more than about 10 °C or below about 62 °C, in a plateau-like temperature profile or when the inlet air temperature drops below said temperature in a parabolic or triangular temperature profile.
17. The process of claim 16, wherein the temperature profile during the curing step shows a plateau-like form and wherein said temperature is preferably at least about 72 °C and the curing time is preferably in the range of from about 15 minutes to about 2 hours.
18. The process of claim 15, wherein the temperature of step c) is the target exhaust air temperature and wherein the curing step starts when the exhaust air temperature reaches said temperature and the curing step ends either when the heating is stopped or at least reduced and the exhaust air temperature subsequently drops below said temperature by more than about 10 °C or below about 62 °C, in a plateau-like temperature profile or when the exhaust air temperature drops below said temperature in a parabolic or triangular temperature profile.
19. The process of claim 18, wherein the temperature profile during the curing step shows a plateau-like form and wherein said temperature is preferably at least about 68 °C and the curing time is preferably in the range of from about 1 minute to about 2 hours.
20. The process of claim 15, wherein the temperature of step c) is the target temperature of the extended release matrix formulations and wherein the curing step starts when the temperature of the extended release matrix formulations reaches said temperature and the curing step ends either when the heating is stopped or at least reduced and the temperature of the extended release matrix formulations subsequently drops below said temperature by more than about 10 °C or below about 62 °C, in a plateau-like temperature profile or when the temperature of the extended release matrix formulations drops below said temperature in a parabolic or triangular temperature profile.
21. The process of claim 15, wherein the temperature of step c) is the target temperature measured using a temperature probe and wherein the curing step starts when the temperature measured using the temperature probe reaches said temperature and the curing step ends either when the heating is stopped or at least reduced and the temperature measured using the temperature probe subsequently drops below said temperature by more than about 10 °C or below about 62 °C, in a plateau-like temperature profile or when the temperature measured using the temperature probe drops below said temperature in a parabolic or triangular temperature profile.
22. The process of claim 21, wherein the temperature profile during the curing step shows a plateau-like form and wherein said temperature is preferably at least about 68°C and the curing time is preferably in the range of from about 15 minutes to about 2 hours.
23. The process of any one of claims 1 to 11 and 15 to 22, wherein the curing step c) takes place in a bed of free flowing extended release matrix formulations.
24. The process of claim 23, wherein the curing takes place in a coating pan.
25. The process of any one of claims 1 to 24, comprising a further step of coating the cured extended release matrix formulation.
26. The process of claim 25, comprising the steps of:
(a) combining at least (1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000, and (2) at least one active agent, to form a composition;
(b) shaping said composition to form the extended release matrix formulation in the form of a tablet by direct compression;

(c) curing said tablet by - subjecting a bed of free flowing tablets to a temperature from about 62°C to about 90°C for a time period of at least about 1 minute in a coating pan and - subsequently cooling the bed of free flowing tablets to a temperature of below about 50 °C;
and subsequently (d) coating the dosage form in said coating pan.
27. A process of preparing a solid oral extended release pharmaceutical dosage form, comprising at least the steps of:
(a) combining at least (1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000, and (2) at least one active agent, to form a composition;
(b) shaping the composition to form an extended release matrix formulation; and (c) curing said extended release matrix formulation comprising at least a curing step wherein said polyethylene oxide at least partially melts.
28. The process of claim 27, wherein in step b) the composition is shaped to form an extended release matrix formulation in the form of tablet.
29. The process of claim 28, wherein in step b) the composition is shaped by direct compression of said composition.
30. The process of claim 29, wherein at least about 20%, at least about 40% or at least about 75% of the high molecular weight polyethylene oxide melts.
31. The process of claim 30, wherein about 100% of the high molecular weight polyethylene oxide melts.
32. The process of any one of claims 27 to 31, wherein the curing step c) takes place in an oven.
33. The process of any one of claims 27 to 31, wherein the curing step c) takes place in a convection curing device.
34. The process of any one of claims 27 to 31, wherein the curing step c) takes place in a bed of free flowing extended release matrix formulations.
35. The process of claim 34, wherein the curing takes place in a coating pan.
36. The process of any one of claims 27 to 35, comprising a further step of coating the cured extended release matrix formulation.
37. The process of any one of claims 1 to 36, wherein the active agent is an opioid analgesic.
38. The process of claim 37 wherein the opioid analgesic is selected from the group of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl and derivatives, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
39. The process of claim 37, wherein the opioid analgesic is selected from the group of codeine, morphine, oxycodone, hydrocodone, hydromorphone, or oxymorphone or pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
40. The process of claim 39, wherein the opioid analgesic is oxycodone hydrochloride and the dosage form comprises from about 5 mg to about 500 mg of oxycodone hydrochloride.
41. The process of claim 40, wherein the dosage form comprises 5 mg, 7.5 mg, 10mg, 15 mg, 20 mg, 30 mg, 40 mg, 45 mg, 60 mg, or 80 mg, 90 mg, 120mgor 160 mg of oxycodone hydrochloride.
42. The process of any one of claims 39 to 41, wherein the active agent is oxycodone hydrochloride and the oxycodone hydrochloride has a 14-hydroxycodeinone level of less than about 25 ppm, preferably of less than about 15 ppm, less than about 10 ppm, or less than about 5 ppm.
43. The process of claim 37, wherein the opioid analgesic is oxymorphone hydrochloride and the dosage form comprises from about 1 mg to about 500 mg of oxymorphone hydrochloride.
44. The process of claim 43, wherein the dosage form comprises 5 mg, 7.5 mg, mg, 15 mg, 20 mg, 30, mg, 40 mg, 45 mg, 60 mg, or 80 mg, 90 mg, 120 mg or 160 mg of oxymorphone hydrochloride.
45. The process of claim 37, wherein the opioid analgesic is hydromorphone hydrochloride and the dosage form comprises from about 1 mg to about 100 mg of hydromorphone hydrochloride.
46. The process of claim 45, wherein the dosage form comprises 2 mg, 4 mg, 8 mg, 12 mg, 16 mg, 24 mg, 32 mg, 48 mg or 64 mg of hydromorphone hydrochloride.
47. The process of any one of claims 1 to 46, wherein the at least one polyethylene oxide has, based on rheological measurements, an approximate molecular weight of from 2,000,000 to 8,000,000.
48. The process of claim 47, wherein the at least one polyethylene oxide has, based on rheological measurements, an approximate molecular weight of 2,000,000, 4,000,000, 7,000,000 or 8,000,000.
49. The process of any one of claims 1 to 48, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000.
50. The process of claim 49, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate - molecular weight of from 100,000 to 900,000.
51. The process of claim 50, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 100,000.
52. The process of any one of claims 1 to 51, wherein the overall content of polyethylene oxide in the composition is at least about 80 % (by wt).
53. The process of any one of claims 1 to 52, wherein the active agent is oxycodone hydrochloride and the overall content of oxycodone hydrochloridein the composition is more than about 5% (by wt)
54. The process of any one of claims 1 to 53, wherein the content in the composition of the at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000 is at least about 80 % (by wt).
55. The process of any one of claims 1 to 54, wherein the composition comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000 and at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000, wherein the composition comprises at least about 10 %
(by wt) or at least about 20 % (by wt) of the polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000.
56. The process of claim 55, wherein the dosage form is subjected to a temperature of less than about 80 °C or less than about 77 °C.
57. The process of any one of claims 1 to 56, wherein the curing step c) leads to a decrease in the density of the extended release matrix formulation.
58. The process of claim 57, wherein the density of the cured extended release matrix formulation in comparison to the density of the uncured extended release matrix formulation decreases by at least about 0.5%, preferably at least about 0.7%.
59. A solid oral extended release pharmaceutical dosage form obtainable by a process according to any one of claims 1 to 58.
60. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation comprising an active agent in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or of the individual multi particulate after the flattening which corresponds to no more than about 60 %
of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the flattened multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, characterized by the percent amount of active agent released at 0.5 hours of dissolution that deviates no more than about 20 % points from the corresponding in-vitro dissolution rate of a non-flattened reference tablet or reference multi particulates.
61. The solid oral extended release pharmaceutical dosage form of claim 60, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 50 %, or no more than about 40%, or no more than about 30%, or no more than about 20%, or no more than about 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, characterized by the percent amount of active agent released at 0.5 hours of dissolution that deviates no more than about 20 % points or no more than about 15 % points from the corresponding in-vitro dissolution rate of a non-flattened reference tablet or reference multi particulates.
62. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation comprising an active agent in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or of the individual multi particulate after the flattening which corresponds to no more than about 60 %
of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the flattened multi particulates and the non-flattened reference tablet or reference multi particulates provide an in-vitro dissolution rate, which when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, is between 5 and 40% (by wt) active agent released after 0.5 hours.
63. The solid oral extended release pharmaceutical dosage form of claim 62, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 50 %, or no more than about 40%, or no more than about 30%, or no more than about 20%, or no more than about 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the flattened multi particulates and the non-flattened reference tablet or reference multi particulates provide an in-vitro dissolution rate, which when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, is between 5 and 40% (by wt) active agent released after 0.5 hours or is between 5 and 30% (by wt) active agent released after 0.5 hours or is between 5 and 20% (by wt) active agent released after 0.5 hours or is between 10 and 18% (by wt) active agent released after 0.5 hours.
64. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation comprising an active agent in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 60% of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the flattened or non flattened multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40%

ethanol at 37° C, characterized by the percent amount of active agent released at 0.5 hours of dissolution that deviates no more than about 20 % points from the corresponding in-vitro dissolution rate measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37°
C without ethanol, using a flattened and non flattened reference tablet or flattened and non flattened reference multi particulates, respectively.
65. The solid oral extended release pharmaceutical dosage form of claim 64, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 60%, or no more than about 50%, or no more than about 40%, or no more than about 30%, or no more than about 20%, or no more than about 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the individual multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40% ethanol at 37° C, characterized by the percent amount of active agent released at 0.5 hours of dissolution that deviates no more than about 20 % points or no more than about 15 % points from the corresponding in-vitro dissolution rate measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C without ethanol, using a flattened and a non flattened reference tablet or reference multi particulates, respectively.
66. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation comprising an active agent in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 60%
of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the flattened or non flattened multi particulates provide an in-vitro dissolution rate, which when measured in a USP
Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40% or 0% ethanol at 37° C, is between 5 and 40% (by wt) active agent released after 0.5 hours.
67. The solid oral extended release pharmaceutical dosage form of claim 66, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than about 50%, or no more than about 40%, or no more than about 30%, or no more than about 20%, or no more than about 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the individual multi particulates provide an in-vitro dissolution rate, which when measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40% or 0% ethanol at 37° C, is between 5 and 40% (by wt) active agent released after 0.5 hours or is between 5 and 30% (by wt) active agent released after 0.5 hours or is between 5 and 20% (by wt) active agent released after 0.5 hours or is between 10 and 18% (by wt) active agent released after 0.5 hours.
68. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) at least one active agent selected from opioid analgesics; and wherein the composition comprises at least about 80 % (by wt) polyethylene oxide.
69. The solid oral extended release pharmaceutical dosage form of claim 68, wherein the opioid analgesic is oxycodone hydrochloride or hydromorphone hydrochloride and the composition comprises more than 5% (by wt) of the oxycodone hydrochloride or hydromorphone hydrochloride.
70. The solid oral extended release pharmaceutical dosage form of claim 68, wherein the composition comprises at least about 80 % (by wt) polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000.
71. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:

(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 10 mg oxycodone hydrochloride; and wherein the composition comprises at least about 85 % (by wt) polyethylene oxide.
72. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 15 mg or 20 mg oxycodone hydrochloride; and wherein the composition comprises at least about 80 % (by wt) polyethylene oxide.
73. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 40 mg oxycodone hydrochloride; and wherein the composition comprises at least about 65 % (by wt) polyethylene oxide.
74. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 60 mg or 80 mg oxycodone hydrochloride; and wherein the composition comprises at least about 60 % (by wt) polyethylene oxide.
75. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 8 mg hydromorphone hydrochloride; and wherein the composition comprises at least about 94 % (by wt) polyethylene oxide.
76. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 12 mg hydromorphone hydrochloride; and wherein the composition comprises at least about 92 % (by wt) polyethylene oxide.
77. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) 32 mg hydromorphone hydrochloride; and wherein the composition comprises at least about 90 % (by wt) polyethylene oxide.
78. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprsing a composition comprising at least:
(1) at least one active agent selected from opioid analgesics;
(2) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (3) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000.
79. The solid oral extended release pharmaceutical dosage form of claim 78, wherein the composition comprises at least about 80 % (by wt) of polyethylene oxide.
80. The solid oral extended release pharmaceutical dosage form of claim 78, wherein the composition comprises at least:
1. 15 to 30 % (by wt) of polyethylene oxide having, based on rheological measurements, a molecular weight of at least 1,000,000; and 65 to 80 % (by wt) polyethylene oxide having, based on rheological measurements, a molecular weight of less than 1,000,000; or 2. at least about 20% (by wt) or at least about 30 % (by wt) or at least about 50 % (by wt) of polyethylene oxide having, based on rheological measurements, a molecular weight of at least 1,000,000.
81. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, a molecular weight of at least 800,000; and (2) at least one active agent selected from opioid analgesics; and wherein the composition comprises at least about 80 % (by wt) polyethylene oxide.
82. The solid oral extended release pharmaceutical dosage form of claim 81, wherein the composition comprises at least one polyethylene oxide having, based on rheological measurements, a molecular weight of at least 900,000.
83. The solid oral extended release pharmaceutical dosage form of anyone of claims 59 to 82, wherein the density of the extended release matrix formulation is equal to or less than about 1.20 g/cm, preferably equal to or less than about 1.19 g/cm3.
84. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) at least one active agent; and wherein the extended release matrix formulation when subjected to an indentation test has a cracking force of at least about 110 N.
85. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) at least one active agent; and wherein the extended release matrix formulation when subjected to an indentation test has a "penetration depth to crack distance" of at least about 1.0 mm.
86. The solid oral extended release pharmaceutical dosage form of any one of claims 84 and 85, wherein the extended release matrix formulation has a cracking force of at least about 120 N, at least about 130 N or at least about 140 N and/or a "penetration depth to crack" distance of at least about 1.2 mm, preferably of at least about 1.4 mm, at least about 1.5 mm or at least about 1.6 mm.
87. The solid oral extended release pharmaceutical dosage form of any one of claims 84 and 85, wherein the extended release matrix formulation resists a work of at least about 0.06 J without cracking.
88. The solid oral extended release pharmaceutical dosage form of anyone of claims 60, 62, 64, 66, 68, 71-78, 81, 84 and 85, wherein the extended release matrix formulation after having been stored at 25 °C
and 60 % relative humidity (RH) for at least 1 month provides a dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, characterized by the percent amount of active agent released at 1, 4 and 12 hours of dissolution that deviates no more than about 15 % points from the corresponding in-vitro dissolution rate of a reference formulation prior to storage.
89. The solid oral extended release pharmaceutical dosage form of claim 88, wherein the extended release matrix formulation has been stored at 40 °C and 75 % relative humidity (RH).
90. The solid oral extended release pharmaceutical dosage form of anyone of claims 60, 62, 64, 66, 68, 71-78, 81, 84 and 85, wherein the extended release matrix formulation after having been stored at 25 °C
and 60 % relative humidity (RH) for at least 1 month contains an amount of the at least one active agent in % (by wt) relative to the label claim of the active agent for the extended release matrix formulation that deviates no more than about 10 %
points from the corresponding amount of active agent in % (by wt) relative to the label claim of the active agent for the extended release matrix formulation of a reference formulation prior to storage.
91. The solid oral extended release pharmaceutical dosage form of claim 90, wherein the extended release matrix formulation has been stored at 40 °C and 75 %
relative humidity (RH).
92. The solid oral extended release pharmaceutical dosage form of anyone of claims 60, 62, 64, 66, 68, 71-78, 81, 84 and 85, wherein the dosage provides a dissolution rate, which when measured in a USP
Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, is between 12.5 and 55% (by wt) active released after 1 hour, between 25 and 65% (by wt) active released after 2 hours, between 45 and 85%
(by wt) active released after 4 hours and between 55 and 95% (by wt) active released after 6 hours.
93. The solid oral extended release pharmaceutical dosage form of anyone of claims 60, 62, 64, 66, 68, 71-78, 81, 84 and 85, wherein the active agent is oxycodone hydrochloride and wherein the dosage form when tested in a comparative clinical study is bioequivalent to the commercial product OxyContin.TM..
94. The solid oral extended release pharmaceutical dosage form of anyone of claims 60, 62, 64, 66, 68, 71-78, 81, 84 and 85, wherein the active agent is oxycodone hydrochloride and wherein a dosage form comprising 10 mg of oxycodone hydrochloride when tested in a comparative clinical study is bioequivalent to a reference tablet containing 10 mg of oxycodone hydrochloride in a matrix formulation containing:
a) Oxycodone hydrochloride: 10.0 mg/tablet b) Lactose (spray-dried): 69.25 mg/tablet c) Povidone : 5.0 mg/tablet d) Eudragit® RS 30D (solids) : 10.0 mg/tablet e) Triacetin®: 2.0 mg/tablet f) Stearyl alcohol: 25.0 mg/tablet g) Talc: 2.5 mg/tablet h) Magnesium Stearate: 1.25 mg/tablet;
and wherein the reference tablet is prepared by the following steps:
1. Eudragit® RS 30D and Triacetin® are combined while passing through a 60 mesh screen, and mixed under low shear for approximately 5 minutes or until a uniform dispersion is observed.
2. Oxycodone HCl, lactose, and povidone are placed into a fluid bed granulator/dryer (FBD) bowl, and the suspension sprayed onto the powder in the fluid bed.
3. After spraying, the granulation is passed through a #12 screen if necessary to reduce lumps.
4. The dry granulation is placed in a mixer.
5. In the meantime, the required amount of stearyl alcohol is melted at a temperature of approximately 70 °C.
6. The melted stearyl alcohol is incorporated into the granulation while mixing.
7. The waxed granulation is transferred to a fluid bed granulator/dryer or trays and allowed to cool to room temperature or below.
8. The cooled granulation is then passed through a #12 screen.
9. The waxed granulation is placed in a mixer/blender and lubricated with the required amounts of talc and magnesium stearate for approximately 3 minutes.
10. The granulate is compressed into 125 mg tablets on a suitable tableting machine.
95. The extended release dosage form of claims 84 to 94, wherein the composition comprises at least about 80 % (by wt) of polyethylene oxide.
96. The extended release dosage form of claim 95, wherein the composition comprises at least about 80 % (by wt) polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000.
97. The extended release dosage form of any one of claims 60 to 96, wherein the active agent is an opioid analgesic.
98. The extended release dosage form of claim 97, wherein the opioid analgesic is selected from the group of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl and derivatives, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
99. The extended release dosage form of claim 97, wherein the opioid analgesic is selected from the group of codeine, morphine, oxycodone, hydrocodone, hydromorphone, or oxymorphone or pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
100. The extended release dosage form of claim 98, wherein the opioid analgesic is oxycodone hydrochloride and the dosage form comprises from about 5 mg to about 500 mg of oxycodone hydrochloride.
101. The extended release dosage form of claim 100, wherein the dosage form comprises 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30, mg, 40 mg, 45 mg, 60 mg, or mg, 90 mg, 120 mg or 160 mg of oxycodone hydrochloride.
102. The extended release dosage form of claim 97, wherein the opioid analgesic is oxycodone hydrochloride having a 14-hydroxycodeinone level of less than about 25 ppm, preferably of less than about 15 ppm, less than about 10 ppm, or less than about 5 ppm.
103. The extended release dosage form of claim 97, wherein the opioid analgesic is oxymorphone hydrochloride and the dosage form comprises from about 1 mg to about 500 mg of oxymorphone hydrochloride.
104. The extended release dosage form of claim 103, wherein the dosage form comprises 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 45 mg, 60 mg, or 80 mg, 90 mg, 120 mg or 160 mg of oxymorphone hydrochloride.
105. The extended release dosage form of claim 97, wherein the opioid analgesic is hydromorphone hydrochloride and the dosage form comprises from about 1 mg to about 100 mg of hydromorphone hydrochloride.
106. The extended release dosage form of claim 105, wherein the dosage form comprises 2 mg, 4 mg, 8 mg, 12 mg, 16 mg, 24 mg, 32 mg, 48 mg or 64 mg of hydromorphone hydrochloride.
107. The extended release dosage form of any one of claims 60 to 106, which is in the form of a tablet formed by direct compression of the composition and cured by at least subjecting said tablet to a temperature of at least about 60 °C or at least about 62 °C for a time period of at least about 1 minute, preferably at least about 5 minutes or at least about 15 minutes.
108. The extended release dosage form of any one of claims 60 to 107, which is in the form of a tablet and which is over coated with a polyethylene oxide powder layer to form a tablet that has a core tablet and a layer of polyethylene oxide surrounding the core tablet.
109. The extended release dosage form of any one of claims 60 to 107, which is in the form of a stacked bi or multi layered tablet, wherein one of the layers contains an extended release formulation and one of the other layers contains an immediate release formulation.
110. The extended release dosage form of claim 109, wherein the extended release formulation and the immediate release formulation contain the same or different active agents.
111. The extended release dosage form of claim 109, wherein the extended release formulation comprises an opioid analgesic and the immediate release formulation comprises a non opioid analgesic.
112. A method of treatment wherein a dosage form according to any one of claims 60 to 111 is administered for treatment of pain to a patient in need thereof, wherein the dosage form comprises an opioid analgesic.
113. Use of a dosage form according to any one of claims 60 to 111 for the manufacture of a medicament for the treatment of pain, wherein the dosage form comprises an opioid analgesic.
114. Use of high molecular weight polyethylene oxide that has, based on rheological measurements, a molecular weight of at least 1,000,000, as matrix forming material in the manufacture of a solid extended release oral dosage form comprising an active agent selected from opioids for imparting to the solid extended release oral dosage form resistance to alcohol extraction.
115. A process of preparing a solid oral extended release pharmaceutical dosage form, comprising at least the steps of:
(a) combining at least (1) at least one polyethylene oxide having, based on rheological measurements, a molecular weight of at least 1,000,000, and (2) at least one active agent, to form a composition;
(b) shaping the composition to form an extended release matrix formulation; and (c) curing said extended release matrix formulation comprising at least a curing step of subjecting the extended release matrix formulation to a temperature which is at least the softening temperature of said polyethylene oxide for a time period of at least 5 minutes.
116. The process of claim 115, wherein the composition is shaped to form an extended release matrix formulation in the form of tablet.
117. The process of claim 116, wherein the composition is shaped by direct compression of said composition.
118. The process of any one of claims 115 to 117, wherein in step c) the extended release matrix formulation is subjected to a temperature of at least 60 °C.
119. The process of claim 118 wherein the extended release matrix formulation is subjected to a temperature of from 65 °C to 90 °C.
120. The process of claim 118, wherein the extended release matrix formulation is subjected to a temperature at of least 60 °C or form 65 °C to 90 °C for a time period of at least 15 minutes or at least 30 minutes.
121. The process of claim 118, wherein the dosage form is subjected to a temperature of at least 60 °C or from 65 °C to 85 °C for a time period of at least 60 minutes, at least 75 minutes, at least 90 minutes or for 120 minutes.
122. The process of any one of claims 115 to 121, wherein the extended release matrix formulation in step c) is subjected to a temperature of at least 60 °C, but less than 90 °C or less than 80 °C.
123. The process of any one of claims 115 to 122, wherein the curing step c) takes place in an oven.
124. The process of any one of claims 115 to 122, wherein the curing step c) takes place in a bed of free flowing extended release matrix formulations.
125. The process of claim 124, wherein the curing takes place in a coating pan.
126. The process of any one of claims 115 to 125, comprising a further step of coating the cured extended release matrix formulation.
127. The process of claim 126, comprising the steps of:
(a) combining at least (1) at least one polyethylene oxide having, based on rheological measurements, a molecular weight of at least 1,000,000, and (2) at least one active agent, to form a composition;
(b) shaping said composition to form the extended release matrix formulation in the form of a tablet by direct compression;
(c) curing said tablet by - subjecting a bed of free following tablets to a temperature from 70°C

to 90°C for a time period of at least 30 minutes in a coating pan and - subsequently cooling the bed of free flowing tablets to a temperature of below 50 °C;
and subsequently (d) coating the dosage form in said coating pan.
128. The process of any one of claims 115 to 127, wherein the active agent is an opioid analgesic.
129. The process of claim 128 wherein the opioid analgesic is selected from the group of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl and derivatives, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
130. The process of claim 128, wherein the opioid analgesic is selected from the group of codeine, morphine, oxycodone, hydrocodone, hydromorphone, or oxymorphone or pharmaceutically acceptable salts, hydrates and solvates thereof, mixtures of any of the foregoing.
131. The process of claim 128, wherein the opioid analgesic is oxycodone hydrochloride and the dosage form comprises from 5 mg to 500 mg of oxycodone hydrochloride.
132. The process of claim 131 wherein the dosage form comprises 5 mg, 10 mg, 15 mg, 20 mg, 30, mg, 40 mg, 45 mg, 60 mg, or 80 mg, 90 mg, 120 mg or 160 mg oxycodone hydrochloride.
133. The process of claim 128, wherein the opioid analgesic is oxymorphone hydrochloride and the dosage form comprises from 1 mg to 500 mg of oxymorphone hydrochloride.
134. The process of claim 133 wherein the dosage form comprises 5 mg, 10 mg, 15 mg, 20 mg, 30, mg, 40 mg, 45 mg, 60 mg, or 80 mg, 90 mg, 120 mg or 160 mg oxymorphone hydrochloride.
135. The process of claim 128, wherein the opioid analgesic is hydromorphone hydrochloride and the dosage form comprises from 1 mg to 100 mg of hydromorphone hydrochloride.
136. The process of claim 135, wherein the dosage form comprises 2 mg, 4 mg, 8 mg, 12 mg, 16 mg, 24 mg, 32 mg, 48 mg or 64 mg hydromorphone hydrochloride.
137. The process of any one of claims 115 to 136, wherein the at least one polyethylene oxide has, based on rheological measurements, an approximate molecular weight of from 2,000,000 to 8,000,000.
138. The process of claim 136, wherein the at least one polyethylene oxide has, based on rheological measurements, an approximate molecular weight of 2,000,000, 4,000,000, 7,000,000 or 8,000,000.
139. The process of any one of claims 115 to 138, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000.
140. The process of claim 139, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of from 100,000 to 900,000.
141. The process of claim 139, wherein the composition further comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 100,000.
142. The process of any one of claims 115 to 141, wherein the overall content of polyethylene oxide in the composition is at least 80 % (by wt).
143. The process of any one of claims 115 to 142, wherein the content in the composition of the at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000 is at least 80 % (by wt).
144. The process of any one of claims 115 to 143, wherein the composition comprises at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000 and at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000, wherein the composition comprises at least % (by wt) or at least 20 % (by wt) of the polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000.
145. The process of claim 144, wherein the dosage form is subjected to a temperature of less than 80 °C or less than 77 °C.
146. A solid oral extended release pharmaceutical dosage form obtainable by a process according to any one of claims 115 to 145.
147. A solid oral extended release pharmaceutical dosage form comprising a extended release matrix formulation in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or of the individual multi particulate after the flattening which corresponds to no more than 60 % of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the flattened multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, characterized by the percent amount of active released at 0.5 hours of dissolution that deviates no more than 20 %
points from the corresponding in-vitro dissolution rate of a non-flattened reference tablet or reference multi particulates.
148. The solid oral extended release pharmaceutical dosage form of claim 147, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than 50 %, or no more than 40%, or no more than 30%, or no more than 20%, or no more than 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein said flattened tablet or the multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C, characterized by the percent amount of active released at 0.5 hours of dissolution that deviates no more than 20 % points or no more than 15 %
points from the corresponding in-vitro dissolution rate of a non-flattened reference tablet or reference multi particulates.
149. A solid oral extended release pharmaceutical dosage form comprising a extended release matrix formulation in the form of a tablet or multi particulates, wherein the tablet or the individual multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than 60% of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the flattened or non flattened multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40% ethanol at 37° C, characterized by the percent amount of active released at 0.5 hours of dissolution that deviates no more than 20 % points from the corresponding in-vitro dissolution rate measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C without ethanol, using a flattened and non flattened reference tablet or flattened and non flattened reference multi particulates, respectively.
150. The solid oral extended release pharmaceutical dosage form of claim 149, wherein the tablet or the multi particulates can at least be flattened without breaking, characterized by a thickness of the tablet or the individual multi particulate after the flattening which corresponds to no more than 60%, or no more than 50%, or no more than 40%, or no more than 30%, or no more than 20%, or no more than 16% of the thickness of the tablet or the individual multi particulate before flattening, and wherein the flattened or non flattened tablet or the individual multi particulates provide an in-vitro dissolution rate, when measured in a USP Apparatus 1(basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40%

ethanol at 37° C, characterized by the percent amount of active released at 0.5 hours of dissolution that deviates no more than 20 % points or no more than 15 %
points from the corresponding in-vitro dissolution rate measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37°
C without ethanol, using a flattened and a non flattened reference tablet or reference multi particulates, respectively.
151. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (2) at least one active agent; and wherein the composition comprises at least 80 % (by wt) polyethylene oxide.
152. The solid oral extended release pharmaceutical dosage form of claim 151, wherein the composition comprises at least 80 % (by wt) polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000.
153. A solid oral extended release pharmaceutical dosage form comprising an extended release matrix formulation, the extended release matrix formulation comprising a composition comprising at least:
(1) at least one active agent;
(2) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000;
and (3) at least one polyethylene oxide having, based on rheological measurements, a molecular weight of less than 1,000,000.
154. The extended release dosage form of claim 153, wherein the composition comprises at least 80 % (by wt) of polyethylene oxide.
155. The extended release dosage form of any one of claims 151 to 154, which is in the form of a tablet formed by direct compression of the composition and cured by at least subjecting said tablet to a temperature of the least 60 °C for a time period of at least 15 minutes.
156. The extended release dosage form of any one of claims 146 to 155, which is in the form of a tablet and which is over coated with a polyethylene oxide powder layer to form a tablet that has a core tablet and a layer of polyethylene oxide surrounding the core tablet.
157. The extended release dosage form of any one of claims 146 to 155, which is in the form of a stacked bi or multi layered tablet, wherein one of the layers contains an extended release formulation and one of the other layers contains an immediate release formulation.
158. The extended release dosage form of claim 157, wherein the extended release formulation and the immediate release formulation contain the same or different active agents.
159. The extended release dosage form of claim 157, wherein the extended release formulation comprises an opioid analgesic and the immediate release formulation comprises a non opioid analgesic..
160. A method of treatment wherein a dosage form according to any one of claims 146 to 155 is administered for treatment of pain to a patient in need thereof, wherein the dosage form comprises an opioid analgesic.
161. Use of a dosage form according to any one of claims 146 to 155 for the manufacture of a medicament for the treatment of pain, wherein the dosage form comprises an opioid analgesic.
162. Use of high molecular weight polyethylene oxide that has, based on rheological measurements, a molecular weight of at least 1,000,000, as matrix forming material in the manufacture of a solid extended release oral dosage form comprising an active selected from opioids for imparting to the solid extended release oral dosage form resistance to alcohol extraction.
163. The process of any one of claims 1 to 58 and 115 to 145, wherein the curing is conducted at atmospheric pressure.
164. The process of any one of claims 23, 24, 124 and 125, wherein magnesium stearate is added during or after the curing step.
CA2661573A 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic Active CA2661573C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2707204A CA2707204C (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US84024406P 2006-08-25 2006-08-25
US60/840,244 2006-08-25
PCT/IB2007/002515 WO2008023261A1 (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2707204A Division CA2707204C (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic

Publications (2)

Publication Number Publication Date
CA2661573A1 true CA2661573A1 (en) 2008-02-28
CA2661573C CA2661573C (en) 2010-10-26

Family

ID=38754532

Family Applications (2)

Application Number Title Priority Date Filing Date
CA2661573A Active CA2661573C (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic
CA2707204A Active CA2707204C (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA2707204A Active CA2707204C (en) 2006-08-25 2007-08-24 Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic

Country Status (42)

Country Link
US (62) US8894987B2 (en)
EP (11) EP2070538B1 (en)
JP (8) JP5069300B2 (en)
KR (8) KR20170118249A (en)
CN (9) CN102688213A (en)
AP (1) AP2009004770A0 (en)
AR (4) AR062511A1 (en)
AT (5) ATE489953T1 (en)
AU (1) AU2007287341B2 (en)
BR (2) BRPI0714539B8 (en)
CA (2) CA2661573C (en)
CL (3) CL2007002485A1 (en)
CO (1) CO6160317A2 (en)
CR (2) CR10691A (en)
CY (7) CY1110573T1 (en)
DE (5) DE602007002596D1 (en)
DK (11) DK2080514T3 (en)
DO (2) DOP2009000026A (en)
EA (3) EA023807B1 (en)
ES (11) ES2417334T3 (en)
GT (2) GT200900023BA (en)
HK (12) HK1133192A1 (en)
HR (11) HRP20090688T1 (en)
IL (10) IL197214A (en)
IN (1) IN2015DN01813A (en)
JO (2) JO2858B1 (en)
MA (1) MA30766B1 (en)
ME (7) ME01339B (en)
MX (2) MX360849B (en)
MY (3) MY161079A (en)
NZ (3) NZ574447A (en)
PE (5) PE20150340A1 (en)
PL (11) PL2082742T3 (en)
PT (11) PT2292230E (en)
RS (11) RS52798B (en)
SA (1) SA07280459B1 (en)
SI (11) SI2311459T1 (en)
TN (1) TN2009000059A1 (en)
TW (1) TWI341213B (en)
UA (2) UA104745C2 (en)
WO (1) WO2008023261A1 (en)
ZA (1) ZA200900755B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114659554A (en) * 2022-03-01 2022-06-24 安徽农业大学 Fault diagnosis method for biomass granulator

Families Citing this family (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030068375A1 (en) 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
US20040253310A1 (en) 2001-09-21 2004-12-16 Gina Fischer Morphine polymer release system
US20040234602A1 (en) 2001-09-21 2004-11-25 Gina Fischer Polymer release system
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US20040001889A1 (en) 2002-06-25 2004-01-01 Guohua Chen Short duration depot formulations
JP4865330B2 (en) 2002-12-13 2012-02-01 デュレクト コーポレーション Oral drug delivery system
ATE495732T1 (en) 2003-03-26 2011-02-15 Egalet As CONTROLLED RELEASE MORPHINE SYSTEM
DE10336400A1 (en) 2003-08-06 2005-03-24 Grünenthal GmbH Anti-abuse dosage form
DE102004032051A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
US20070048228A1 (en) * 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE102004020220A1 (en) * 2004-04-22 2005-11-10 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
DE102005005446A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Break-resistant dosage forms with sustained release
DE10361596A1 (en) 2003-12-24 2005-09-29 Grünenthal GmbH Process for producing an anti-abuse dosage form
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
US7201920B2 (en) 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
EP3326617A1 (en) 2004-06-12 2018-05-30 Collegium Pharmaceutical, Inc. Abuse-deterrent drug formulations
DE102004032049A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
DE102004032103A1 (en) * 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
PT2767292T (en) 2004-09-17 2016-11-23 Durect Corp Sustained local anesthetic composition containing saib
DE102005005449A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Process for producing an anti-abuse dosage form
AU2006254554B2 (en) * 2005-06-03 2011-11-24 Egalet Ltd A solid pharmaceutical composition with a first fraction of a dispersion medium and a second fraction of a matrix, the latter being at least partially first exposed to gastrointestinal fluids
US20070027105A1 (en) 2005-07-26 2007-02-01 Alza Corporation Peroxide removal from drug delivery vehicle
SA07280459B1 (en) * 2006-08-25 2011-07-20 بيورديو فارما إل. بي. Tamper Resistant Oral Pharmaceutical Dosage Forms Comprising an Opioid Analgesic
ES2388355T3 (en) 2006-11-03 2012-10-11 Durect Corporation Transdemic delivery systems comprising bupivacaine
DE102007011485A1 (en) 2007-03-07 2008-09-11 Grünenthal GmbH Dosage form with more difficult abuse
US8173666B2 (en) 2007-03-12 2012-05-08 Nektar Therapeutics Oligomer-opioid agonist conjugates
US10512644B2 (en) 2007-03-12 2019-12-24 Inheris Pharmaceuticals, Inc. Oligomer-opioid agonist conjugates
EP2155167A2 (en) 2007-06-04 2010-02-24 Egalet A/S Controlled release pharmaceutical compositions for prolonged effect
US20080318994A1 (en) * 2007-06-21 2008-12-25 Endo Pharmaceuticals, Inc. Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment
CN101801350A (en) 2007-08-13 2010-08-11 阿巴斯迪特宁医药有限公司 Abuse resistant drugs, using method and preparation method
WO2009088414A2 (en) 2007-12-06 2009-07-16 Durect Corporation Oral pharmaceutical dosage forms
US8383152B2 (en) 2008-01-25 2013-02-26 Gruenenthal Gmbh Pharmaceutical dosage form
US8372432B2 (en) 2008-03-11 2013-02-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
EP2262484B1 (en) * 2008-03-11 2013-01-23 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
HUE030803T2 (en) 2008-05-09 2017-06-28 Gruenenthal Gmbh Process for the preparation of an intermediate powder formulation and a final solid dosage form under usage of a spray congealing step
US20110165248A1 (en) * 2008-09-18 2011-07-07 Meridith Lee Machonis Pharmaceutical dosage forms comprising poly(e-caprolactone)
US20100260844A1 (en) 2008-11-03 2010-10-14 Scicinski Jan J Oral pharmaceutical dosage forms
ES2414856T3 (en) 2008-12-12 2013-07-23 Paladin Labs Inc. Narcotic drug formulations with decreased addiction potential
WO2010088911A1 (en) 2009-02-06 2010-08-12 Egalet A/S Pharmaceutical compositions resistant to abuse
NZ594207A (en) 2009-02-06 2013-03-28 Egalet Ltd Immediate release composition resistant to abuse by intake of alcohol
US20100280059A1 (en) * 2009-05-01 2010-11-04 Atley Pharmaceuticals, Inc. Compositions comprising an antihistamine, antitussive and decongestant in extended release formulations
JP2012525423A (en) * 2009-05-01 2012-10-22 アトリー ファーマシューティカルズ インコーポレイテッド Composition comprising antihistamine, antitussive and decongestant in sustained release preparation
NZ603579A (en) 2009-06-24 2014-02-28 Egalet Ltd Controlled release formulations
RU2555531C2 (en) 2009-07-22 2015-07-10 Грюненталь Гмбх Misuse protected dosage form for oxidation sensitive opioids
KR101738369B1 (en) 2009-07-22 2017-05-22 그뤼넨탈 게엠베하 Hot-melt extruded controlled release dosage form
WO2011026125A2 (en) * 2009-08-31 2011-03-03 Depomed, Inc. Gastric retentive pharmaceutical compositions for immediate and extended release of acetaminophen
EP3064064A1 (en) 2009-09-30 2016-09-07 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse
US10668060B2 (en) 2009-12-10 2020-06-02 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
US8597681B2 (en) 2009-12-22 2013-12-03 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9579285B2 (en) 2010-02-03 2017-02-28 Gruenenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
EP2568965A1 (en) 2010-05-10 2013-03-20 Euro-Celtique S.A. Combination of active loaded granules with additional actives
NZ700732A (en) 2010-05-10 2015-08-28 Euro Celtique Sa Pharmaceutical compositions comprising hydromorphone and naloxone
WO2011141489A1 (en) 2010-05-10 2011-11-17 Euro-Celtique S.A. Manufacturing of active-free granules and tablets comprising the same
AR081931A1 (en) 2010-06-15 2012-10-31 Gruenenthal Gmbh PHARMACEUTICAL COMBINATION
EP2611426B1 (en) 2010-09-02 2014-06-25 Grünenthal GmbH Tamper resistant dosage form comprising inorganic salt
AR082862A1 (en) 2010-09-02 2013-01-16 Gruenenthal Gmbh ALTERATION RESISTANT DOSAGE FORM INCLUDING AN ANIONIC POLYMER
AU2011342893A1 (en) 2010-12-13 2013-05-02 Purdue Pharma L.P. Controlled release dosage forms
CN104856966A (en) * 2010-12-22 2015-08-26 普渡制药公司 Coated tamper-resistant controlled release dosage form
EP2826468A1 (en) * 2010-12-22 2015-01-21 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
CN103327969A (en) 2010-12-23 2013-09-25 普渡制药公司 Tamper resistant solid oral dosage forms
HUE026981T2 (en) * 2011-03-25 2016-08-29 Purdue Pharma Lp Controlled release pharmaceutical dosage forms
US8858963B1 (en) 2011-05-17 2014-10-14 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
US8741885B1 (en) 2011-05-17 2014-06-03 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US9050335B1 (en) 2011-05-17 2015-06-09 Mallinckrodt Llc Pharmaceutical compositions for extended release of oxycodone and acetaminophen resulting in a quick onset and prolonged period of analgesia
AT511581A1 (en) 2011-05-26 2012-12-15 G L Pharma Gmbh ORAL RETARDANT FORMULATION
EA201400172A1 (en) 2011-07-29 2014-06-30 Грюненталь Гмбх SUSTAINABLE TO DESTRUCTION TABLET THAT PROVIDES IMMEDIATE RELEASE OF MEDICINES
AR087359A1 (en) 2011-07-29 2014-03-19 Gruenenthal Gmbh TEST ALTERATION TABLET PROVIDING IMMEDIATE RELEASE OF THE PHARMACO
US20140341984A1 (en) * 2011-09-16 2014-11-20 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
WO2013038268A1 (en) * 2011-09-16 2013-03-21 Purdue Pharma L.P. Tamper resistant immediate release formulations
MX356210B (en) * 2011-10-18 2018-05-18 Purdue Pharma Lp Acrylic polymer formulations.
EA201400590A1 (en) 2011-11-17 2014-11-28 Грюненталь Гмбх Resistance to fracture an oral pharmaceutical dosage form comprising a pharmacologically active ingredient opioid antagonist and / or a means, is disgusting, polyalkylene oxide and anionic polymers
EP2782558A4 (en) * 2011-11-22 2015-03-18 Watson Pharmaceuticals Inc Immediate release abuse deterrent tablet
TW201336529A (en) * 2011-12-09 2013-09-16 Purdue Pharma Lp Pharmaceutical dosage forms comprising poly( ε -caprolactone) and polyethylene oxide
EP2819656A1 (en) 2012-02-28 2015-01-07 Grünenthal GmbH Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer
MX362357B (en) 2012-04-18 2019-01-14 Gruenenthal Gmbh Tamper resistant and dose-dumping resistant pharmaceutical dosage form.
JP6067100B2 (en) 2012-04-18 2017-01-25 マリンクロッド エルエルシー Immediate release abuse deterrent pharmaceutical composition
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
CA2877183A1 (en) 2012-07-06 2014-01-09 Egalet Ltd. Abuse deterrent pharmaceutical compositions for controlled release
CA2877774C (en) 2012-07-12 2017-07-18 Mallinckrodt Llc Extended release, abuse deterrent pharmaceutical compositions
EP3446685A1 (en) 2012-11-30 2019-02-27 Acura Pharmaceuticals, Inc. Self-regulated release of active pharmaceutical ingredient
KR101840526B1 (en) 2013-02-05 2018-03-20 퍼듀 퍼머 엘피 Tamper resistant pharmaceutical formulations
US9572885B2 (en) 2013-03-15 2017-02-21 Durect Corporation Compositions with a rheological modifier to reduce dissolution variability
WO2014146093A2 (en) 2013-03-15 2014-09-18 Inspirion Delivery Technologies, Llc Abuse deterrent compositions and methods of use
JP6255474B2 (en) 2013-03-15 2017-12-27 マリンクロッド エルエルシー Abuse deterrent solid dosage form for immediate release with functional secant
US10751287B2 (en) 2013-03-15 2020-08-25 Purdue Pharma L.P. Tamper resistant pharmaceutical formulations
AR096439A1 (en) 2013-05-29 2015-12-30 Gruenenthal Gmbh DOSAGE METHOD RESISTING TO INDEED USE CONTAINING ONE OR MORE PARTICLES
JP6445537B2 (en) 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 Tamper-resistant dosage forms containing one or more particles
EA032465B1 (en) 2013-07-12 2019-05-31 Грюненталь Гмбх Tamper-resistant oral pharmaceutical dosage form containing ethylene-vinyl acetate polymer and process for the production thereof
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
NZ719087A (en) 2013-11-13 2017-12-22 Euro Celtique Sa 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
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
US10632113B2 (en) 2014-02-05 2020-04-28 Kashiv Biosciences, Llc Abuse-resistant drug formulations with built-in overdose protection
CA2943728C (en) 2014-03-26 2020-03-24 Sun Pharma Advanced Research Company Ltd. Abuse deterrent immediate release biphasic matrix solid dosage form
AU2015261060A1 (en) 2014-05-12 2016-11-03 Grunenthal Gmbh Tamper resistant immediate release capsule formulation comprising Tapentadol
CA2949422A1 (en) 2014-05-26 2015-12-03 Grunenthal Gmbh Multiparticles safeguarded against ethanolic dose-dumping
ES2963078T3 (en) 2014-07-03 2024-03-25 SpecGx LLC Abuse-deterrent immediate-release formulations comprising non-cellulosic polysaccharides
EP3169315B1 (en) 2014-07-17 2020-06-24 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US9132096B1 (en) 2014-09-12 2015-09-15 Alkermes Pharma Ireland Limited Abuse resistant pharmaceutical compositions
US10729685B2 (en) 2014-09-15 2020-08-04 Ohemo Life Sciences Inc. Orally administrable compositions and methods of deterring abuse by intranasal administration
US20160106737A1 (en) 2014-10-20 2016-04-21 Pharmaceutical Manufacturing Research Services, Inc. Extended Release Abuse Deterrent Liquid Fill Dosage Form
JP5888387B1 (en) * 2014-10-22 2016-03-22 ミツミ電機株式会社 Battery protection circuit, battery protection device, and battery pack
BR112017022856A2 (en) 2015-04-24 2018-07-17 Gruenenthal Gmbh tamper-proof fixed dose combination that provides rapid release of two drugs from particles
EP3285745A1 (en) 2015-04-24 2018-02-28 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
US20160310428A1 (en) 2015-04-24 2016-10-27 Grunenthal Gmbh Tamper-resistant fixed dose combination providing fast release of two drugs from different particles
US20160310486A1 (en) 2015-04-24 2016-10-27 Grünenthal GmbH Tamper-resistant fixed dose combination providing fast release of two drugs from particles and a matrix
US11103581B2 (en) 2015-08-31 2021-08-31 Acura Pharmaceuticals, Inc. Methods and compositions for self-regulated release of active pharmaceutical ingredient
JP2018526414A (en) 2015-09-10 2018-09-13 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 Protection against oral overdose with abuse-inhibiting immediate release formulations
WO2017059374A1 (en) * 2015-09-30 2017-04-06 Kashiv Pharma Llc Overdose protection and abuse deterrent immediate release drug formulation
US9861629B1 (en) 2015-10-07 2018-01-09 Banner Life Sciences Llc Opioid abuse deterrent dosage forms
US20180303757A1 (en) * 2015-10-23 2018-10-25 Kashiv Pharma Llc Enhanced abuse-deterrent formulations of oxycodone
WO2017139106A1 (en) 2016-02-08 2017-08-17 Mallinckrodt Llc Glucomannan containing pharmaceutical compositions with extended release and abuse deterrent properties
JP6323846B2 (en) * 2016-04-07 2018-05-16 塩野義製薬株式会社 Abuse prevention formulation containing opioid
US20170296476A1 (en) 2016-04-15 2017-10-19 Grünenthal GmbH Modified release abuse deterrent dosage forms
US10335405B1 (en) 2016-05-04 2019-07-02 Patheon Softgels, Inc. Non-burst releasing pharmaceutical composition
WO2017222575A1 (en) 2016-06-23 2017-12-28 Collegium Pharmaceutical, Inc. Process of making more stable abuse-deterrent oral formulations
US20180028670A1 (en) 2016-08-01 2018-02-01 Grünenthal GmbH Tamper resistant dosage form comprising an anionic polysaccharide
JP2019524761A (en) 2016-08-12 2019-09-05 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 Anti-modification preparation of ephedrine and its derivatives
DE202016105585U1 (en) * 2016-10-06 2017-01-23 L.B. Bohle Maschinen + Verfahren Gmbh Plant for the production of pharmaceutical tablets
USD857156S1 (en) * 2016-11-02 2019-08-20 Innovative Water Care, Llc Chemical tablet for aquatic systems
EP3554548A4 (en) 2016-12-19 2020-08-19 The Regents of The University of California Noncrushable pill formulatiions
KR102051132B1 (en) * 2017-03-17 2019-12-02 주식회사 종근당 Pharmaceutical composition for controlled release comprising Mirabegron or its salts
US10335375B2 (en) 2017-05-30 2019-07-02 Patheon Softgels, Inc. Anti-overingestion abuse deterrent compositions
WO2019003062A1 (en) * 2017-06-29 2019-01-03 Zenvision Pharma Llp Tamper-proof dosage form comprising pharmaceutically active agent
US10376471B2 (en) * 2017-07-10 2019-08-13 Gel Cap Technologies, LLC Dual release dosage form capsule and methods, devices and systems for making same
GB2571696B (en) 2017-10-09 2020-05-27 Compass Pathways Ltd Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced
WO2019073028A1 (en) 2017-10-13 2019-04-18 Grünenthal GmbH Modified release abuse deterrent dosage forms
JP7293209B2 (en) * 2017-10-20 2023-06-19 パーデュー、ファーマ、リミテッド、パートナーシップ Pharmaceutical dosage form
AU2018390826A1 (en) * 2017-12-20 2020-03-12 Purdue Pharma L.P. Abuse deterrent morphine sulfate dosage forms
US10624856B2 (en) 2018-01-31 2020-04-21 Dharma Laboratories LLC Non-extractable oral solid dosage forms
TW202002957A (en) 2018-02-09 2020-01-16 德商歌林達有限公司 Tamper resistant formulation of ephedrine and its derivatives comprising a conversion inhibitor
CA3111353A1 (en) * 2018-09-06 2020-03-12 Fachhochschule Nordwestschweiz Controlled drug release formulation
CA3112030A1 (en) 2018-09-25 2020-04-02 SpecGx LLC Abuse deterrent immediate release capsule dosage forms
WO2020070547A1 (en) 2018-10-05 2020-04-09 Clexio Biosciences Ltd. Dosage regime of esketamine for treating major depressive disorder
EP3860579A1 (en) 2018-10-05 2021-08-11 Clexio Biosciences Ltd. Dosage regime of esketamine for treating major depressive disorder
WO2020070706A1 (en) 2018-10-05 2020-04-09 Clexio Biosciences Ltd. Dosage regime of esketamine for treating major depressive disorder
EP3863617A1 (en) 2018-10-11 2021-08-18 Clexio Biosciences Ltd. Esketamine for use in treating major depressive disorder
WO2020079699A1 (en) * 2018-10-16 2020-04-23 M.O Advanced Technologies (Moat) Ltd Apparatus and method for prediction of tablet defects propensity
CN111251521B (en) * 2018-12-03 2022-07-22 沈欣 Method for preparing liquid bead pill
EP3698776A1 (en) 2019-02-19 2020-08-26 Grünenthal GmbH Tamper-resistant dosage form with immediate release and resistance against solvent extraction
CA3138100A1 (en) 2019-04-17 2020-10-22 Compass Pathfinder Limited Treatment of depression and other various disorders with psilocybin
CN110946086B (en) * 2019-12-04 2023-05-12 北京猫猫狗狗科技有限公司 Discharging device and discharging control method
WO2021137147A1 (en) 2019-12-30 2021-07-08 Clexio Biosciences Ltd. Dosage regime with esketamine for treating major depressive disorder
WO2021137148A1 (en) 2019-12-30 2021-07-08 Clexio Biosciences Ltd. Dosage regime with esketamine for treating neuropsychiatric or neurological conditions
CN115666621A (en) 2020-01-13 2023-01-31 度勒科特公司 Sustained release drug delivery systems with reduced impurities and related methods
USD943706S1 (en) * 2020-06-10 2022-02-15 Emily Florence Johns Shower steamer

Family Cites Families (297)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1485673A (en) * 1924-03-04 Ministrator
US1468805A (en) 1923-09-25 Htabtin ereund
US1479293A (en) 1924-01-01 Hiabtor fbettlid
US636438A (en) 1899-02-08 1899-11-07 Charles H Lovejoy Molder's chaplet.
US2654756A (en) 1949-10-20 1953-10-06 Mallinckrodt Chemical Works Process of preparing codeinone, dihydrocodeinone, and dihydromorphinone
US2772270A (en) 1954-10-21 1956-11-27 M J Lewenstein 14-hydroxymorphinone and 8, 14-dihydroxydihydromorphinone
US3096248A (en) 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3097144A (en) 1960-10-14 1963-07-09 Upjohn Co Heat-cured, polymeric, medicinal dosage film coatings containing a polyvinylpyrrolidone copolymer, polyethenoid acid, and polyethylene glycol
US3806603A (en) * 1969-10-13 1974-04-23 W Gaunt Pharmaceutical carriers of plasticized dried milled particles of hydrated cooked rice endosperm
US3885027A (en) 1971-04-12 1975-05-20 West Laboratories Inc Orally administered drug composition for therapy in the treatment of narcotic drug addiction
US3966747A (en) * 1972-10-26 1976-06-29 Bristol-Myers Company 9-Hydroxy-6,7-benzomorphans
US3888027A (en) 1973-07-30 1975-06-10 Kennametal Inc Arrangement for enhancing blade life
US3980766A (en) 1973-08-13 1976-09-14 West Laboratories, Inc. Orally administered drug composition for therapy in the treatment of narcotic drug addiction
US3941865A (en) * 1973-12-10 1976-03-02 Union Carbide Corporation Extrusion of ethylene oxide resins
DE2530563C2 (en) * 1975-07-09 1986-07-24 Bayer Ag, 5090 Leverkusen Analgesic drugs with reduced potential for abuse
GB1598458A (en) 1977-04-01 1981-09-23 Hoechst Uk Ltd Tableting of microcapsules
US4175119A (en) 1978-01-11 1979-11-20 Porter Garry L Composition and method to prevent accidental and intentional overdosage with psychoactive drugs
US4211681A (en) 1978-08-16 1980-07-08 Union Carbide Corporation Poly(ethylene oxide) compositions
CA1146866A (en) 1979-07-05 1983-05-24 Yamanouchi Pharmaceutical Co. Ltd. Process for the production of sustained release pharmaceutical composition of solid medical material
DE3002664C2 (en) 1980-01-25 1989-05-18 Titmus Eurocon Kontaktlinsen Gmbh & Co Kg, 8750 Aschaffenburg Soft contact lens
IL70071A (en) 1982-11-01 1987-12-31 Merrell Dow Pharma Multilayered sustained release pharmaceutical tablets having non-uniform distribution of active ingredient
US4501828A (en) * 1983-01-20 1985-02-26 General Technology Applications,Inc. Dissolving water soluble polymers
US4783337A (en) 1983-05-11 1988-11-08 Alza Corporation Osmotic system comprising plurality of members for dispensing drug
US4765989A (en) * 1983-05-11 1988-08-23 Alza Corporation Osmotic device for administering certain drugs
US4612008A (en) 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
FR2557459B1 (en) 1984-01-02 1986-05-30 Lhd Lab Hygiene Dietetique POLYCAPROLACTONE-BASED INERT MATRIX FOR ORAL ADMINISTRATION OF A MEDICAMENT, AND METHOD FOR PREPARING THE GALENIC FORM COMPRISING THE SAME
US4599342A (en) 1984-01-16 1986-07-08 The Procter & Gamble Company Pharmaceutical products providing enhanced analgesia
US4629621A (en) 1984-07-23 1986-12-16 Zetachron, Inc. Erodible matrix for sustained release bioactive composition
AU592065B2 (en) 1984-10-09 1990-01-04 Dow Chemical Company, The Sustained release dosage form based on highly plasticized cellulose ether gels
GB8507779D0 (en) 1985-03-26 1985-05-01 Fujisawa Pharmaceutical Co Drug carrier
US4616644A (en) 1985-06-14 1986-10-14 Johnson & Johnson Products, Inc. Hemostatic adhesive bandage
AU583639B2 (en) 1985-06-24 1989-05-04 Pitman-Moore Australia Limited Ingestible capsules
US4619988A (en) 1985-06-26 1986-10-28 Allied Corporation High strength and high tensile modulus fibers or poly(ethylene oxide)
EP0328775B1 (en) 1985-06-28 1993-10-20 Carrington Laboratories, Inc. Processes for preparation of aloe products, products produced thereby and compositions thereof
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
DE3689650T2 (en) 1985-12-17 1994-05-26 United States Surgical Corp High molecular weight bioabsorbable polymers and implants thereof.
US4764378A (en) 1986-02-10 1988-08-16 Zetachron, Inc. Buccal drug dosage form
US4713243A (en) 1986-06-16 1987-12-15 Johnson & Johnson Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
USRE33093E (en) 1986-06-16 1989-10-17 Johnson & Johnson Consumer Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
US4861598A (en) * 1986-07-18 1989-08-29 Euroceltique, S.A. Controlled release bases for pharmaceuticals
US4970075A (en) 1986-07-18 1990-11-13 Euroceltique, S.A. Controlled release bases for pharmaceuticals
EP0277289B8 (en) 1986-11-10 2003-05-21 Biopure Corporation Extra pure semi-synthetic blood substitute
US4892778A (en) * 1987-05-27 1990-01-09 Alza Corporation Juxtaposed laminated arrangement
US5019397A (en) * 1988-04-21 1991-05-28 Alza Corporation Aqueous emulsion for pharmaceutical dosage form
US5160743A (en) 1988-04-28 1992-11-03 Alza Corporation Annealed composition for pharmaceutically acceptable drug
US5162504A (en) 1988-06-03 1992-11-10 Cytogen Corporation Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients
US4960814A (en) 1988-06-13 1990-10-02 Eastman Kodak Company Water-dispersible polymeric compositions
US5350741A (en) 1988-07-30 1994-09-27 Kanji Takada Enteric formulations of physiologically active peptides and proteins
US5139790A (en) * 1988-10-14 1992-08-18 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US5004601A (en) * 1988-10-14 1991-04-02 Zetachron, Inc. Low-melting moldable pharmaceutical excipient and dosage forms prepared therewith
US5202128A (en) 1989-01-06 1993-04-13 F. H. Faulding & Co. Limited Sustained release pharmaceutical composition
US5330766A (en) 1989-01-06 1994-07-19 F. H. Faulding & Co. Limited Sustained release pharmaceutical composition
US5051222A (en) 1989-09-01 1991-09-24 Air Products And Chemicals, Inc. Method for making extrudable polyvinyl alcohol compositions
EP0418596A3 (en) 1989-09-21 1991-10-23 American Cyanamid Company Controlled release pharmaceutical compositions from spherical granules in tabletted oral dosage unit form
US5169645A (en) 1989-10-31 1992-12-08 Duquesne University Of The Holy Ghost Directly compressible granules having improved flow properties
US5200197A (en) * 1989-11-16 1993-04-06 Alza Corporation Contraceptive pill
GB8926612D0 (en) 1989-11-24 1990-01-17 Erba Farmitalia Pharmaceutical compositions
FR2664851B1 (en) * 1990-07-20 1992-10-16 Oreal METHOD OF COMPACTING A POWDER MIXTURE FOR OBTAINING A COMPACT ABSORBENT OR PARTIALLY DELITABLE PRODUCT AND PRODUCT OBTAINED BY THIS PROCESS.
SE9003904D0 (en) 1990-12-07 1990-12-07 Astra Ab METHOD FOR THE MANUFACTURE OF A PHARMACEUTICAL DOSAGE FORM
US5273758A (en) * 1991-03-18 1993-12-28 Sandoz Ltd. Directly compressible polyethylene oxide vehicle for preparing therapeutic dosage forms
WO1993006723A1 (en) 1991-10-04 1993-04-15 Olin Corporation Fungicide tablet
US5405366A (en) * 1991-11-12 1995-04-11 Nepera, Inc. Adhesive hydrogels having extended use lives and process for the preparation of same
US5266331A (en) 1991-11-27 1993-11-30 Euroceltique, S.A. Controlled release oxycodone compositions
US5656295A (en) * 1991-11-27 1997-08-12 Euro-Celtique, S.A. Controlled release oxycodone compositions
ATE140620T1 (en) 1991-12-05 1996-08-15 Mallinckrodt Veterinary Inc GLASSY CARBOHYDRATE MATRICE FOR ADMINISTRATION OF DELAYED RELEASE MEDICATIONS
EP0617612B1 (en) 1991-12-18 1997-09-10 Warner-Lambert Company A process for the preparation of a solid dispersion
US5968551A (en) 1991-12-24 1999-10-19 Purdue Pharma L.P. Orally administrable opioid formulations having extended duration of effect
US5580578A (en) 1992-01-27 1996-12-03 Euro-Celtique, S.A. Controlled release formulations coated with aqueous dispersions of acrylic polymers
US5958459A (en) 1991-12-24 1999-09-28 Purdue Pharma L.P. Opioid formulations having extended controlled released
US5286493A (en) * 1992-01-27 1994-02-15 Euroceltique, S.A. Stabilized controlled release formulations having acrylic polymer coating
US5478577A (en) 1993-11-23 1995-12-26 Euroceltique, S.A. Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level
US5472712A (en) 1991-12-24 1995-12-05 Euroceltique, S.A. Controlled-release formulations coated with aqueous dispersions of ethylcellulose
US5681585A (en) 1991-12-24 1997-10-28 Euro-Celtique, S.A. Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US5273760A (en) 1991-12-24 1993-12-28 Euroceltigue, S.A. Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
DE69216642T2 (en) 1992-01-13 1997-05-07 Pfizer METHOD FOR PRODUCING TABLETS WITH HIGH STRENGTH
US5393528A (en) * 1992-05-07 1995-02-28 Staab; Robert J. Dissolvable device for contraception or delivery of medication
US5324351A (en) 1992-08-13 1994-06-28 Euroceltique Aqueous dispersions of zein and preparation thereof
DE4227385A1 (en) 1992-08-19 1994-02-24 Kali Chemie Pharma Gmbh Pancreatin micropellets
AU682827B2 (en) * 1992-09-18 1997-10-23 Astellas Pharma Inc. Sustained-release hydrogel preparation
FI101039B (en) 1992-10-09 1998-04-15 Eeva Kristoffersson Method for preparing medicated pellets
AU679937B2 (en) 1992-11-18 1997-07-17 Johnson & Johnson Consumer Products, Inc. Extrudable compositions for topical or transdermal drug delivery
FR2701152B1 (en) 1993-02-03 1995-03-10 Digipress Sa Method for manufacturing a master disc for producing a pressing die, in particular optical discs, pressing die obtained by this process and optical disc obtained from this pressing die.
DE4309528C2 (en) 1993-03-24 1998-05-20 Doxa Gmbh Casein film or film tube, process for their production and their use
IL119660A (en) 1993-05-10 2002-09-12 Euro Celtique Sa Controlled release formulation comprising tramadol
EP0647448A1 (en) 1993-10-07 1995-04-12 Euroceltique S.A. Orally administrable opioid formulations having extended duration of effect
US5500227A (en) 1993-11-23 1996-03-19 Euro-Celtique, S.A. Immediate release tablet cores of insoluble drugs having sustained-release coating
KR100354702B1 (en) 1993-11-23 2002-12-28 유로-셀티크 소시에떼 아노뉨 Manufacturing method and sustained release composition of pharmaceutical composition
ES2168290T3 (en) 1993-11-23 2002-06-16 Euro Celtique Sa METHOD FOR PREPARING A SUSTAINED RELEASE COMPOSITION.
GB9401894D0 (en) 1994-02-01 1994-03-30 Rhone Poulenc Rorer Ltd New compositions of matter
WO1995022318A1 (en) 1994-02-17 1995-08-24 Pankaj Modi Drugs, vaccines and hormones in polylactide coated microspheres
CA2182282C (en) 1994-02-16 2006-04-18 Jacqueline E. Briskin Process for preparing fine particle pharmaceutical formulations
US5458887A (en) 1994-03-02 1995-10-17 Andrx Pharmaceuticals, Inc. Controlled release tablet formulation
JP2977907B2 (en) 1994-05-06 1999-11-15 ファイザー・インコーポレーテッド Controlled release dosage form of azithromycin
AT403988B (en) 1994-05-18 1998-07-27 Lannacher Heilmittel SOLID ORAL RETARDED PREPARATION
US5460826A (en) 1994-06-27 1995-10-24 Alza Corporation Morphine therapy
US5914131A (en) * 1994-07-07 1999-06-22 Alza Corporation Hydromorphone therapy
DE4426245A1 (en) 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-phenyl-3-dimethylamino-propane compounds with pharmacological activity
CA2130410C (en) 1994-08-18 2001-12-04 Albert John Kerklaan Retractable expandable jack
US6491945B1 (en) 1994-09-16 2002-12-10 Alza Corporation Hydrocodone therapy
US5516808A (en) 1994-10-27 1996-05-14 Sawaya; Assad S. Topical cellulose pharmaceutical formulation
US5965161A (en) * 1994-11-04 1999-10-12 Euro-Celtique, S.A. Extruded multi-particulates
DE4446470A1 (en) * 1994-12-23 1996-06-27 Basf Ag Process for the production of dividable tablets
US5585115A (en) 1995-01-09 1996-12-17 Edward H. Mendell Co., Inc. Pharmaceutical excipient having improved compressability
US5945125A (en) * 1995-02-28 1999-08-31 Temple University Controlled release tablet
US5695781A (en) 1995-03-01 1997-12-09 Hallmark Pharmaceuticals, Inc. Sustained release formulation containing three different types of polymers
US6348469B1 (en) 1995-04-14 2002-02-19 Pharma Pass Llc Solid compositions containing glipizide and polyethylene oxide
US6117453A (en) 1995-04-14 2000-09-12 Pharma Pass Solid compositions containing polyethylene oxide and an active ingredient
ATE214596T1 (en) 1995-04-14 2002-04-15 Pharma Pass SOLID COMPOSITIONS CONTAINING A NON-AMORPHOUS ACTIVE SUBSTANCE AND POLYETHYLENE OXIDE
US5654005A (en) 1995-06-07 1997-08-05 Andrx Pharmaceuticals, Inc. Controlled release formulation having a preformed passageway
US5634702A (en) 1995-09-27 1997-06-03 Fistonich; Juraj Hands free waste container having a closed cover that automatically opens when the container is moved outside its cabinet enclosure
GB9523752D0 (en) * 1995-11-21 1996-01-24 Pfizer Ltd Pharmaceutical formulations
DE19547766A1 (en) 1995-12-20 1997-06-26 Gruenenthal Gmbh 1-phenyl-2-dimethylaminomethyl-cyclohexan-1-ol compounds as active pharmaceutical ingredients
US5783212A (en) 1996-02-02 1998-07-21 Temple University--of the Commonwealth System of Higher Education Controlled release drug delivery system
ES2168610T3 (en) 1996-03-12 2002-06-16 Alza Corp COMPOSITION AND GALENIC FORM CONTAINING AN OPIOID ANTAGONIST.
US6461644B1 (en) 1996-03-25 2002-10-08 Richard R. Jackson Anesthetizing plastics, drug delivery plastics, and related medical products, systems and methods
US20020114838A1 (en) * 1996-04-05 2002-08-22 Ayer Atul D. Uniform drug delivery therapy
US6096339A (en) * 1997-04-04 2000-08-01 Alza Corporation Dosage form, process of making and using same
DE69723248T2 (en) 1996-04-10 2004-05-27 Warner-Lambert Co. Llc COMPOSITIONS FOR SYMPATHOMIMETIC AMINE SALT
US5886164A (en) * 1996-04-15 1999-03-23 Zeneca Limited DNA encoding enzymes related to ethylene biosynthesis and ripening from banana
US20040024006A1 (en) * 1996-05-06 2004-02-05 Simon David Lew Opioid pharmaceutical compositions
GB9611328D0 (en) 1996-05-31 1996-08-07 Zeneca Ltd Pharmaceutical compositions
WO1997045091A2 (en) 1996-05-31 1997-12-04 Euro-Celtique, S.A. Sustained release oxycodone formulations with no fed/fast effect
US5955096A (en) 1996-06-25 1999-09-21 Brown University Research Foundation Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients
DE09003265T1 (en) 1996-06-26 2010-04-29 Board of Regents, The University of Texas System, Austin Extrudable pharmaceutical hot melt adhesive formulation
US5730564A (en) 1996-07-24 1998-03-24 Illinois Tool Works Inc. Cargo load supporting air bag having inflation indicating means, and method of determining proper inflation for spaced loads
DE19630236A1 (en) 1996-07-26 1998-01-29 Wolff Walsrode Ag Biaxially stretched, biodegradable and compostable sausage casing
US5869669A (en) 1996-07-26 1999-02-09 Penick Corporation Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates
BE1010353A5 (en) 1996-08-14 1998-06-02 Boss Pharmaceuticals Ag Method for manufacture of pharmaceutical products, device for such a method and pharmaceutical products obtained.
JP4034357B2 (en) 1996-11-05 2008-01-16 ノバモント・ソシエタ・ペル・アチオニ Biodegradable polymer composition comprising starch and thermoplastic polymer
US6919373B1 (en) * 1996-11-12 2005-07-19 Alza Corporation Methods and devices for providing prolonged drug therapy
US5948787A (en) 1997-02-28 1999-09-07 Alza Corporation Compositions containing opiate analgesics
FR2761605B1 (en) 1997-04-07 2001-02-23 Prographarm Lab MULTIPARTICULAR PHARMACEUTICAL FORM, ITS CONSTITUENT PARTICLES, METHOD AND PLANT FOR THEIR MANUFACTURE
US6635280B2 (en) 1997-06-06 2003-10-21 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
EP0998271B3 (en) * 1997-06-06 2014-10-29 Depomed, Inc. Gastric-retentive oral drug dosage forms for controlled release of highly soluble drugs
IL121038A0 (en) 1997-06-09 1997-11-20 Technion Res & Dev Foundation A pharmaceutical composition for lowering glucose level in blood
DE19724181A1 (en) 1997-06-09 1998-12-10 Bayer Ag Multiple unit retard preparations and process for their preparation
WO1998056359A2 (en) 1997-06-13 1998-12-17 Roland Bodmeier Compounds which delay the release of active substances
GB9713703D0 (en) 1997-06-30 1997-09-03 Johnson Matthey Plc Preparation of opiates
DK1009387T3 (en) 1997-07-02 2006-08-14 Euro Celtique Sa Long-release stabilized tramadol formulations
AU739974B2 (en) * 1997-09-26 2001-10-25 Magna Interior Systems Inc. Fastener assembly for joining two interior panels
US6066339A (en) 1997-10-17 2000-05-23 Elan Corporation, Plc Oral morphine multiparticulate formulation
DE19749724A1 (en) 1997-11-11 1999-06-10 Gruenenthal Gmbh Use of a combination of opioid and alpha-adrenergic agonist in pain relievers
PT1033975E (en) * 1997-11-28 2002-07-31 Knoll Ag PROCESS FOR THE PREPARATION OF BIOLOGICALLY ACTIVE NAO-CRYSTALLINE SUBSTANCES ISSUED OF DISSOLVENTS
DE19753534A1 (en) 1997-12-03 1999-06-10 Bayer Ag Biodegradable thermoplastic polyester-amides with good mechanical properties for molding, film and fiber, useful for e.g. compostable refuse bag
GB9726365D0 (en) 1997-12-13 1998-02-11 Ciba Sc Holding Ag Compounds
PT1685839E (en) 1997-12-22 2013-07-08 Euro Celtique Sa Pharmaceutical oral dosage form comprising a combination of an opioid agonist and opioid antagonist
CA2314896C (en) * 1997-12-22 2005-09-13 Euro-Celtique, S.A. A method of preventing abuse of opioid dosage forms
NZ504834A (en) 1997-12-22 2001-12-21 Schering Corp Tricyclic amide molecular dispersion composition with enhanced bioavailability
US6375957B1 (en) * 1997-12-22 2002-04-23 Euro-Celtique, S.A. Opioid agonist/opioid antagonist/acetaminophen combinations
DE19800698A1 (en) 1998-01-10 1999-07-15 Bayer Ag Biodegradable polyester amides with block-like polyester and polyamide segments
US6251430B1 (en) * 1998-02-04 2001-06-26 Guohua Zhang Water insoluble polymer based sustained release formulation
EP0980894B1 (en) 1998-03-05 2004-06-23 Mitsui Chemicals, Inc. Polylactic acid composition and film thereof
US6245357B1 (en) 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
DE19822979A1 (en) 1998-05-25 1999-12-02 Kalle Nalo Gmbh & Co Kg Film with starch or starch derivatives and polyester urethanes and process for their production
EP0974343B1 (en) 1998-07-22 2004-09-29 Pharma Pass II LLC Process for manufacturing a solid metoprolol composition
US6117452A (en) 1998-08-12 2000-09-12 Fuisz Technologies Ltd. Fatty ester combinations
DE19855440A1 (en) 1998-12-01 2000-06-08 Basf Ag Process for the production of solid dosage forms by melt extrusion
IE981008A1 (en) 1998-12-02 2000-06-14 Fuisz Internat Ltd Microparticles Containing Water Insoluble Active Agents
EP1005863A1 (en) 1998-12-04 2000-06-07 Synthelabo Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof
US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
DE19901683B4 (en) 1999-01-18 2005-07-21 Grünenthal GmbH Controlled-release analgesic
US20030118641A1 (en) * 2000-07-27 2003-06-26 Roxane Laboratories, Inc. Abuse-resistant sustained-release opioid formulation
DE19940944B4 (en) * 1999-08-31 2006-10-12 Grünenthal GmbH Retarded, oral, pharmaceutical dosage forms
ATE279186T1 (en) 1999-08-31 2004-10-15 Gruenenthal Gmbh SUSTAINED-RELEASE PHARMACEUTICAL FORM CONTAINING TRAMADOL ACCHARINATE
US7807211B2 (en) 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
US6491683B1 (en) 1999-09-07 2002-12-10 Alza Corporation Osmotic dosage form composed of an extruded polymer tube form
US6177567B1 (en) * 1999-10-15 2001-01-23 Boehringer Ingelheim Chemicals, Inc. Method for preparing oxycodone
DE19960494A1 (en) * 1999-12-15 2001-06-21 Knoll Ag Device and method for producing solid active substance-containing forms
WO2001045644A2 (en) 1999-12-23 2001-06-28 Combe International Ltd. Dental adhesive device and method for producing same
ECSP003314A (en) 2000-01-11 2000-03-22 DELAYED DRUG FORMULATIONS CONTAINING A COMBINATION OF AN OPIOID AND AN - AGONIST
US6680070B1 (en) 2000-01-18 2004-01-20 Albemarle Corporation Particulate blends and compacted products formed therefrom, and the preparation thereof
HUP0204163A2 (en) 2000-02-08 2003-04-28 Euro-Celtique S.A. Controlled-release composition containing opioid agonist and antagonist and process for its preparation
US6277409B1 (en) * 2000-02-11 2001-08-21 Mcneil-Ppc, Inc. Protective coating for tablet
DE10015479A1 (en) 2000-03-29 2001-10-11 Basf Ag Solid oral dosage forms with delayed release of active ingredient and high mechanical stability
US20010036943A1 (en) 2000-04-07 2001-11-01 Coe Jotham W. Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines
DE10025947A1 (en) 2000-05-26 2001-11-29 Gruenenthal Gmbh Active ingredient combination containing montirelin and a compound with opioid activity
DE10025948A1 (en) 2000-05-26 2001-11-29 Gruenenthal Gmbh drug combination
EP1285902A4 (en) 2000-05-29 2007-04-18 Shionogi & Co Method for labeling with tritium
US6488962B1 (en) 2000-06-20 2002-12-03 Depomed, Inc. Tablet shapes to enhance gastric retention of swellable controlled-release oral dosage forms
DE10036400A1 (en) 2000-07-26 2002-06-06 Mitsubishi Polyester Film Gmbh White, biaxially oriented polyester film
WO2002026928A1 (en) 2000-09-28 2002-04-04 The Dow Chemical Company Polymer composite structures useful for controlled release systems
AU2738302A (en) * 2000-10-30 2002-05-15 Euro Celtique Sa Controlled release hydrocodone formulations
US20020187192A1 (en) 2001-04-30 2002-12-12 Yatindra Joshi Pharmaceutical composition which reduces or eliminates drug abuse potential
UA81224C2 (en) 2001-05-02 2007-12-25 Euro Celtic S A Dosage form of oxycodone and use thereof
US20030065002A1 (en) * 2001-05-11 2003-04-03 Endo Pharmaceuticals, Inc. Abuse-resistant controlled-release opioid dosage form
DE60216078T2 (en) * 2001-05-11 2007-07-05 Endo Pharmaceuticals Inc. OPIOID CONTAINING ARZNEIFORM AGAINST MISUSE
US20030064122A1 (en) 2001-05-23 2003-04-03 Endo Pharmaceuticals, Inc. Abuse resistant pharmaceutical composition containing capsaicin
CA2449519A1 (en) 2001-06-08 2002-12-19 Endo Pharmaceuticals, Inc. Controlled release dosage forms using acrylic polymer, and process for making the same
US7968119B2 (en) 2001-06-26 2011-06-28 Farrell John J Tamper-proof narcotic delivery system
PL207748B1 (en) * 2001-07-06 2011-01-31 Penwest Pharmaceuticals Company Sustained release formulations of oxymorphone
CA2456322A1 (en) 2001-08-06 2003-02-20 Euro-Celtique, S.A. Compositions and methods to prevent abuse of opioids
US7842307B2 (en) 2001-08-06 2010-11-30 Purdue Pharma L.P. Pharmaceutical formulation containing opioid agonist, opioid antagonist and gelling agent
US7141250B2 (en) * 2001-08-06 2006-11-28 Euro-Celtique S.A. Pharmaceutical formulation containing bittering agent
US7157103B2 (en) * 2001-08-06 2007-01-02 Euro-Celtique S.A. Pharmaceutical formulation containing irritant
US20030068375A1 (en) * 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
US7144587B2 (en) * 2001-08-06 2006-12-05 Euro-Celtique S.A. Pharmaceutical formulation containing opioid agonist, opioid antagonist and bittering agent
US7332182B2 (en) * 2001-08-06 2008-02-19 Purdue Pharma L.P. Pharmaceutical formulation containing opioid agonist, opioid antagonist and irritant
WO2003015531A2 (en) 2001-08-06 2003-02-27 Thomas Gruber Pharmaceutical formulation containing dye
CA2455420A1 (en) 2001-08-06 2003-02-20 Euro-Celtique, S.A. Compositions and methods to prevent abuse of opioids
US20030069318A1 (en) * 2001-08-21 2003-04-10 Wenbin Dang Salts of analgesic substances in oil, and methods of making and using the same
US6691698B2 (en) 2001-09-14 2004-02-17 Fmc Technologies Inc. Cooking oven having curved heat exchanger
US20030068276A1 (en) 2001-09-17 2003-04-10 Lyn Hughes Dosage forms
US20030092724A1 (en) 2001-09-18 2003-05-15 Huaihung Kao Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic
US20040253310A1 (en) * 2001-09-21 2004-12-16 Gina Fischer Morphine polymer release system
US20040234602A1 (en) 2001-09-21 2004-11-25 Gina Fischer Polymer release system
EP1429735A2 (en) 2001-09-26 2004-06-23 Klaus-Jürgen Steffens Method and device for producing granulates that comprise at least one pharmaceutical active substance
JP2005508325A (en) 2001-09-28 2005-03-31 マクニール−ピーピーシー・インコーポレイテッド Dosage form having an inner core and an outer shell
US20030229158A1 (en) 2001-09-28 2003-12-11 Chen Jen Chi Polymer composition and dosage forms comprising the same
US6982094B2 (en) 2001-09-28 2006-01-03 Mcneil-Ppc, Inc. Systems, methods and apparatuses for manufacturing dosage forms
PE20030527A1 (en) 2001-10-24 2003-07-26 Gruenenthal Chemie DELAYED-RELEASE PHARMACEUTICAL FORMULATION CONTAINING 3- (3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL) PHENOL OR A PHARMACEUTICALLY ACCEPTABLE SALT OF THE SAME AND ORAL TABLETS CONTAINING IT
US20030152622A1 (en) * 2001-10-25 2003-08-14 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral diuretic
US20030104052A1 (en) * 2001-10-25 2003-06-05 Bret Berner Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
US6723340B2 (en) * 2001-10-25 2004-04-20 Depomed, Inc. Optimal polymer mixtures for gastric retentive tablets
CA2409552A1 (en) 2001-10-25 2003-04-25 Depomed, Inc. Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
US20030091630A1 (en) * 2001-10-25 2003-05-15 Jenny Louie-Helm Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data
US20040126428A1 (en) * 2001-11-02 2004-07-01 Lyn Hughes Pharmaceutical formulation including a resinate and an aversive agent
FR2833838B1 (en) 2001-12-21 2005-09-16 Ellipse Pharmaceuticals METHOD FOR MANUFACTURING A TABLET INCLUDING A MORPHINIC ANALGESIC AND TABLET OBTAINED
US20030161882A1 (en) * 2002-02-01 2003-08-28 Waterman Kenneth C. Osmotic delivery system
DK1476138T3 (en) 2002-02-21 2012-02-20 Valeant Internat Barbados Srl Modified release formulations of at least one form of tramadol
GB0204772D0 (en) 2002-02-28 2002-04-17 Phoqus Ltd Pharmaceutical dosage forms
DE10217232B4 (en) * 2002-04-18 2004-08-19 Ticona Gmbh Process for the production of filled granules from polyethylene of high or ultra-high molecular weight
US20050106249A1 (en) * 2002-04-29 2005-05-19 Stephen Hwang Once-a-day, oral, controlled-release, oxycodone dosage forms
CN1665482A (en) * 2002-04-29 2005-09-07 阿尔扎公司 Methods and dosage forms for controlled delivery of oxycodone
AU2003234395B2 (en) 2002-05-13 2008-01-24 Endo Pharmaceuticals Inc. Abuse-resistant opioid solid dosage form
WO2003097608A2 (en) * 2002-05-17 2003-11-27 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
WO2003101384A2 (en) 2002-05-31 2003-12-11 Alza Corporation Dosage forms and compositions for osmotic delivery of variable dosages of oxycodone
US7776314B2 (en) * 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
DE10250083A1 (en) 2002-06-17 2003-12-24 Gruenenthal Gmbh Dosage form protected against abuse
CA2491572C (en) * 2002-07-05 2010-03-23 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opiods and other drugs
US20040011806A1 (en) * 2002-07-17 2004-01-22 Luciano Packaging Technologies, Inc. Tablet filler device with star wheel
JP2005538105A (en) 2002-07-25 2005-12-15 ファルマシア・コーポレーション Method for producing a solid dosage form coated with two layers comprising a water-insoluble polymer and a water-soluble pore-forming substance
CA2495182A1 (en) 2002-08-15 2004-02-26 Noramco, Inc. Oxycodone-hydrochloride polymorphs
EP1539098B1 (en) 2002-09-20 2011-08-10 Fmc Corporation Cosmetic composition containing microcrystalline cellulose
CA2499994C (en) 2002-09-23 2012-07-10 Verion, Inc. Abuse-resistant pharmaceutical compositions
BR0314787A (en) * 2002-09-28 2005-07-26 Mcneil Ppc Inc Modified Release Dosage Form
DE10250088A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
DE10250084A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
DE10250087A1 (en) 2002-10-25 2004-05-06 Grünenthal GmbH Dosage form protected against abuse
US8487002B2 (en) 2002-10-25 2013-07-16 Paladin Labs Inc. Controlled-release compositions
US20040110781A1 (en) 2002-12-05 2004-06-10 Harmon Troy M. Pharmaceutical compositions containing indistinguishable drug components
US20040185097A1 (en) 2003-01-31 2004-09-23 Glenmark Pharmaceuticals Ltd. Controlled release modifying complex and pharmaceutical compositions thereof
CA2519556C (en) 2003-04-21 2011-01-18 Benjamin Oshlack Tamper resistant dosage form comprising co-extruded, adverse agent particles and process of making same
CL2004000927A1 (en) 2003-04-30 2005-01-28 Purdue Pharma Lp TRANSDERMAL DOSAGE FORM THAT INCLUDES AN ACTIVE AGENT, A NEXT SURFACE AND A DISTAL SURFACE.
US20060251724A1 (en) 2003-05-06 2006-11-09 Farrell Thomas P Method for preparing thermoformed compositions containing acrylic polymer binders, pharmaceutical dosage forms and methods of preparing the same
US20040241234A1 (en) 2003-06-02 2004-12-02 Alpharma, Inc. Controlled release press-coated formulations of water-soluble active agents
US6864370B1 (en) * 2003-06-05 2005-03-08 Zhaiwei Lin Process for manufacturing oxycodone
TWI357815B (en) 2003-06-27 2012-02-11 Euro Celtique Sa Multiparticulates
US20050031655A1 (en) 2003-08-04 2005-02-10 Schering Plough Healthcare Products, Inc. Emulsion composition
DE102004020220A1 (en) 2004-04-22 2005-11-10 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
DE10336400A1 (en) 2003-08-06 2005-03-24 Grünenthal GmbH Anti-abuse dosage form
CA2534925A1 (en) * 2003-08-06 2005-02-24 Gruenenthal Gmbh Dosage form that is safeguarded from abuse
DE10361596A1 (en) * 2003-12-24 2005-09-29 Grünenthal GmbH Process for producing an anti-abuse dosage form
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
DE102004032051A1 (en) * 2004-07-01 2006-01-19 Grünenthal GmbH Process for the preparation of a secured against misuse, solid dosage form
US20070048228A1 (en) * 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE102005005446A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Break-resistant dosage forms with sustained release
US20050089570A1 (en) * 2003-09-26 2005-04-28 Evangeline Cruz Oros push-stick for controlled delivery of active agents
CA2541371C (en) 2003-10-03 2014-12-16 Atul M. Mehta Extended release formulations of opioids and method of use thereof
EP1677798A2 (en) 2003-10-29 2006-07-12 Alza Corporation Once-a-day, oral, controlled-release, oxycodone dosage forms
US7201920B2 (en) 2003-11-26 2007-04-10 Acura Pharmaceuticals, Inc. Methods and compositions for deterring abuse of opioid containing dosage forms
WO2005070760A1 (en) 2004-01-23 2005-08-04 Antoine Sakellarides Shock absorbing system for rowing boat oarlock
WO2005079752A2 (en) 2004-02-11 2005-09-01 Rubicon Research Private Limited Controlled release pharmaceutical compositions with improved bioavailability
TWI350762B (en) 2004-02-12 2011-10-21 Euro Celtique Sa Particulates
TW201509943A (en) * 2004-03-30 2015-03-16 Euro Celtique Sa Oxycodone hydrochloride composition, pharmaceutical dosage form, sustained release oral dosage form and pharmaceutically acceptable package having less than 25 PPM 14-hydroxycodeinone
WO2005102286A1 (en) * 2004-04-22 2005-11-03 Grünenthal GmbH Method for the production of an abuse-proof, solid form of administration
JP2006002886A (en) * 2004-06-18 2006-01-05 Noriatsu Kojima Drain pipe
JP2006002884A (en) * 2004-06-18 2006-01-05 Mitsubishi Plastics Ind Ltd Connector
WO2006002286A1 (en) * 2004-06-22 2006-01-05 Magna International Inc. Sealing molding for a motor vehicle
PL1765303T5 (en) 2004-07-01 2023-05-22 Grünenthal GmbH Oral dosage form safeguarded against abuse
AR049839A1 (en) 2004-07-01 2006-09-06 Gruenenthal Gmbh PROCEDURE FOR THE PRODUCTION OF A SOLID PHARMACEUTICAL FORM, PROTECTED AGAINST ABUSE
DE102004032049A1 (en) 2004-07-01 2006-01-19 Grünenthal GmbH Anti-abuse, oral dosage form
AR053304A1 (en) 2004-07-01 2007-05-02 Gruenenthal Gmbh PROTECTED ORAL PHARMACEUTICAL FORMS AGAINST ABUSE WITH CONTROLLED RELEASE OF (1R, 2R) -3- (3 DIMETHYLAMIN-1-ETIL-2METIL-PROPIL) PHENOL AND PROCEDURE FOR PRODUCTION.
GB0421149D0 (en) 2004-09-23 2004-10-27 Johnson Matthey Plc Preparation of oxycodone
MX2007009162A (en) 2005-01-28 2007-10-23 Euro Celtique Sa Alcohol resistant dosage forms.
DE102005005449A1 (en) 2005-02-04 2006-08-10 Grünenthal GmbH Process for producing an anti-abuse dosage form
US20080274183A1 (en) 2005-02-04 2008-11-06 Phillip Michael Cook Thermoplastic articles containing a medicament
US7732427B2 (en) 2005-03-31 2010-06-08 University Of Delaware Multifunctional and biologically active matrices from multicomponent polymeric solutions
BRPI0612802A2 (en) * 2005-07-07 2010-11-30 Farnam Co Inc sustained release pharmaceutical compositions for extremely water soluble drugs
US20070092573A1 (en) 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
PL116330U1 (en) 2005-10-31 2007-04-02 Alza Corp Method for the reduction of alcohol provoked rapid increase in the released dose of the orally administered opioide with prolonged liberation
US20070117826A1 (en) * 2005-11-23 2007-05-24 Forest Laboratories, Inc. Pharmaceutical formulations comprising ibuprofen, oxycodone, and 14-hydroxycodeinone
US20090022798A1 (en) 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
US20070212414A1 (en) 2006-03-08 2007-09-13 Penwest Pharmaceuticals Co. Ethanol-resistant sustained release formulations
US7778314B2 (en) 2006-05-04 2010-08-17 Texas Instruments Incorporated Apparatus for and method of far-end crosstalk (FEXT) detection and estimation
SA07280459B1 (en) * 2006-08-25 2011-07-20 بيورديو فارما إل. بي. Tamper Resistant Oral Pharmaceutical Dosage Forms Comprising an Opioid Analgesic
EP2121699B1 (en) 2006-12-04 2012-09-19 Noramco, Inc. Process for preparing oxycodone having reduced levels of 14-hydroxycodeinone
PE20081632A1 (en) 2007-01-12 2008-12-10 Wyeth Corp TABLET TO TABLET COMPOSITIONS
EP2104493A2 (en) 2007-01-16 2009-09-30 Egalet A/S Use of i) a polyglycol and n) an active drug substance for the preparation of a pharmaceutical composition for i) mitigating the risk of alcohol induced dose dumping and/or ii) reducing the risk of drug abuse
GB2450691A (en) 2007-07-02 2009-01-07 Alpharma Aps One-pot preparation of oxycodone from thebaine
EP2262484B1 (en) 2008-03-11 2013-01-23 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US8671872B2 (en) 2009-02-16 2014-03-18 Thomas Engineering Inc. Production coater with exchangeable drums
KR101738369B1 (en) * 2009-07-22 2017-05-22 그뤼넨탈 게엠베하 Hot-melt extruded controlled release dosage form
US9492492B2 (en) * 2010-12-17 2016-11-15 Johnson & Johnson Consumer Inc. Compositions comprising Lilium martagon extracts and uses thereof
EP2826468A1 (en) * 2010-12-22 2015-01-21 Purdue Pharma L.P. Encased tamper resistant controlled release dosage forms
US9846413B2 (en) * 2011-09-08 2017-12-19 Fire Avert, Llc. Safety shut-off device and method of use
US10764498B2 (en) * 2017-03-22 2020-09-01 Canon Kabushiki Kaisha Image processing apparatus, method of controlling the same, and storage medium
US10764499B2 (en) * 2017-06-16 2020-09-01 Microsoft Technology Licensing, Llc Motion blur detection

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114659554A (en) * 2022-03-01 2022-06-24 安徽农业大学 Fault diagnosis method for biomass granulator
CN114659554B (en) * 2022-03-01 2023-04-25 安徽农业大学 Fault diagnosis method for biomass granulator

Also Published As

Publication number Publication date
US8846086B2 (en) 2014-09-30
PT2082742E (en) 2011-03-02
DK2399579T3 (en) 2013-06-17
IL217790A0 (en) 2012-03-29
HRP20130433T1 (en) 2013-06-30
MA30766B1 (en) 2009-10-01
US20170319489A1 (en) 2017-11-09
US20140024669A1 (en) 2014-01-23
CN102657630B (en) 2014-10-01
US20170319492A1 (en) 2017-11-09
KR20090045381A (en) 2009-05-07
JP5373133B2 (en) 2013-12-18
IN2015DN01813A (en) 2015-07-10
JP2012167102A (en) 2012-09-06
US20170348240A1 (en) 2017-12-07
DK2292230T3 (en) 2012-08-20
KR101455914B1 (en) 2014-11-03
CY1113141T1 (en) 2016-04-13
CN102657630A (en) 2012-09-12
JP2010501543A (en) 2010-01-21
ME01255B (en) 2013-06-20
US20170319493A1 (en) 2017-11-09
US9492389B2 (en) 2016-11-15
EP2292230B1 (en) 2012-05-23
KR101514388B1 (en) 2015-04-23
PT2292229E (en) 2012-08-28
RS52793B (en) 2013-10-31
MY161079A (en) 2017-04-14
NZ597760A (en) 2013-04-26
US20170319497A1 (en) 2017-11-09
US9492393B2 (en) 2016-11-15
SI1897545T1 (en) 2010-01-29
US9492391B2 (en) 2016-11-15
HK1154491A1 (en) 2012-04-27
EP1897545B1 (en) 2009-09-30
SI2292229T1 (en) 2012-09-28
US9763886B2 (en) 2017-09-19
US11304909B2 (en) 2022-04-19
US20130251798A1 (en) 2013-09-26
KR101568100B1 (en) 2015-11-12
US20150265601A1 (en) 2015-09-24
AT11571U1 (en) 2011-01-15
RS52779B (en) 2013-10-31
KR20170118249A (en) 2017-10-24
EP2080514A1 (en) 2009-07-22
US9095614B2 (en) 2015-08-04
DK2343071T3 (en) 2013-05-13
ES2411696T3 (en) 2013-07-08
ATE499101T1 (en) 2011-03-15
CN102743355B (en) 2014-12-24
HK1165316A1 (en) 2012-10-05
EP2082742A1 (en) 2009-07-29
EA031873B1 (en) 2019-03-29
PT2399579E (en) 2013-06-24
CL2007002485A1 (en) 2008-01-25
BR122016004010B1 (en) 2020-11-24
EP2311459A1 (en) 2011-04-20
CY1113231T1 (en) 2016-04-13
US8808741B2 (en) 2014-08-19
JP5642736B2 (en) 2014-12-17
CL2017000669A1 (en) 2017-11-10
US11938225B2 (en) 2024-03-26
CY1111896T1 (en) 2015-11-04
US20130259939A1 (en) 2013-10-03
CY1111887T1 (en) 2015-11-04
US20170128370A1 (en) 2017-05-11
JP2012236835A (en) 2012-12-06
US20230134700A1 (en) 2023-05-04
US9095615B2 (en) 2015-08-04
US8834925B2 (en) 2014-09-16
KR101649838B1 (en) 2016-08-19
ES2390419T3 (en) 2012-11-12
US20190000767A1 (en) 2019-01-03
EP2399579A1 (en) 2011-12-28
CA2707204A1 (en) 2008-02-28
EA200900343A1 (en) 2009-08-28
AR062511A1 (en) 2008-11-12
HK1154788A1 (en) 2012-05-04
US20150335582A1 (en) 2015-11-26
US9775812B2 (en) 2017-10-03
KR20120105566A (en) 2012-09-25
IL217792A (en) 2015-09-24
ME01339B (en) 2013-12-20
CN103861111B (en) 2017-04-12
EP2082742B1 (en) 2010-12-01
EA201300465A1 (en) 2013-08-30
KR101205579B1 (en) 2012-11-28
US20130259938A1 (en) 2013-10-03
UA96306C2 (en) 2011-10-25
US8821929B2 (en) 2014-09-02
GT200900023BA (en) 2018-09-28
US11826472B2 (en) 2023-11-28
HRP20130434T1 (en) 2013-06-30
US20150265600A1 (en) 2015-09-24
PL2399579T3 (en) 2013-12-31
DE602007012747D1 (en) 2011-04-07
US8815289B2 (en) 2014-08-26
US20170128374A1 (en) 2017-05-11
US20150335585A1 (en) 2015-11-26
IL241121A (en) 2017-09-28
CN105213345B (en) 2019-04-19
US20130251799A1 (en) 2013-09-26
US9492390B2 (en) 2016-11-15
US20170319488A1 (en) 2017-11-09
EP2292230A1 (en) 2011-03-09
JP2012229249A (en) 2012-11-22
JP2012229250A (en) 2012-11-22
DK2070538T3 (en) 2011-03-21
MY153092A (en) 2014-12-31
PL2384754T3 (en) 2013-12-31
EP2399580B1 (en) 2013-04-03
US20150028512A1 (en) 2015-01-29
AU2007287341B2 (en) 2011-08-25
SI2399580T1 (en) 2013-07-31
CN103861111A (en) 2014-06-18
CN105213345A (en) 2016-01-06
HK1156845A1 (en) 2012-06-22
US10076499B2 (en) 2018-09-18
RS52463B (en) 2013-02-28
US20130260015A1 (en) 2013-10-03
RS52798B (en) 2013-10-31
HRP20120641T1 (en) 2012-08-31
US8911719B2 (en) 2014-12-16
US20170128369A1 (en) 2017-05-11
ES2411695T3 (en) 2013-07-08
DOP2009000026A (en) 2009-07-15
CY1113220T1 (en) 2016-04-13
PT2343071E (en) 2013-05-29
SI2292230T1 (en) 2012-09-28
US9763933B2 (en) 2017-09-19
US20150037411A1 (en) 2015-02-05
PT2384754E (en) 2013-05-24
MX2009002023A (en) 2009-03-05
PT2080514E (en) 2011-05-24
US20210000747A1 (en) 2021-01-07
CO6160317A2 (en) 2010-05-20
AP2009004770A0 (en) 2009-02-28
BR122016004010B8 (en) 2021-05-25
US20140031381A1 (en) 2014-01-30
GT200900023A (en) 2010-11-05
US9770417B2 (en) 2017-09-26
JO2858B1 (en) 2015-03-15
US20170319498A1 (en) 2017-11-09
DK1897545T3 (en) 2010-02-08
ES2361721T3 (en) 2011-06-21
RS51591B (en) 2011-08-31
HRP20130444T1 (en) 2013-06-30
RS52813B (en) 2013-10-31
PT1897545E (en) 2009-12-16
NZ574447A (en) 2012-04-27
HK1138498A1 (en) 2010-08-27
KR101496510B1 (en) 2015-03-03
CN102688213A (en) 2012-09-26
IL241122B (en) 2019-05-30
IL241122A0 (en) 2015-11-30
TWI341213B (en) 2011-05-01
EA023807B1 (en) 2016-07-29
US20130251800A1 (en) 2013-09-26
ATE489954T1 (en) 2010-12-15
PT2292230E (en) 2012-08-28
EP2399580A1 (en) 2011-12-28
CR10691A (en) 2009-06-05
EP1897545A1 (en) 2008-03-12
US9775809B2 (en) 2017-10-03
US9101661B2 (en) 2015-08-11
EA018311B1 (en) 2013-07-30
JP2016222698A (en) 2016-12-28
US20170246116A1 (en) 2017-08-31
US20130251801A1 (en) 2013-09-26
US20170128375A1 (en) 2017-05-11
KR20140049085A (en) 2014-04-24
ES2417334T3 (en) 2013-08-07
IL197214A (en) 2015-09-24
IL241121A0 (en) 2015-11-30
PL2080514T3 (en) 2011-09-30
DK2399580T3 (en) 2013-06-24
HRP20090688T1 (en) 2010-02-28
ATE444070T1 (en) 2009-10-15
CN107412179B (en) 2020-09-04
US20150037412A1 (en) 2015-02-05
CR20140340A (en) 2014-10-16
EP2384754B1 (en) 2013-03-20
ES2334466T3 (en) 2010-03-10
US9770416B2 (en) 2017-09-26
IL217788A0 (en) 2012-03-29
IL217791A (en) 2015-09-24
PE20150340A1 (en) 2015-02-28
JP5980881B2 (en) 2016-08-31
SI2399579T1 (en) 2013-07-31
US20130251796A1 (en) 2013-09-26
KR101787605B1 (en) 2017-10-19
DE602007002596D1 (en) 2009-11-12
DE602007010974D1 (en) 2011-01-13
PE20140854A1 (en) 2014-07-19
RS51678B (en) 2011-10-31
AR109797A2 (en) 2019-01-23
DK2311459T3 (en) 2012-09-10
TW200824722A (en) 2008-06-16
US20130251802A1 (en) 2013-09-26
ZA200900755B (en) 2009-12-30
DK2080514T3 (en) 2011-05-16
SI2311459T1 (en) 2012-10-30
US20180153814A1 (en) 2018-06-07
SI2082742T1 (en) 2011-03-31
ME01064B (en) 2012-10-20
US20170319490A1 (en) 2017-11-09
IL217792A0 (en) 2012-03-29
US9545380B2 (en) 2017-01-17
AU2007287341A1 (en) 2008-02-28
US20210000748A1 (en) 2021-01-07
KR20120105565A (en) 2012-09-25
PT2070538E (en) 2011-03-02
SI2384754T1 (en) 2013-07-31
IL197214A0 (en) 2009-12-24
SI2343071T1 (en) 2013-07-31
IL217787A0 (en) 2012-03-29
EP2384754A1 (en) 2011-11-09
EP2311459B1 (en) 2012-06-27
HRP20120613T1 (en) 2012-08-31
US20170319494A1 (en) 2017-11-09
PE20191048A1 (en) 2019-08-06
US9486412B2 (en) 2016-11-08
US9084816B2 (en) 2015-07-21
SA07280459B1 (en) 2011-07-20
EP2343071B1 (en) 2013-03-20
PL2292230T3 (en) 2012-10-31
US20150037413A1 (en) 2015-02-05
ES2357376T3 (en) 2011-04-25
UA104745C2 (en) 2014-03-11
US20150265599A1 (en) 2015-09-24
US9486413B2 (en) 2016-11-08
BRPI0714539B1 (en) 2020-11-24
IL217794A0 (en) 2012-03-29
DE602007010963D1 (en) 2011-01-13
ES2388591T3 (en) 2012-10-16
DK2292229T3 (en) 2012-08-13
HRP20110147T1 (en) 2011-04-30
US8894988B2 (en) 2014-11-25
EP2343071A1 (en) 2011-07-13
US20170128373A1 (en) 2017-05-11
CN102688241A (en) 2012-09-26
US8894987B2 (en) 2014-11-25
EP2070538A1 (en) 2009-06-17
BRPI0714539A2 (en) 2014-02-25
HRP20120670T1 (en) 2012-09-30
CY1110573T1 (en) 2015-04-29
JO3323B1 (en) 2019-03-13
EP2292229B1 (en) 2012-05-23
US20230270684A1 (en) 2023-08-31
KR20150082669A (en) 2015-07-15
ME01187B (en) 2011-10-31
US9492392B2 (en) 2016-11-15
KR20110119847A (en) 2011-11-02
ES2417335T3 (en) 2013-08-07
RS52401B (en) 2013-02-28
CN105267170B (en) 2019-01-01
HRP20110130T1 (en) 2011-03-31
PE20091184A1 (en) 2009-08-03
HRP20110375T1 (en) 2011-06-30
HK1133192A1 (en) 2010-03-19
PL2082742T3 (en) 2011-05-31
CN101583360A (en) 2009-11-18
TN2009000059A1 (en) 2010-08-19
US20150335583A1 (en) 2015-11-26
EP2070538B1 (en) 2010-12-01
EP2292229A1 (en) 2011-03-09
PT2399580E (en) 2013-07-05
US20170319495A1 (en) 2017-11-09
US20090081290A1 (en) 2009-03-26
US20170065527A1 (en) 2017-03-09
IL217789A0 (en) 2012-03-29
EA201171403A1 (en) 2012-05-30
RS52402B (en) 2013-02-28
JP6286491B2 (en) 2018-02-28
HK1165318A1 (en) 2012-10-05
US20180369150A1 (en) 2018-12-27
BRPI0714539B8 (en) 2021-05-25
ATE489953T1 (en) 2010-12-15
ME01482B (en) 2014-04-20
US20150335584A1 (en) 2015-11-26
US20170128372A1 (en) 2017-05-11
PL2399580T3 (en) 2013-12-31
WO2008023261A1 (en) 2008-02-28
US10076498B2 (en) 2018-09-18
US20170319491A1 (en) 2017-11-09
DK2384754T3 (en) 2013-05-06
HK1132189A1 (en) 2010-02-19
PL2343071T3 (en) 2013-12-31
US11298322B2 (en) 2022-04-12
JP5069300B2 (en) 2012-11-07
CL2014001029A1 (en) 2014-09-12
CN101583360B (en) 2014-02-26
SI2080514T1 (en) 2011-05-31
US20170319496A1 (en) 2017-11-09
KR20160099738A (en) 2016-08-22
PL1897545T3 (en) 2010-02-26
US9775810B2 (en) 2017-10-03
US20210169810A1 (en) 2021-06-10
US11904055B2 (en) 2024-02-20
CA2707204C (en) 2015-06-23
CY1111897T1 (en) 2015-11-04
AR103463A2 (en) 2017-05-10
SI2070538T1 (en) 2011-03-31
CN105267170A (en) 2016-01-27
EP2080514B1 (en) 2011-02-23
US20170128371A1 (en) 2017-05-11
EP2399579B1 (en) 2013-04-03
US20170354607A1 (en) 2017-12-14
DE202007011825U1 (en) 2008-04-30
PL2311459T3 (en) 2012-12-31
CN102688241B (en) 2017-04-12
US9775808B2 (en) 2017-10-03
PL2292229T3 (en) 2012-10-31
US20140030327A1 (en) 2014-01-30
US20230310326A1 (en) 2023-10-05
HK1246175A1 (en) 2018-09-07
HK1165317A1 (en) 2012-10-05
DOP2011000255A (en) 2011-10-15
US9775811B2 (en) 2017-10-03
US20130259940A1 (en) 2013-10-03
AR109796A2 (en) 2019-01-23
IL217791A0 (en) 2012-03-29
HRP20130539T1 (en) 2013-07-31
US20170128440A1 (en) 2017-05-11
RS51664B (en) 2011-10-31
PE20080765A1 (en) 2008-06-13
NZ608651A (en) 2014-07-25
US11304908B2 (en) 2022-04-19
MX360849B (en) 2018-11-20
US20130251797A1 (en) 2013-09-26
RS51162B (en) 2010-10-31
IL217794A (en) 2015-09-24
US20150335580A1 (en) 2015-11-26
EP2399579B9 (en) 2013-07-24
ES2358066T3 (en) 2011-05-05
HK1154789A1 (en) 2012-05-04
JP2015044834A (en) 2015-03-12
PL2070538T3 (en) 2011-05-31
DK2082742T3 (en) 2011-03-21
JP2012136543A (en) 2012-07-19
HK1118225A1 (en) 2009-02-06
CN102743355A (en) 2012-10-24
CN107412179A (en) 2017-12-01
US20180153815A1 (en) 2018-06-07
US20210000749A1 (en) 2021-01-07
CA2661573C (en) 2010-10-26
ME01580B (en) 2014-09-20
US20170348241A1 (en) 2017-12-07
MY146650A (en) 2012-09-14
PT2311459E (en) 2012-09-26
ME01550B (en) 2014-04-20
ES2388615T3 (en) 2012-10-17

Similar Documents

Publication Publication Date Title
CA2661573A1 (en) Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic
CA2913368C (en) Abuse deterrent immediate release formulation
HRP20150835T1 (en) Controlled release pharmaceutical dosage forms
AU2011346758B2 (en) Tamper resistant solid oral dosage forms
AU2005282784B2 (en) Opioid dosage forms having dose proportional steady state Cave and AUC and less than dose proportional single dose Cmax
JP2006524249A5 (en)
CA2652981A1 (en) Robust sustained release formulations
CA2640339A1 (en) Tamper resistant opioid dosage forms
HRP20100289T1 (en) Tamper-resistant products for opioid delivery
JP2014510094A5 (en)
JP2010501543A5 (en)
RU2011121010A (en) PHARMACEUTICAL MEDICINAL FORMS CONTAINING POLY- (Epsilon-caprolactone)
KR20090038447A (en) Multilayer orally disintegrating tablet
JP2008528534A5 (en)
EP2768537A2 (en) Acrylic polymer formulations
AU2017241266B2 (en) Extended release, abuse deterrent dosage forms
RU2017112301A (en) PHARMACEUTICAL COMPOSITIONS RESISTANT TO ABUSE
WO2016120892A1 (en) Abuse deterrent controlled release solid dosage form
HRP20141001T1 (en) Pharmaceutical spheroids
JP7293209B2 (en) Pharmaceutical dosage form
US10624856B2 (en) Non-extractable oral solid dosage forms
JP2021500316A5 (en)
US11439600B2 (en) Abuse deterrent oral solid dosage form
WO2019152002A1 (en) Non-extractable oral solid dosage forms
AU2011202866B2 (en) Tamper resistant dosage forms

Legal Events

Date Code Title Description
EEER Examination request